Engineering M1 macrophages with targeting aptamers for enhanced adoptive immunotherapy by modifying the cell surface.

Macrophages play a critical role in the body's defense against cancer by phagocytosing tumor cells, presenting antigens, and activating adaptive T cells. However, macrophages are intrinsically incapable of delivering targeted cancer immunotherapies. Engineered adoptive cell therapy introduces new targeting and antitumor capabilities by modifying macrophages to enhance the innate immune response of cells and improve clinical efficacy. In this study, we developed engineered macrophage cholesterol-AS1411-M1 (CAM1) for cellular immunotherapy. To target macrophages, cholesterol-AS1411 aptamers were anchored to the surface of M1 macrophages to produce CAM1 without genetic modification or cell damage. CAM1 induced significantly higher apoptosis/mortality than unmodified M1 macrophages in murine breast cancer cells. Anchoring AS1411 on the surface of macrophages provided a novel approach to construct engineered macrophages for tumor immunotherapy.

Construction and Validation of a Risk Prediction Model for Mild Cognitive Impairment in Non-Dialysis Chronic Kidney Disease Patient.

INTRODUCTION: The aims of this study are to explore the factors affecting mild cognitive impairment in patients with chronic kidney disease (CKD) who are not undergoing dialysis and to construct and validate a nomogram risk prediction model. METHODS: Using a convenience sampling method, 383 non-dialysis CKD patients from two tertiary hospitals in Chengdu were selected between February 2023 and August 2023 to form the modeling group. The patients were divided into a mild cognitive impairment group (n = 192) and a non-mild cognitive impairment group (n = 191), and factors such as demographics, disease data, and sleep disorders were compared between the two groups. Univariate and multivariate binary logistic regression analyses were used to identify independent influencing factors, followed by collinearity testing, and construction of the regression model. The final risk prediction model was presented through a nomogram and an online calculator, with internal validation using Bootstrap sampling. For external validation, 137 non-dialysis CKD patients from another tertiary hospital in Chengdu were selected between October 2023 and December 2023. RESULTS: In the modeling group, 192 (50.1%) of the non-dialysis CKD patients developed mild cognitive impairment, and in the validation group, 56 (40.9%) patients developed mild cognitive impairment, totaling 248 (47.7%) of all sampled non-dialysis CKD patients. Age, educational level, Occupation status, Use of smartphone, sleep disorders, hemoglobin, and platelet count were independent factors influencing the occurrence of mild cognitive impairment in non-dialysis CKD patients (all p < 0.05). The model evaluation showed an area under the ROC curve of 0.928, 95% CI (0.902, 0.953) in the modeling group, and 0.897, 95% CI (0.844, 0.950) in the validation group. The model's Youden index was 0.707, with an optimal cutoff value of 0.494, sensitivity of 0.853, and specificity of 0.854, indicating good predictive performance; calibration curves, Hosmer-Lemeshow test, and clinical decision curves indicated good calibration and clinical benefit. Internal validation results showed a consistency index (C-index) of 0.928, 95% CI (0.902, 0.953). CONCLUSION: The risk prediction model developed in this study shows excellent performance, demonstrating significant predictive potential for early screening of mild cognitive impairment in non-dialysis CKD patients. The application of this model will provide a reference for healthcare professionals, helping them formulate more targeted intervention strategies to optimize patient treatment and management outcomes.

The role of cells and their derivatives in otorhinolaryngologic diseases treatment.

Otolaryngology is an important specialty in the field of surgery that deals with the diagnosis and treatment of the ear, nose, throat, trachea, as well as related anatomical structures. Various otolaryngological disorders are difficult to treat using established pharmacological and surgical approaches. The advent of molecular and cellular therapies led to further progress in this respect. This article reviews the therapeutic strategies of using stem cells, immune cells, and chondrocytes in otorhinolaryngology. As the most widely recognized cell derivatives, exosomes were also systematically reviewed for their therapeutic potential in head and neck cancer, otitis media, and allergic rhinitis. Finally, we summarize the limitations of stem cells, chondrocytes, and exosomes, as well as possible solutions, and provide an outlook on the future direction of cell- and derivative-based therapies in otorhinolaryngology, to offer a theoretical foundation for the clinical translation of this therapeutic modality.

