Transformer-Based Weakly Supervised Learning for Whole Slide Lung Cancer Image Classification.

Image analysis can play an important role in supporting histopathological diagnoses of lung cancer, with deep learning methods already achieving remarkable results. However, due to the large scale of whole-slide images (WSIs), creating manual pixel-wise annotations from expert pathologists is expensive and time-consuming. In addition, the heterogeneity of tumors and similarities in the morphological phenotype of tumor subtypes have caused inter-observer variability in annotations, which limits optimal performance. Effective use of weak labels could potentially alleviate these issues. In this paper, we propose a two-stage transformer-based weakly supervised learning framework called Simple Shuffle-Remix Vision Transformer (SSRViT). Firstly, we introduce a Shuffle-Remix Vision Transformer (SRViT) to retrieve discriminative local tokens and extract effective representative features. Then, the token features are selected and aggregated to generate sparse representations of WSIs, which are fed into a simple transformer-based classifier (SViT) for slide-level prediction. Experimental results demonstrate that the performance of our proposed SSRViT is significantly improved compared with other state-of-the-art methods in discriminating between adenocarcinoma, pulmonary sclerosing pneumocytoma and normal lung tissue (accuracy of 96.9% and AUC of 99.6%).

Tong-Xie-Yao-Fang Induces Mitophagy in Colonic Epithelial Cells to Inhibit Colitis-associated Colorectal Cancer.

ETHNOPHARMACOLOGICAL RELEVANCE: Based on the core pathogenesis of hepatosplenic disorder and qi transformation disorder in ulcerative colitis, Tong-Xie-Yao-Fang (TXYF) is a classical traditional Chinese medicine commonly used to treat ulcerative colitis. Our study revealed that it has the potential to prevent colitis-associated colorectal cancer, which embodies the academic concept in traditional Chinese medicine of treating the disease before it develops. AIM OF THE STUDY: This study was aimed at evaluating the therapeutic role of TXYF in treating colitis-associated colorectal cancer and exploring its possible underlying mechanisms. MATERIALS AND METHODS: A colitis-associated colorectal cancer model was established in mice using azoxymethane and dextran sulfate sodium salt to examine the therapeutic effect of TXYF. The mouse body weights were observed. Hematoxylin-eosin staining was used to evaluate mouse colon histopathology. Colon cancer cells and colon epithelial cells were used to explore the potential molecular mechanisms. The proliferation and apoptosis of cells were detected by CCK-8 and cell colony assays, flow cytometry and western blotting. The epithelial-mesenchymal transition (EMT) and mitophagy markers were examined by immunohistochemistry, western blotting, quantitative real-time PCR and immunofluorescence staining. RESULTS: TXYF inhibited the tumorigenesis of mice with colitis-associated colorectal cancer and the growth of inflammatory colon cells. TXYF induced mitophagy in colon cancer cells through the PTEN-induced putative kinase 1 (PINK1)/Parkin pathway to reverse EMT, which was consistent with the results in mice with colitis-associated colorectal cancer. CONCLUSIONS: The results of the present study demonstrated that TXYF effectively inhibited the progression of colitis-associated colorectal cancer through the PINK1/Parkin pathway, which provides new evidence for prevention strategies for this disease.

On-chip omnidirectional electromagnetic-thermal cloak.

Simultaneously guiding electromagnetic waves and heat flow at any incidence angle to smoothly bypass some electromagnetic/thermal sensitive elements is a key factor to ensure efficient communication and thermal protection for an on-chip system. In this study, an omnidirectional on-chip electromagnetic-thermal cloak is proposed. Firstly, a holey metallic plate with periodic array of subwavelength apertures is designed by optical surface transformation to realize an omnidirectional electromagnetic cloaking module for on-chip electromagnetic signal. Secondly, a two-layer ring-shaped engineered thermal structure is designed by solving Laplace equation to realize an omnidirectional thermal cloaking module for in-chip heat flow. Finally, these two cloaking modules are combined to achieve cloaking effect for both the electromagnetic waves and thermal fields simultaneously, thus protecting the build-in electromagnetic/thermal sensitive elements without disturbing the external fields. The proposed electromagnetic-thermal cloak may have potential advantage in dealing with omnidirectional electromagnetic compatibility/shielding and multi-directional thermal management/dissipation of an on-chip system.

