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Abstract Glucagon-like peptide 1 (GLP1), which is mainly processed and cleaved from proglucagon in enteroendocrine cells (EECs) of the intestinal tract, acts on the GLP1 receptor in pancreatic cells to stimulate insulin secretion and to inhibit glucagon secretion. However, GLP1 processing is not fully understood. Here, we show that reticulon 4B (Nogo-B), an endoplasmic reticulum (ER)-resident protein, interacts with the major proglucagon fragment of proglucagon to retain proglucagon on the ER, thereby inhibiting PCSK1-mediated cleavage of proglucagon in the Golgi. Intestinal Nogo-B knockout in male type 2 diabetes mellitus (T2DM) mice increases GLP1 and insulin levels and decreases glucagon levels, thereby alleviating pancreatic injury and insulin resistance. Finally, we identify aberrantly elevated Nogo-B expression and inhibited proglucagon cleavage in EECs from diabetic patients. Our study reveals the subcellular regulatory processes involving Nogo-B during GLP1 production and suggests intestinal Nogo-B as a potential therapeutic target for T2DM.

Objective Weight is an influential factor in knee osteoarthritis (KOA). However, the effect of abnormal body weight on chitosan's efficacy in treating KOA is unclear. This study aimed to explore the differences in the effectiveness of arthroscopic surgery combined with intra‐articular chitosan injection for KOA in patients with abnormal body weight. Methods Patients with stage II‐III KOA (Kellgren–Lawrence rating, K‐L) undergoing arthroscopic surgery were recruited for this clinical study from January 2020 to September 2021. Based on body mass index (BMI) and intra‐articular chitosan injection, patients with KOA undergoing arthroscopic surgery (138 patients) were divided into four groups: low‐weight‐non‐injection (Lw‐N, BMI 0.05). The proportion of patients undergoing subsequent knee arthroplasty during the 2‐year follow‐up period was significantly higher in the Ow‐CS group (20/35) than in the Lw‐CS group (12/39) (p 0.05). Conclusion Arthroscopic surgery combined with intra‐articular chitosan injection shows short‐term positive effects in treating KOA. Intra‐articular chitosan injection appears to have a greater short‐term pain relief effect in obese patients.

Abstract With the assumption of densely distributed vegetation in PolInSAR processing, the height parameters can be inversed by the conventional random volume over ground (RVoG) method. During the procedure of RVoG, the samples used to estimate the PolInSAR coherence are selected directly from the neighbouring areas. However, for sparsely distributed vegetation, the scattering statistics are different from those of densely distributed vegetation. Therefore, the inversion performance will be deteriorated if the samples are selected directly in the neighbouring areas. A new phase‐based method is proposed to select samples, whose positions represent the volume scattering pixels, for sparsely distributed vegetation height inversion. By analysing the scattering characteristics of sparsely distributed vegetation, the processing data vector is formulated based on the amplitude‐normalised interferograms. With the PolSAR classification, the generalised inner product (GIP) is iteratively used to select the non‐local samples based on the formulated phase data vectors, which are utilised for sparsely distributed vegetation height inversion. For the selected sample sets, the vegetation distribution can be approximately regarded as “dense distribution”, and then the vegetation height parameters can be inversed by RVoG method. Compared to the height inversion performance based on different sample selection methods, the effectiveness of the proposed method is validated by the PolSARPro simulated data and the real airborne L‐band PolInSAR data.

Objective The connection between alterations in the disc structure following percutaneous endoscopic lumbar discectomy (PELD) and symptoms in patients postsurgery has not been reported yet. The purpose of the present study was to discuss the potential correlation between the changes in the morphological characteristics of various reference surfaces of the intervertebral disc after percutaneous endoscopic lumbar discectomy (PELD) and clinical outcomes, to identify the morphological parameters that affect efficacy and provide an evidence‐based foundation for assessing postoperative efficacy. Methods From October 2019 to October 2021, after percutaneous endoscopic lumbar discectomy (PELD), 98 individuals were enrolled. MRI DICOM data of the lumbar spine were obtained before and after surgery, specifically around 3 months. The morphological parameters of the operated and adjacent segments of the discs were measured using T2‐weighted images from three reference planes. Outcomes were assessed using the Oswestry disability index (ODI), visual analogue pain scores for the back and leg (VAS‐back/VAS‐leg), Japanese Orthopaedic Association (JOA) scores, and recovery rates. Postoperative changes in disc parameters and outcomes were compared between patients with different severity and types of LDH based on the MSU staging. Patients completed the questionnaire during outpatient follow‐up appointments 3, 6, and 12 months after the surgery. The follow‐up period was 14.69 ± 4.21 months, ranging from 12 to 24 months. Results Parameters such as area and circumference of intervertebral discs in the cross‐section were not associated with the change in the efficacy index. Postoperatively, a negative correlation between the variation of the disc height, disc height index, and protrusion distance and the difference in VAS scores for low back pain at 3 and 6 months was observed among the two sagittal change parameters. Differences between changes in disc imaging parameters and postoperative efficacy were not statistically significant between various types of lumbar disc herniation. Conclusion For the patients after percutaneous endoscopic lumbar discectomy, the changes in parameters such as disc area and circumference in the cross‐sectional plane are not associated with efficacy, and the changes in disc height and herniation distance in the sagittal plane provide a morphologic basis for the assessment of short‐term postoperative efficacy. In addition, the changes in disc morphologic parameters and postoperative efficacy do not differ between various types of lumbar disc herniation.