Effect of force direction and impaction angulation during dilaceration impacted central incisor traction: a finite element analysis.

BACKGROUND: The effects of traction forces at different angles on impacted central incisors(ICI)with varying inverted angles (IA) may be different. The objective of this study was to analyze the biomechanical effects of different force directions (FD) on developmentally inverted ICI with multi-angle variations and to offer insights and guidance for the treatment of inverted ICI. METHODS: Three-dimensional finite element method was employed to simulate clinical scenarios of inverted ICI traction. As such, 0.2 N of force (direction: antero-superior angles of 90°, 100°, 110°, 120°, and 130° relative to the long axis of the inverted ICI crown) was applied to the inverted ICI with inverse angles (IA) of 40°, 30°, 20°, 10° and 0°. Inverted ICI apical displacement and Von Mises stress on periodontal ligament (PDL) and alveolar bone were compared. RESULTS: IA and FD showed minimal influence on the stress distribution in the PDL, as higher stresses were concentrated in the apical region. The higher stresses in the alveolar bone are focused on the cervical and apical regions of the tooth. In particular, IA exerts a more significant impact on stress distribution in the alveolar bone than FD. The influence of IA on the apical displacement of inverted ICI is larger than that of FD. CONCLUSIONS: To promote the health of the root and periodontal tissues, it is recommended to use an angle of 100°-110° relative to the long axis of the ICI crown when dealing with a large IA (> 20°) developmentally inverted ICI. Conversely, an angle of 110°-120° can be used.

Enzyme/ROS dual-sensitive nanoplatform with on-demand Celastrol release capacity for enhanced ulcerative colitis therapy by ROS scavenging, microbiota rebalancing, inflammation alleviating.

BACKGROUND: The oral administration of drugs for treating ulcerative colitis (UC) is hindered by several factors, including inadequate gastrointestinal stability, insufficient accumulation in colonic lesions, and uncontrolled drug release. METHODS: A multiple sensitive nano-delivery system comprising ß-cyclodextrin (CD) and 4-(hydroxymethyl)phenylboronic acid (PAPE) with enzyme/reactive oxygen species (ROS) sensitivity was developed to load celastrol (Cel) as a comprehensive treatment for UC. RESULTS: Owing to the positive charge in the site of inflamed colonic mucosa, the negatively charged nanomedicine (Cel/NPs) could efficiently accumulate. Expectedly, Cel/NPs showed excellent localization ability to colon in vitro and in vivo tests. The elevated concentration of ROS and intestinal enzymes in the colon microenvironment quickly break the CD, resulting in Cel release partially to rebalance microbiota and recover the intestinal barrier. The accompanying cellular internalization of residual Cel/NPs, along with the high concentration of cellular ROS to trigger Cel burst release, could decrease the expression of inflammatory cytokines, inhibit colonic cell apoptosis, promote the macrophage polarization, scavenge ROS, and regulate the TLR4/NF-κB signaling pathway, which certified that Cel/NPs possessed a notably anti-UC therapy outcome. CONCLUSIONS: We provide a promising strategy for addressing UC symptoms via an enzyme/ROS-sensitive oral platform capable of releasing drugs on demand.

Risk prediction models for diabetic nephropathy among type 2 diabetes patients in China: a systematic review and meta-analysis.