Biomechanical Analysis of Transosseous Repair Versus Combined Transosseous With Capsular Repair for Triangular Fibrocartilage Complex Tears With Instability.

PURPOSE: This study compared the biomechanical stability of transosseous repair and transosseous combined with capsular repair techniques to reattach the triangular fibrocartilage complex (TFCC) for distal radioulnar joint instability. METHODS: Eight adult cadaveric upper-extremity specimens were studied. Each underwent peripheral ulnar-sided detachment of the deep and superficial TFCC fibers and repair. Four groups were prepared sequentially: intact TFCC, disrupted TFCC, transosseous repair, and combined transosseous with capsular repair. Forearm rotational torque was measured in three wrist positions: 60° flexion, neutral position, and 60° extension. Maximum dorsal and palmar ulnar translations in response to a 20-N traction load were measured at nine wrist positions after stabilizing the humerus and radius. Measurements were taken before and after TFCC disruption and following repair. RESULTS: Clear instability of the radius relative to the ulna was observed after sectioning the deep and superficial fibers of the TFCC, and stability was markedly improved after reconstruction in all positions. Compared with the normal group, rotational torque was similar between the two repair methods. In the pronation palmar flexion and supination dorsal extension positions, dorsal-palmar translation was smaller in the combined transosseous with capsular repair group than in the transosseous repair-alone group. CONCLUSIONS: Triangular fibrocartilage complex deep fibers are the primary stabilizing structure of the distal radioulnar joint. In this cadaveric study, the combined transosseous with capsular repair technique demonstrated less dorsal-palmar translation compared with the transosseous-alone repair technique. CLINICAL RELEVANCE: Combined transosseous with capsular repair is expected to provide improved postoperative stability for patients with peripheral TFCC tears and distal radioulnar joint instability.

A Rare Case of Iliac Saccular Aneurysm Communicating with a Transplant Renal Artery.

BACKGROUND Isolated iliac aneurysms are rare. Although they grow very slowly, they can rupture when large enough. Rarely, they rupture into an adjacent organ, such as the colon, the bladder, or even an adjacent vein. Cases of aneurysms rupturing into or communicating with an adjacent vein, leading to an arteriovenous fistula, have been reported. However, reports of aneurysms that rupture and communicate with another adjacent artery have not been found in the literature. CASE REPORT A 52-year-old man who underwent a renal transplantation in the left iliac fossa 21 years ago was admitted for chronic left lower abdominal pain that began 1 year ago. He did not have a history of any invasive procedures or severe trauma after the renal transplantation. Duplex ultrasound showed an oval-shaped hypoechoic structure adjacent to the left external iliac artery (EIA), with a swirling motion of blood flow inside. Computed tomography angiography showed an aneurysm of the left EIA, with a size of 35×34×47 mm, closely adjacent to or even communicating with the transplant renal artery (TRA). There was calcification in the aneurysm wall, without surrounding hematoma. The aneurysm was considered to be a true aneurysm, not a pseudoaneurysm. Endovascular therapy was performed. Digital subtraction angiography confirmed the communication between the aneurysm and the TRA. After the EIA was reconstructed with a covered stent, no leakage was demonstrated; however, contrast still flowed into the aneurysm though the TRA. A second covered stent graft was implanted in the TRA. Subsequently, the aneurysm was successfully excluded. CONCLUSIONS The pathogenesis of this strange aneurysm communicating with another adjacent artery is not well established. Stenting of multiple arteries was needed to treat this aneurysm.

Identification of potential nucleomodulins of Mycoplasma bovis by direct biotinylation and proximity-based biotinylation approaches.

Mycoplasma bovis (M. bovis) is a significant bovine pathogen associated with various diseases, including bovine bronchopneumonia and mastitis resulting in substantial economic losses within the livestock industry. However, the development of effective control measures for M. bovis is hindered by a limited understanding of its virulence factors and pathogenesis. Nucleomodulins are newly identified secreted proteins of bacteria that internalize the host nuclei to regulate host cell gene expression and serve as critical virulence factors. Although recent reports have initiated exploration of mycoplasma nucleomodulins, the efficiency of conventional techniques for identification is very limited. Therefore, this study aimed to establish high-throughput methods to identify novel nucleomodulins of M. bovis. Using a direct biotinylation (DB) approach, a total of 289 proteins were identified including 66 high abundant proteins. In parallel, the use of proximity-based biotinylation (PBB), identified 28 proteins. Finally, seven nucleomodulins were verified to be nuclear by transfecting the bovine macrophage cell line BoMac with the plasmids encoding EGFP-fused proteins and observed with Opera Phenix, including the known nucleomodulin MbovP475 and six novel nucleomodulins. The novel nucleomodulins were four ribosomal proteins (MbovP599, MbovP678, MbovP710, and MbovP712), one transposase (MbovP790), and one conserved hypothetical protein (MbovP513). Among them, one unique nucleomodulin MbovP475 was identified with DB, two unique nucleomodulins (MbovP513 and MbovP710) with PBB, and four nucleomodulins by both. Overall, these findings established a foundation for further research on M. bovis nucleomodulin-host interactions for identification of new virulence factors.