ObjectivesThis study aimed to explore the performance of a model based on Chinese Thyroid Imaging Reporting and Data Systems (C-TIRADS), clinical characteristics, and shear wave elastography (SWE) for the prediction of Bethesda I thyroid nodules before fine needle aspiration (FNA).Materials and methodsA total of 267 thyroid nodules from 267 patients were enrolled. Ultrasound and SWE were performed for all nodules before FNA. The nodules were scored according to the 2020 C-TIRADS, and the ultrasound and SWE characteristics of Bethesda I and non-I thyroid nodules were compared. The independent predictors were determined by univariate analysis and multivariate logistic regression analysis. A predictive model was established based on independent predictors, and the sensitivity, specificity, and area under the curve (AUC) of the independent predictors were compared with that of the model.ResultsOur study found that the maximum diameter of nodules that ranged from 15 to 20 mm, the C-TIRADS category

PurposeThis review aimed to assess the impact of different exercise dosages on cognitive function in individuals with post-stroke cognitive impairment (PSCI).MethodsFour electronic databases—Embase, PubMed, Web of Science, and Cochrane Library—were systematically searched from inception to 01 January 2024, focusing on the impact of exercise therapy on cognitive function in individuals with PSCI. Only randomized controlled trials meeting the criteria were included. The exercise therapy dose and adherence were evaluated following the American College of Sports Medicine (ACSM) guidelines, categorized into a high compliance group with ACSM recommendations and a low or uncertain compliance group. A random-effects model compared the effect of ACSM compliance on cognitive function in individuals with PSCI, with the effect size represented by the standardized mean difference (SMD) and a 95% confidence interval (CI).ResultsIn total, 18 studies meeting the criteria were included, with data from 1,742 participants. The findings suggested a beneficial effect of exercise on cognitive function in individuals with PSCI [SMD = 0.42, 95% CI (0.20, 0.65)]. Ten studies were categorized as the “high adherence group” and eight in the “low or uncertain adherence group” based on the ACSM recommendations. The subgroup analysis revealed that the SMD of the high compliance group was 0.46 (95% CI: 0.10, 0.82) (p = 0.01), while the SMD of the low or uncertain compliance group was 0.38 (95% CI: 0.07, 0.70) (p = 0.02).ConclusionOur study indicates the beneficial impact of exercise for patients with PSCI over no exercise. Furthermore, high adherence to the exercise dose recommended by ACSM guidelines demonstrated a more substantial improvement in cognitive function than low or uncertain adherence in patients with PSCI.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/#myprospero, identifier CRD42023487915.

Although data on the blockchain cannot be tampered with, malicious access by insiders can also lead to data leakage. Access records of block are an important basis for tracing the source of data breaches; however, access records themselves may be tampered with. Therefore, it is important to study how to protect the block access records. So far, the protection of block access records has not received much attention. To make block access records a protected data resource as well, this paper proposes a storage mechanism of data access record on consortium chain based on master-slave blocks. In this mechanism, the master block is used to store data resources, and the slave block of the master block is used to store access records of the master block. This method ensures that the slave block has the security characteristics of the single chain block, making the access record traceable and immutable. The storage mechanism's viability is confirmed by real-world experimentation. The proposed mechanism outperforms the single chain in terms of data query performance, according to the testing results on public data sets.

Focal segmental glomerulosclerosis (FSGS) is a type of chronic glomerular nephropathy showing characteristic glomerular sclerosis, diagnosed by kidney biopsy. However, it is difficult and expensive to monitor disease progression with repeated renal biopsy in clinical practice, and thus here we explored the feasibility of urine biomarkers as non‐invasive diagnostic tools. We downloaded scRNA‐seq datasets of 20 urine cell samples and 3 kidney tissues and obtained two gene lists encoding extracellular proteins for bioinformatic analysis; in addition, we identified key EP‐Genes by immunohistochemical staining and performed bulk RNA sequencing with 12 urine samples. We report that urine cells and kidney cells were correlated. A total of 64 EP‐Genes were acquired by intersecting genes of distal tubular cluster with extracellular proteins. Function enrichment analysis showed that EP‐Genes might be involved in the immune response and extracellular components. Six key EP‐Genes were identified and correlated with renal function. IMC showed that key EP‐Genes were located mainly in tubules. Cross verification and examination of a urine RNAseq dataset showed that SPP1 had diagnostic potential for FSGS. The presence of urine SPP1 was primarily associated with macrophage infiltration in kidney, and the pathogenesis of FSGS may be related to innate immunity. Urinary cells seemed to be strongly similar to kidney cells. In summary, SPP1 levels reflect renal function and may have potential as a biomarker for non‐invasive diagnosis of FSGS.