Objective: This study systematically reviews and meta-analyzes existing risk prediction models for diabetic kidney disease (DKD) among patients with type 2 diabetes, aiming to provide references for scholars in China to develop higher-quality risk prediction models. Methods: We searched databases including China National Knowledge Infrastructure (CNKI), Wanfang Data, VIP Chinese Science and Technology Journal Database, Chinese Biomedical Literature Database (CBM), PubMed, Web of Science, Embase, and the Cochrane Library for studies on the construction of DKD risk prediction models among type 2 diabetes patients, up until 28 December 2023. Two researchers independently screened the literature and extracted and evaluated information according to a data extraction form and bias risk assessment tool for prediction model studies. The area under the curve (AUC) values of the models were meta-analyzed using STATA 14.0 software. Results: A total of 32 studies were included, with 31 performing internal validation and 22 reporting calibration. The incidence rate of DKD among patients with type 2 diabetes ranged from 6.0% to 62.3%. The AUC ranged from 0.713 to 0.949, indicating the prediction models have fair to excellent prediction accuracy. The overall applicability of the included studies was good; however, there was a high overall risk of bias, mainly due to the retrospective nature of most studies, unreasonable sample sizes, and studies conducted in a single center. Meta-analysis of the models yielded a combined AUC of 0.810 (95% CI: 0.780-0.840), indicating good predictive performance. Conclusion: Research on DKD risk prediction models for patients with type 2 diabetes in China is still in its initial stages, with a high overall risk of bias and a lack of clinical application. Future efforts could focus on constructing high-performance, easy-to-use prediction models based on interpretable machine learning methods and applying them in clinical settings. Registration: This systematic review and meta-analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, a recognized guideline for such research. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42024498015.

A prefrontal-habenular circuitry regulates social fear behaviour.

The medial prefrontal cortex (mPFC) has been implicated in the pathophysiology of social impairments including social fear. However, the precise subcortical partners that mediate mPFC dysfunction on social fear behaviour have not been identified. Employing a social fear conditioning paradigm, we induced robust social fear in mice and found that the lateral habenula (LHb) neurons and LHb-projecting mPFC neurons are synchronously activated during social fear expression. Moreover, optogenetic inhibition of the mPFC-LHb projection significantly reduced social fear responses. Importantly, consistent with animal studies, we observed an elevated prefrontal-habenular functional connectivity in subclinical individuals with higher social anxiety characterized by heightened social fear. These results unravel a crucial role of the prefrontal-habenular circuitry in social fear regulation and suggest that this pathway could serve as a potential target for the treatment of social fear symptom often observed in many psychiatric disorders.

Xiaowugui decoction alleviates experimental rheumatoid arthritis by suppressing Rab5a-mediated TLR4 internalization in macrophages.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by exacerbated synovial inflammation and joint destruction. Recent studies suggest toll-like receptor 4 (TLR4) internalization facilitate inflammatory response of macrophage. The role of TLR4 internalization in the pathogenesis of RA is unknown. PURPOSE: To investigate the role and mechanism of TLR4 internalization in macrophage inflammatory response of RA and explore whether TLR4 internalization mediates the anti-arthritic effect of Xiaowugui (XWG) decoction, a patented herbal formula used in China. METHODS: The co-expression of TLR4 and the internalization marker, early endosome antigen 1 (EEA1), in the synovial samples of RA patients and joint tissue of collagen-induced arthritis (CIA) mice, were evaluated using immunofluorescence. The effect of Rab5a-mediated early internalization of TLR4 on the activation induced by lipopolysaccharide (LPS) in RAW264.7 cells was investigated using small interfering RNAs that act against Rab5a. CIA was induced in Rab5a-/- mice to evaluate the role of Rab5a in vivo. The disease progression and expression of Rab5a and TLR4 in the joint tissue were evaluated in CIA mice treated with XWG. Inflammatory factors production, TLR4 internalization, and activation of downstream signaling pathways were examined in RAW264.7 cells treated with XWG in vitro. RESULTS: The co-expression and co-localization of TLR4 and EEA1 were elevated in the synovial samples of RA patients and joint tissue of CIA mice. Pharmaceutical inhibition of TLR4 internalization reduced macrophages inflammatory responses induced by LPS. The co-expression and co-localization of Rab5a and TLR4 were significantly increased in macrophages treated with LPS. Silencing Rab5a reduced LPS-induced TLR4 internalization, inflammatory factors production, and phosphorylation of Jun N-terminal kinases (JNK) and p65. Genetic deletion of Rab5a inhibited TLR4 internalization and the development of arthritis in vivo. The co-expression of TLR4 and Rab5a was also elevated in the synovial samples of RA patients. XWG treatment of mice with CIA alleviated arthritis and reduced the co-expression of Rab5a and TLR4 in the joint tissue. XWG treatment of macrophage inhibited LPS-induced IL-6 and TNF-α production, co-expression of Rab5a and TLR4, and phosphorylation of JNK and p65. CONCLUSIONS: Our findings highlight the pathogenic role of TLR4 internalization in patients with RA and identify a novel Rab5a-dependent internalization pathway that promotes macrophage inflammatory response. XWG treatment demonstrated outstanding therapeutic effects in experimental arthritis, and targeting the Rab5a-mediated internalization of TLR4 may be the main underlying mechanism.