Evaluation of reference genes and expression patterns of CONSTANS-LIKE genes in Tetrastigma hemsleyanum under different photoperiods.

CONSTANS-LIKE (COL ) genes are a key signalling molecule that regulates plant growth and development during the photoperiod. Our preliminary experiments showed that the photoperiod greatly influence the formation of Tetrastigma hemsleyanum root tubers. In this study, we examined the oscillation patterns and expression characteristics of COL genes in leaves of T. hemsleyanum under different photoperiod conditions. Six genes were selected as candidate reference genes for further analyses: (1) 18S ribosomal RNA (18S rRNA ); (2) α-tubulin (TUBA ); (3) 30S ribosomal RNA (30S rRNA ); (4) TATA binding protein (TBP ); (5) elongation factor 1α (EF-1α ); and (6) RNA polymerase II (RPII ). The geNorm, NormFinder, and BestKeeper software programs were used to evaluate expression stability. Two ThCOL genes were screened in the T. hemsleyanum transcriptome library, and their expression patterns under different photoperiod conditions were analysed using quantitative reverse transcription PCR. The genes EF-1α , TUBA , and 18S rRNA were used to analyse the expression profiles of CONSTANS genes (ThCOL4 and ThCOL5 ) under different photoperiods. The expression peaks of ThCOL4 and ThCOL5 appeared at different times, demonstrating that their oscillation patterns were influenced by the photoperiod. We speculate that these two ThCOL genes may be involved in different biological processes.

M2-type tumor-associated macrophages upregulated PD-L1 expression in cervical cancer via the PI3K/AKT pathway.

BACKGROUND AND PURPOSE: PD-1/PD-L1 inhibitors have become a promising therapy. However, the response rate is lower than 30% in patients with cervical cancer (CC), which is related to immunosuppressive components in tumor microenvironment (TME). Tumor-associated macrophages (TAMs), as one of the most important immune cells, are involved in the formation of tumor suppressive microenvironment. Therefore, it will provide a theoretical basis for curative effect improvement about the regulatory mechanism of TAMs on PD-L1 expression. METHODS: The clinical data and pathological tissues of CC patients were collected, and the expressions of PD-L1, CD68 and CD163 were detected by immunohistochemistry. Bioinformatics was used to analyze the macrophage subtypes involved in PD-L1 regulation. A co-culture model was established to observe the effects of TAMs on the morphology, migration and invasion function of CC cells, and the regulatory mechanism of TAMs on PD-L1. RESULTS: PD-L1 expression on tumor cells could predict the poor prognosis of patients. And there was a strong correlation between PD-L1 expression with CD163+TAMs infiltration. Similarly, PD-L1 expression was associated with M1/M2-type TAMs infiltration in bioinformatics analysis. The results of cell co-culture showed that M1/M2-type TAMs could upregulate PD-L1 expression, especially M2-type TAMs may elevate the PD-L1 expression via PI3K/AKT pathway. Meanwhile, M1/M2-type TAMs can affect the morphological changes, and enhance migration and invasion abilities of CC cells. CONCLUSIONS: PD-L1 expression in tumor cells can be used as a prognostic factor and is closely related to CD163+TAMs infiltration. In addition, M2-type TAMs can upregulate PD-L1 expression in CC cells through PI3K/AKT pathway, enhance the migration and invasion capabilities, and affect the tumor progression.

Electron stochastic acceleration in laboratory-produced kinetic turbulent plasmas.