Comparison of the efficacy and safety of vertebroplasty with different pedicle approaches for osteoporotic vertebral.

OBJECTIVE: To compare the efficacy and safety of vertebroplasty through different pedicle approaches in the treatment of osteoporotic vertebral compression fracture osteoporotic vertebral compression fractures (OVCF) by network meta-analysis. METHODS: Pubmed, Embase, Cochrane Library, Web of Science. Database for literature retrieval, retrieval time from the establishment of the database to April 2023, the randomized controlled trials of unilateral vertebroplasty (UVP), bilateral vertebroplasty (BVP), unilateral kyphoplasty (UKP), bilateral kyphoplasty (BKP), curved vertebroplasty (CVP) and curved kyphoplasty (CKP) were screened, evaluated and the data were extracted and included in the analysis. STATA 15.0 and ReMan 5.3 were used for data analysis. This study was registered in the National Institute for Health Research (NIHR) with the registration number CRD42023405181. RESULTS: This study included 16 articles with a total of 1712 patients. The order of visual analogue scale (VAS) improvement from good to bad is CVP > BVP > UVP > CKP > BKP > UKP. The order of kyphotic angles improvement from good to bad is CKP > UKP > UKP > UVP > BVP > CVP. The order of bone cement injection from less to more is UVP > CVP > UKP > CKP > BVP > BKP. The order of bone cement leakage rate from less to more is CKP > CVP > UKP > BKP > UVP > BVP. The order of X-ray exposure time from less to more is CKP > CVP > UVP > BVP > UKP > BKP. The order of operation time from less to more is CVP > UVP > UKP > CKP > BVP > BKP. CONCLUSION: For patients with kyphotic angles, kyphoplasty has unique advantages in improving kyphotic angles. But generally speaking, curved approach can optimize the distribution of bone cement through unilateral approach to achieve the orthopedic effect of bilateral approach, which is a minimally invasive technique with better curative effect and higher safety in the treatment of OVCF.

An improved 3D-UNet-based brain hippocampus segmentation model based on MR images.

OBJECTIVE: Accurate delineation of the hippocampal region via magnetic resonance imaging (MRI) is crucial for the prevention and early diagnosis of neurosystemic diseases. Determining how to accurately and quickly delineate the hippocampus from MRI results has become a serious issue. In this study, a pixel-level semantic segmentation method using 3D-UNet is proposed to realize the automatic segmentation of the brain hippocampus from MRI results. METHODS: Two hundred three-dimensional T1-weighted (3D-T1) nongadolinium contrast-enhanced magnetic resonance (MR) images were acquired at Hangzhou Cancer Hospital from June 2020 to December 2022. These samples were divided into two groups, containing 175 and 25 samples. In the first group, 145 cases were used to train the hippocampus segmentation model, and the remaining 30 cases were used to fine-tune the hyperparameters of the model. Images for twenty-five patients in the second group were used as the test set to evaluate the performance of the model. The training set of images was processed via rotation, scaling, grey value augmentation and transformation with a smooth dense deformation field for both image data and ground truth labels. A filling technique was introduced into the segmentation network to establish the hippocampus segmentation model. In addition, the performance of models established with the original network, such as VNet, SegResNet, UNetR and 3D-UNet, was compared with that of models constructed by combining the filling technique with the original segmentation network. RESULTS: The results showed that the performance of the segmentation model improved after the filling technique was introduced. Specifically, when the filling technique was introduced into VNet, SegResNet, 3D-UNet and UNetR, the segmentation performance of the models trained with an input image size of 48 × 48 × 48 improved. Among them, the 3D-UNet-based model with the filling technique achieved the best performance, with a Dice score (Dice score) of 0.7989 ± 0.0398 and a mean intersection over union (mIoU) of 0.6669 ± 0.0540, which were greater than those of the original 3D-UNet-based model. In addition, the oversegmentation ratio (OSR), average surface distance (ASD) and Hausdorff distance (HD) were 0.0666 ± 0.0351, 0.5733 ± 0.1018 and 5.1235 ± 1.4397, respectively, which were better than those of the other models. In addition, when the size of the input image was set to 48 × 48 × 48, 64 × 64 × 64 and 96 × 96 × 96, the model performance gradually improved, and the Dice scores of the proposed model reached 0.7989 ± 0.0398, 0.8371 ± 0.0254 and 0.8674 ± 0.0257, respectively. In addition, the mIoUs reached 0.6669 ± 0.0540, 0.7207 ± 0.0370 and 0.7668 ± 0.0392, respectively. CONCLUSION: The proposed hippocampus segmentation model constructed by introducing the filling technique into a segmentation network performed better than models built solely on the original network and can improve the efficiency of diagnostic analysis.

Human CD56+CD39+ dNK cells support fetal survival through controlling trophoblastic cell fate: immune mechanisms of recurrent early pregnancy loss.

Decidual natural killer (dNK) cells are the most abundant immune cells at the maternal-fetal interface during early pregnancy in both mice and humans, and emerging single-cell transcriptomic studies have uncovered various human dNK subsets that are disrupted in patients experiencing recurrent early pregnancy loss (RPL) at early gestational stage, suggesting a connection between abnormal proportions or characteristics of dNK subsets and RPL pathogenesis. However, the functional mechanisms underlying this association remain unclear. Here, we established a mouse model by adoptively transferring human dNK cells into pregnant NOG (NOD/Shi-scid/IL-2Rγnull) mice, where human dNK cells predominantly homed into the uteri of recipients. Using this model, we observed a strong correlation between the properties of human dNK cells and pregnancy outcome. The transfer of dNK cells from RPL patients (dNK-RPL) remarkably worsened early pregnancy loss and impaired placental trophoblast cell differentiation in the recipients. These adverse effects were effectively reversed by transferring CD56+CD39+ dNK cells. Mechanistic studies revealed that CD56+CD39+ dNK subset facilitates early differentiation of mouse trophoblast stem cells (mTSCs) towards both invasive and syncytial pathways through secreting macrophage colony-stimulating factor (M-CSF). Administration of recombinant M-CSF to NOG mice transferred with dNK-RPL efficiently rescued the exacerbated pregnancy outcomes and fetal/placental development. Collectively, this study established a novel humanized mouse model featuring functional human dNK cells homing into the uteri of recipients and uncovered the pivotal role of M-CSF in fetal-supporting function of CD56+CD39+ dNK cells during early pregnancy, highlighting that M-CSF may be a previously unappreciated therapeutic target for intervening RPL.

Exploring Protein Bioconjugation: A Redox-Based Strategy for Tryptophan Targeting.

Amino acid bioconjugation technology has emerged as a pivotal tool for linking small-molecule fragments with proteins, antibodies, and even cells. The study in Nature by Chang and Toste introduces a redox-based strategy for tryptophan bioconjugation, employing N-sulfonyloxaziridines as oxidative cyclization reagents, demonstrating high efficiency comparable to traditional click reactions. Meanwhile, this tool provides feasible methods for investigating the mechanisms underlying functional tryptophan-related biochemical processes, paving the way for protein function exploration, activity-based proteomics for functional amino acid identification and characterization, and even the design of covalent inhibitors.

Advanced gene therapy system for the treatment of solid tumour: A review.

In contrast to conventional therapies that require repeated dosing, gene therapy can treat diseases by correcting defective genes after a single transfection and achieving cascade amplification, and has been widely studied in clinical settings. However, nucleic acid drugs are prone to catabolism and inactivation. A variety of nucleic acid drug vectors have been developed to protect the target gene against nuclease degradation and increase the transformation efficiency and safety of gene therapy. In addition, gene therapy is often combined with chemotherapy, phototherapy, magnetic therapy, ultrasound, and other therapeutic modalities to improve the therapeutic effect. This review systematically introduces ribonucleic acid (RNA) interference technology, antisense oligonucleotides, and clustered regularly interspaced short palindromic repeat/CRISPR-associated nuclease 9 (CRISPR/Cas9) genome editing. It also introduces the commonly used nucleic acid drug vectors, including viral vectors (adenovirus, retrovirus, etc.), organic vectors (lipids, polymers, etc.), and inorganic vectors (MOFs, carbon nanotubes, mesoporous silica, etc.). Then, we describe the combined gene therapy modalities and the pathways of action and report the recent applications in solid tumors of the combined gene therapy. Finally, the challenges of gene therapy in solid tumor treatment are introduced, and the prospect of application in this field is presented.