The origin of energetic charged particles in universe remains an unresolved issue. Astronomical observations combined with simulations have provided insights into particle acceleration mechanisms, including magnetic reconnection acceleration, shock acceleration, and stochastic acceleration. Recent experiments have also confirmed that electrons can be accelerated through processes such as magnetic reconnection and collisionless shock formation. However, laboratory identifying stochastic acceleration as a feasible mechanism is still a challenge, particularly in the creation of collision-free turbulent plasmas. Here, we present experimental results demonstrating kinetic turbulence with a typical spectrum k-2.9 originating from Weibel instability. Energetic electrons exhibiting a power-law distribution are clearly observed. Simulations further reveal that thermal electrons undergo stochastic acceleration through collisions with multiple magnetic islands-like structures within the turbulent region. This study sheds light on a critical transition period during supernova explosion, where kinetic turbulences originating from Weibel instability emerge prior to collisionless shock formation. Our results suggest that electrons undergo stochastic acceleration during this transition phase.

NADPH mimics the antidepressant effects of exercise in a chronic unpredictable stress rat model.

Exercise is known to be an effective intervention for depression. NADPH has been demonstrated to have neuroprotective effects in our previous studies. This study aimed to investigate if NADPH has antidepressant effects and can mimic the effects of exercise in a chronic unpredictable stress (CUS) rat model. CUS rats underwent an 8-week swimming exercise (30 min/d, 5d/w) or were intraperitoneally administered 4 mg/kg or 8 mg/kg NADPH. The open field test (OFT), sucrose preference test (SPT), novelty-suppressed feeding test (NSFT), and forced swimming test (FST) were used to examine the antidepressant-like behaviors of the rats. Exercise, 4 mg/kg, and 8 mg/kg NADPH similarly reduced anxiety, as demonstrated by the number of fecal pellets. Meanwhile, exercise and 8 mg/kg NADPH significantly increased locomotion activity in the OFT. Exercise, 4 mg/kg, and 8 mg/kg NADPH effectively reversed CUS-induced anhedonia in rats in the SPT. Exercise, 4 mg/kg, and 8 mg/kg NADPH had no impact on appetite of depressed rats; however, 8 mg/kg NADPH increased the rats' exploratory activity in the NSFT. Exercise, 4 mg/kg, and 8 mg/kg NADPH significantly reduced the immobility time of CUS model rats, while exercise and 8 mg/kg NADPH postponed the early CUS-induced "immobility" in the FST. These results demonstrated that NADPH has similar antidepressant-like effects to exercise in CUS-induced depression model rats and is a potential exercise-mimicking antidepressant.

Enhancing practicality of deep learning for crop disease identification under field conditions: insights from model evaluation and crop-specific approaches.

BACKGROUND: Crop diseases can lead to significant yield losses and food shortages if not promptly identified and managed by farmers. With the advancements in convolutional neural networks (CNN) and the widespread availability of smartphones, automated and accurate identification of crop diseases has become feasible. However, although previous studies have achieved high accuracy (>95%) under laboratory conditions (Lab) using mixed data sets of multiple crops, these models often falter when deployed under field conditions (Field). In this study, we aimed to evaluate disease identification accuracy under Lab, Field, and Mixed (Lab and Field) conditions using an assembled data set encompassing 14 diseases of apple (Malus × domestica Borkh.), potato (Solanum tuberosum L.), and tomato (Solanum lycopersicum L.). In addition, we investigated the impact of model architectures, parameter sizes, and crop-specific models (CSMs) on accuracy, using DenseNets, ResNets, MobileNetV3, EfficientNet, and VGG Nets. RESULTS: Our results revealed a decrease in accuracy across all models from Lab (98.22%) to Mixed (91.76%) to Field (71.55%) conditions. Interestingly, disease classification accuracy showed minimal variation across model architectures and parameter sizes: Lab (97.61-98.76%), Mixed (90.76-92.31%), and Field (68.56-73.81%). Although CSMs were found to reduce inter-crop disease misclassifications, they also led to a slight increase in intra-crop misclassifications. CONCLUSION: Our findings underscore the importance of enriching data representation and volumes over employing new model architectures. Furthermore, the need for more field-specific images was highlighted. Ultimately, these insights contribute to the advancement of crop disease identification applications, facilitating their practical implementation in farmer's fields. © 2024 Society of Chemical Industry.

Asthmatic patients with vitamin D deficiency: Can vitamin D supplementation make a difference.