RAD51B-AS1 promotes the malignant biological behavior of ovarian cancer through upregulation of RAD51B. / RAD51B-AS1通过上调RAD51B促进卵巢癌的恶性生物学行为.

Long non-coding RNAs (lncRNAs) play an indispensable role in the occurrence and development of ovarian cancer (OC). However, the potential involvement of lncRNAs in the progression of OC is largely unknown. To investigate the detailed roles and mechanisms ofRAD51 homolog B-antisense 1 (RAD51B-AS1), a novel lncRNA in OC, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to verify the expression of RAD51B-AS1. Cellular proliferation, metastasis, and apoptosis were detected using the cell counting kit-8 (CCK-8), colony-formation, transwell, and flow cytometry assays. Mouse xenograft models were established for the detection of tumorigenesis. The results revealed that RAD51B-AS1 was significantly upregulated in a highly metastatic human OC cell line and OC tissues. RAD51B-AS1 significantly increased the proliferation and metastasis of OC cells and enhanced their resistance to anoikis. Biogenetics prediction analysis revealed that the only target gene of RAD51B-AS1 was RAD51B. Subsequent gene function experiments revealed that RAD51B exerts the same biological effects as RAD51B-AS1. Rescue experiments demonstrated that the malignant biological behaviors promoted by RAD51B-AS1 overexpression were partially or completely reversed by RAD51B silencing in vitro and in vivo. Thus, RAD51B-AS1 promotes the malignant biological behaviors of OC and activates the protein kinase B (Akt)/B cell lymphoma protein-2 (Bcl-2) signaling pathway, and these effects may be associated with the positive regulation of RAD51B expression. RAD51B-AS1 is expected to serve as a novel molecular biomarker for the diagnosis and prediction of poor prognosis in OC, and as a potential therapeutic target for disease management.

Lithology and elevated temperature impact phoD-harboring bacteria on soil available P enhancing in subtropical forests.

Plants are generally limited by soil phosphorus (P) deficiency in forest ecosystems. Soil available P is influenced by lithology, temperature, and soil microbes. However, the interactive effects of these factors on soil P availability in subtropical forests remain unclear. To assess their impacts, we measured soil inorganic and available P fractions and the diversity, composition, and co-occurrence network of phoD-harboring bacteria in two contrasting forest soils (lithosols in karst forests and ferralsols in non-karst forests) in the subtropical regions of southwestern China across six temperature gradients. The present results showed that the complexities in composition and network and the diversity indices of phoD-harboring bacteria were higher in the karst forest soils than those in the non-karst forest soils, with marked differences in composition. In both types of forest soils, the complexities of composition and networks and the diversity indices were higher in the high-temperature regions (mean annual temperature (MAT) > 16 °C) compared to the low-temperature regions (MAT <16 °C). Soil total inorganic and available P contents were lower in the karst forest soils compared to the non-karst forest soils. Soil total available P contents were lower in the high temperature regions than those in the low temperature regions in both forest soils, whereas soil total inorganic P contents were contrary. Variance partitioning analysis showed that soil inorganic and available P fractions were predominantly explained by lithology and its interaction with soil microbes and climate. The present findings demonstrate that soil P availability in subtropical forests of southwestern China is influenced by lithology and temperature, which regulate the diversity, composition, and network connectivity of phoD-harboring bacteria. Furthermore, this study highlights the significance of controlling the composition of phoD-harboring bacteria for mitigating plant P deficiency in karst ecosystems.

Clinical intervention effect of Xuefu Zhuyu decoction on chronic heart failure complicated with depression.