BACKGROUND: Asthma is a major public health concern due to its persistent inflammation of the airways. The intricate and widely variable epidemiology of asthma among nations and populations is a result of the interplay between genetic, environmental, and socioeconomic factors. OBJECTIVE: This study aims to investigate whether VitD supplementation can reduce the frequency of exacerbations (including the frequency of exacerbations requiring systemic corticosteroids and the frequency of exacerbations necessitating trips to the hospital or emergency room, or both) and improve pulmonary function (clinical indicators such as the FEV1% predicted value). METHODS: Computers were used to search Pubmed, Medline, ISI Web of Science, Embase, Cachrane Library, CNKI, CBM, VIP, and the Wanfang Database. Asthma/asthma, VitD/VitD, lung function/lung function, retrieval time is from database setup to October 8, 2021, to search all randomized controlled trials (RCTs) on the effect of VitD on human asthma and to retroactively incorporate references to literature were all included in the search criteria. After rigorous screening, quality evaluation, and data extraction of the included literature by two reviewers independently, heterogeneity tests and sensitivity analyses were performed. RESULTS: The findings show that a total of 12 relevant studies meeting the inclusion criteria were finally included, including 649 cases in the experimental group and 646 cases in the control group. VitD intervention reduced the number of asthma exacerbations, including the rate of exacerbations requiring systemic corticosteroid therapy and the rate of acute exacerbations requiring emergency department or hospital visits or both. CONCLUSIONS: In the outcome of lung function (FEV1% predicted value), it was shown that VitD supplementation improved lung function; in the outcome of serum 25-hydroxyVitD levels, it was shown that VitD supplementation increased serum 25-hydroxyVitD levels.

A comparison of ultrasound volume navigation, O-arm navigation, and X-ray guidance for screw placement in minimally invasive transforaminal lumbar interbody fusion: a randomized controlled trial.

OBJECTIVE: To compare the differences between Ultrasound Volume Navigation (UVN), O-arm Navigation, and conventional X-ray fluoroscopy-guided screw placement in Minimally Invasive Transforaminal Lumbar Interbody Fusion (MIS-TLIF) surgeries. METHODS: A total of 90 patients who underwent MIS-TLIF due to lumbar disc herniation from January 2022 to January 2023 were randomly assigned to the UVN group, O-arm group, and X-ray group. UVN, O-arm navigation, and X-ray guidance were used for screw placement in the respective groups, while the remaining surgical procedures followed routine MIS-TLIF protocols. Intraoperative data including average single screw placement time, total radiation dose, and average effective radiation dose per screw were recorded and calculated. On the 10th day after surgery, postoperative X-ray and CT examinations were conducted to assess screw placement accuracy and facet joint violation. RESULTS: There were no significant differences in general characteristics among the three groups, ensuring comparability. Firstly, the average single screw placement time in the O-arm group was significantly shorter than that in the UVN group and X-ray group (P<0.05). Secondly, in terms of total radiation dose during surgery, for single-level MIS-TLIF, the O-arm group had a significantly higher radiation dose compared to the UVN group and X-ray group (P<0.05). However, for multi-level MIS-TLIF, the X-ray group had a significantly higher radiation dose than the O-arm group and UVN group (P<0.05). In terms of average single screw radiation dose, the O-arm group and X-ray group were similar (P>0.05), while the UVN group was significantly lower than the other two groups (P<0.05). Furthermore, no significant differences were found in screw placement assessment grades among the three groups (P>0.05). However, in terms of facet joint violation rate, the UVN group (10.3%) and O-arm group (10.7%) showed no significant difference (P>0.05), while the X-ray group (26.7%) was significantly higher than both groups (P<0.05). Moreover, in the UVN group, there were significant correlations between average single screw placement time and placement grade with BMI index (r = 0.637, P<0.05; r = 0.504, P<0.05), while no similar significant correlations were found in the O-arm and X-ray groups. CONCLUSION: UVN-guided screw placement in MIS-TLIF surgeries demonstrates comparable efficiency, visualization, and accuracy to O-arm navigation, while significantly reducing radiation exposure compared to both O-arm navigation and X-ray guidance. However, UVN may be influenced by factors like obesity, limiting its application.

Metagenomic analysis reveals altered gut virome and diagnostic potential in pancreatic cancer.