BACKGROUND: The diagnosis and treatment of depression in patients with chronic heart failure (CHF) is challenging, with no ideal treatment at present. AIM: To analyze the clinical intervention effect of Xuefu Zhuyu decoction (XFZYD) on CHF complicated with depression. METHODS: The study cohort comprised 116 patients with CHF complicated with depression who received treatment from July 2020 to July 2023, of which 55 received Western medicine (control group) and 61 received XFZYD (research group). Data on clinical effectiveness, traditional Chinese medicine (TCM) syndrome score, cardiac function, negative emotions, and serum inflammatory factors, were collected for comparative analyses. RESULTS: Compared with the control group, the research group had an evidently higher total effective rate. Furthermore, there were marked reductions in TCM symptom score, left ventricular end-diastolic diameter, left ventricular end-systolic diameter, Self-Rating Depression Scale, Hamilton Depression Scale, high-sensitivity C-reactive protein, monocyte chemoattractant protein-1, and matrix metalloproteinase-9 in the research group after treatment, and these were lower than the corresponding values in the control group. Left ventricular ejection fraction was increased and higher in the research group compared with the control group after treatment. CONCLUSION: Our findings conclusively proved that XFZYD was considerably superior to Western medicine for treating CHF complicated with depression because it significantly alleviated patients' symptoms, improved cardiac function, relieved negative emotions, and reduced the levels of serum inflammatory factors.

Cytochrome P450 CYP81A104 in Eleusine indica confers resistance to multiherbicide with different modes of action.

BACKGROUND: Developing herbicide-resistant (HR) crop cultivars is an efficient way to control weeds and minimize crop yield losses. However, widespread and long-term herbicide application has led to the evolution of resistant weeds. Here, we established a resistant (R) E. indica population, collected from imidazolinone-resistant rice cultivar fields. RESULTS: The R population evolved 4.5-fold resistance to imazamox. Acetolactate synthase (ALS) gene sequencing and ALS activity assays excluded the effect of target-site resistance in this population. P450 inhibitor malathion pretreatment significantly reversed resistance to imazamox. RNA sequencing showed that a P450 gene CYP81A104 was expressed higher in R versus susceptible (S) plants. Arabidopsis overexpressing CYP81A104 showed resistance to ALS inhibitors (imazamox, tribenuron-methyl, penoxsulam and flucarbazone-sodium), PSII inhibitor (bentazone), hydroxyphenyl pyruvate dioxygenase inhibitor (mesotrione) and auxin mimics (MCPA), which was generally consistent with the results presented in the R population. CONCLUSION: This study confirmed that the CYP81A104 gene endowed resistance to multiherbicides with different modes-of-action. Our findings provide an insight into the molecular characteristics of resistance and contribute to formulating an appropriate strategy for weed management in HR crops. © 2024 Society of Chemical Industry.

Deciphering the connection between microvascular damage and neurodegeneration in early diabetic retinopathy.

Diabetic retinopathy (DR), a common diabetes complication leading to vision loss, presents early clinical signs linked to retinal vasculature damage, affecting the neural retina at advanced stages. However, vascular changes and potential effects on neural cells before clinical diagnosis of DR are less well understood. To study the earliest stages of DR we performed histological phenotyping and quantitative analysis on postmortem retinas from 10 donors with diabetes and without signs of DR (such as microaneurysms and haemorrhages), plus 3 controls and 1 DR case, focusing on capillary loss in the deeper (DVP) and superficial vascular plexuses (SVP) and neural retina effects. The advanced DR case exhibited profound vascular and neural damage, whereas the ten randomly selected donors with diabetes appeared superficially normal. The SVP was indistinguishable from the controls. In contrast, over half of the retinas from donors with diabetes showed capillary dropout in the DVP and increased capillary diameter. However, we could not detect any localised neural cell loss in the vicinity of dropout capillaries. Instead, we observed a subtle pan-retinal loss of inner nuclear layer (INL) cells in all diabetes cases (p<0.05), independent of microvascular damage. In conclusion, our findings demonstrate a novel histological biomarker for early-stage diabetes-related damage in human postmortem retina, common in people with diabetes before clinical DR diagnosis. Furthermore, the mismatch between capillary dropout and neural loss questions the notion of microvascular loss directly causing neurodegeneration at the earliest stages of DR, so diabetes may affect the two readouts independently.