Pancreatic cancer (PC) is a highly aggressive malignancy with a poor prognosis, making early diagnosis crucial for improving patient outcomes. While the gut microbiome, including bacteria and viruses, is believed to be essential in cancer pathogenicity, the potential contribution of the gut virome to PC remains largely unexplored. In this study, we conducted a comparative analysis of the gut viral compositional and functional profiles between PC patients and healthy controls, based on fecal metagenomes from two publicly available data sets comprising a total of 101 patients and 82 healthy controls. Our results revealed a decreasing trend in the gut virome diversity of PC patients with disease severity. We identified significant alterations in the overall viral structure of PC patients, with a meta-analysis revealing 219 viral operational taxonomic units (vOTUs) showing significant differences in relative abundance between patients and healthy controls. Among these, 65 vOTUs were enriched in PC patients, and 154 were reduced. Host prediction revealed that PC-enriched vOTUs preferentially infected bacterial members of Veillonellaceae, Enterobacteriaceae, Fusobacteriaceae, and Streptococcaceae, while PC-reduced vOTUs were more likely to infect Ruminococcaceae, Lachnospiraceae, Clostridiaceae, Oscillospiraceae, and Peptostreptococcaceae. Furthermore, we constructed random forest models based on the PC-associated vOTUs, achieving an optimal average area under the curve (AUC) of up to 0.879 for distinguishing patients from controls. Through additional 10 public cohorts, we demonstrated the reproducibility and high specificity of these viral signatures. Our study suggests that the gut virome may play a role in PC development and could serve as a promising target for PC diagnosis and therapeutic intervention. Future studies should further explore the underlying mechanisms of gut virus-bacteria interactions and validate the diagnostic models in larger and more diverse populations.

The activation of adenosine monophosphate-activated protein kinase inhibits the migration of tongue squamous cell carcinoma cells by targeting Claudin-1 via epithelial-mesenchymal transition.

BACKGROUND: The role of Claudin-1 in tongue squamous cell carcinoma (TSCC) metastasis needs further clarification, particularly its impact on cell migration. Herein, our study aims to investigate the role of Claudin-1 in TSCC cell migration and its underlying mechanisms. METHODS: 36 TSCC tissue samples underwent immunohistochemical staining for Claudin-1. Western blotting and immunofluorescence analyses were conducted to evaluate Claudin-1 expression and distribution in TSCC cells. Claudin-1 knockdown cell lines were established using short hairpin RNA transfection. Migration effects were assessed through wound healing assays. Furthermore, the expression of EMT-associated molecules was measured via western blotting. RESULTS: Claudin-1 expression decreased as TSCC malignancy increased. Adenosine monophosphate-activated protein kinase (AMPK) activation led to increased Claudin-1 expression and membrane translocation, inhibiting TSCC cell migration and epithelial-mesenchymal transition (EMT). Conversely, Claudin-1 knockdown reversed these inhibitory effects on migration and EMT caused by AMPK activation. CONCLUSIONS: Our results indicated that AMPK activation suppresses TSCC cell migration by targeting Claudin-1 and EMT pathways.

Dihydromyricetin regulates KEAP1-Nrf2 pathways to enhance the survival of ischemic flap.

In clinical flap practice, there are a lot of studies being done on how to promote the survival of distal random flap necrosis in the hypoxic and ischemic state. As a traditional Chinese medicine, dihydromyricetin (DHM) is crucial in preventing oxidative stress and apoptosis in a number of disorders. In this work, we examined the impact of DHM on the ability to survive of ischemia flaps and looked into its fundamental mechanism. Our results showed that DHM significantly increased the ischemic flaps' survival area, encouraged angiogenesis and blood flow, reduced oxidative stress and apoptosis, and stimulated KEAP1-Nrf2 (Kelch-like ECH-associated protein 1-nuclear factor erythroid 2-related factor) signaling pathways. Adeno-associated virus (AAV) upregulation of KEAP1 expression also negated the favorable effects of DHM on flap survival. By activating KEAP1-Nrf2 signaling pathways, DHM therapy promotes angiogenesis while reducing oxidative stress and apoptosis.

Pathways linking watershed development and riparian quality to stream water quality and fish communities: Insights from 233 subbasins of the Great Lakes region.

Anthropogenic stressors such as urban development, agricultural runoff, and riparian zone degradation impair stream water quality and biodiversity. However, the intricate pathways that connect these stressors at watershed and riparian scales to stream ecosystems-and their interplay with climate and hydrology-remain understudied. In this study, we used Partial Least Squares (PLS) path modeling to examine these pathways and their collective impacts on stream water quality and fish community structures across 233 watersheds in the Great Lakes region. Our study suggests that moderate levels of watershed development enhance overall fish richness, potentially due to increased water temperature and nutrient availability, but reduces both the percentages and richness of cold water and intolerant taxa. Riparian quality exerts indirect effects on water quality with climate and stream order serving as key mediators. Complementing our SEM analysis, we also used Multiple Linear Regression (MLR) models and identified a significant positive relationship between the proportion of clay and agricultural land with TN concentrations. However, TP concentrations are influenced by a more complex set of interactions involving developed areas, soil, and slope. These findings emphasize the necessity of adopting integrated management strategies to preserve the health and integrity of freshwater ecosystems in the Great Lakes region. These strategies should integrate watershed and riparian protection measures while also taking into account the effects of climate change and specific local conditions.

The influence of prolonged but low intensity blue light on the physiological properties of root tubers and the accumulation of flavonoids in Tetrastigma hemsleyanum Diels et Gilg.

Tetrastigma hemsleyanum Diel et Gilg is a perennial herbaceous plant native to subtropical China with multiple medicinal applications. Supplementing with low-density blue light (BL) for 45 days (3 h/day) can not only significantly increase the yields of root tubers but also significantly increase the flavonoid content and its antioxidant activity. The chlorophyll content in the leaves of T. hemsleyanum significantly decreased, but the photosynthetic efficiency significantly increased after reaching the light saturation point. The production rate of superoxide anion radical in the leaves reached the highest peak after 1.5 h in BL and decreased at 3 h. The H2O2 content in the leaves decreased significantly, while the H2O2 content in the root tubers increased significantly at 3 h in BL. The objective of this research was to determine how the scavenging system, including antioxidant enzymes, antioxidants, and flavonoids respond to the oxidative stress induced by BL in root tubers. After exposure to BL, significant differences in the activity of APX and SOD were observed in the leaves and tubers within 3 h. By analyzing the upregulated flavonoids metabolites and key genes in metabolic pathways through the combined analysis of the flavonoid metabolic group and transcriptome in the root tubers, the upregulated accumulation of flavanols was found to be the main reason for the improvement in the antioxidant properties of flavonoids.

MicroRNA­17­5p alleviates sepsis­related acute kidney injury in mice by modulating inflammation and apoptosis.

Septic acute kidney injury (AKI) is considered as a severe and frequent complication that occurs during sepsis. Mounting evidence has confirmed the pivotal pathogenetic roles of microRNA (miRNA or miR) in sepsis­induced AKI; however, the role of miRNAs and their underlying mechanisms in sepsis­induced AKI have not been entirely understood. The present study aimed to elucidate the functions of special miRNAs during sepsis­induced AKI and its underlying mechanism. First, a number of differently expressed miRNAs was identified based on the microarray dataset GSE172044. Subsequently, lipopolysaccharide (LPS) was used to induce AKI in mice, and the role of miR­17­5p on AKI was clarified. Finally, the related molecular mechanisms were further examined by western blotting and immunohistochemical analysis. MiR­17­5p was found to be continuously decreased and reached the bottom at h 24 after AKI in mice. Functionally, injection of agomiR­17­5p could observably improve renal injury and survival rate, as well as inhibit inflammatory cytokine production and renal cell apoptosis in mice after AKI. On the contrary, injection of antagomiR­17­5p aggravated LPS­induced renal injury, inflammation and apoptosis in mice after AKI. Moreover, transforming growth factor ß receptor 2 (TGFßR2) was identified as a direct target of miR­17­5p, and its downstream phosphorylated Smad3 was also suppressed by miR­17­5p upregulation. Taken together, these results demonstrated that miR­17­5p overexpression may exhibit a beneficial effect by attenuating LPS­induced inflammation and apoptosis via regulating the TGFßR2/TGF­ß/Smad3 signaling pathway, indicating that miR­17­5p could act as a potential target for sepsis treatment.

Pd-Catalyzed Hydroboration of Vinylarenes with B2pin2.

A palladium(II)-catalyzed Markovnikov hydroboration of aryl alkenes with readily available bis(pinacolato)diboron (B2pin2) is reported. The reaction proceeded with low catalyst loading (0.5 mol %) in the absence of N- or P-containing ligands, affording the products in up to 90% yield. Trifluoracetic acid serves as the hydrogen source, enabling the synthesis of benzylic boronic esters under mild ambient conditions.