Background: Aortic dissection (AD) is a critical emergency in cardiovascular disease. AD occurs only in specific sites of the aorta, and the variation of shear stress in different aortic segments is a possible cause not reported. This study investigated the key molecules involved in shear stress-induced AD through quantitative bioinformatic analysis of a public RNA sequencing database and clinical tissue sample validation. Methods: Gene expression data from the GSE153434, GSE147026, and GSE52093 datasets were downloaded from the Gene Expression Omnibus. Next, differently expressed genes (DEGs) in each dataset were identified and integrated to identify common AD DEGs. STRING, Cytoscape, and MCODE were used to identify hub genes and crucial clustering modules, and Connectivity Map (CMap) was used to identify positive and negative agents. The same procedure was performed for the GSE160611 dataset to obtain shear stress-induced human aortic endothelial cell (HAEC) DEGs. After the integration of these two DEGs sets to identify shear stress-associated hub DEGs in AD, Gene Ontology Enrichment Analysis was performed. The common chemokine receptors and ligands in AD were identified by analyzing AD's three RNA sequencing datasets. Their origin was verified by analyzing AD single-cell sequencing data and validated by immunoblotting and immunofluorescence. Results: We identified 100 down-regulated and 50 up-regulated AD common DEGs. Enrichment results showed that common DEGs were closely related to blood vessel morphogenesis, muscle structure development, muscle tissue development, and chemotaxis. Among those DEGs, MYC, CCL2, and SPP1 are the three molecules with the highest degree. A crucial cluster of 15 genes was identified using MCODE, which contained inflammation-related genes with elevated expression and muscle cell-related genes with decreased expression, and CCL2 is central to immune-related genes. CMap confirmed MEK inhibitors and ALK inhibitors as possible therapeutic agents for AD. Moreover, 366 shear stress-associated DEGs in HAEC were identified in the GSE160611 dataset. After taking the intersection, we identified five shear stress-associated hub DEGs in AD (ANGPTL4, SNAI2, CCL2, GADD45B, and PROM1), and the enrichment analysis indicated they were related to the endothelial cell apoptotic process. Chemokine CCL2 was the molecule with a high degree in both DEG sets. Besides CCL2, CXCL5 was the only chemokine ligand differentially expressed in the three datasets. Additionally, immunoblotting confirmed the increased expression of CCL2 and CXCL5 in clinical tissue samples. Further research at the single-cell level revealed that CCL2 has multiple origins, and CXCL5 is macrophage-derived. Conclusion: Through integrative analysis, we identified core common AD DEGs and possible therapeutic agents based on these DEGs. We elucidated that the chemokine CCL2 and CXCL5-mediated “Endothelial-Monocyte-Neutrophil” axis may contribute to the development of shear stress-induced AD. These findings provide possible therapeutic targets for the prevention and treatment of AD.

Open-pit mining of coal mines in arid and semi-arid areas destroys surface morphology, accelerates soil water loss, and the lack of water resources seriously affects the effect of vegetation restoration in open pit dump. Soil reconstruction technology and microbial remediation technology point out the direction to solve the water shortage dilemma of vegetation in open pit dump, but the relationship between plant root morphological characteristics and soil water use efficiency under soil reconfiguration and the important role of dark septum endophytic fungi (DSE) in soil reconfiguration are not well understood. The purpose of this study was to explore the root growth and water use of maize under soil layer reconstruction mode, as well as the mechanism of DSE. The study object was maize, and the soil layer reconstruction experiment was simulated in a greenhouse for 4 months. The experiment was arranged in three groups: blank control(N-CK), soil layer reconstruction without DSE inoculation(L-CK), soil layer reconstruction with DSE inoculation(L-DSE). The results showed that: ① Compared with blank control treatment, the total root length of maize root system under soil layer reconstruction treatment was reduced by 39.7%, the proportion of fine roots less than 0.3mm in the root system was increased by 8.86%, and the water use efficiency of deep (50−70 cm) soil was increased by 16.1%. ② Compared with the reconstructed soil layer without DSE inoculation, the proline content in leaves of maize inoculated with DSE increased by 69.8%, the number of root tips and specific root length in 30−50 cm soil layer increased by 106.6% and 38.5%, respectively. In addition, the water use efficiency in deep soil increased by 29.3% and 11.1%, respectively, compared with that of N-CK and L-CK. ③ Root tip number and fine root volume of the maize root system are the key root characteristics to achieve efficient use of soil water under the soil layer reconstruction model. The combined study showed that soil layer reconstruction was helpful to optimize the root structure of maize, increase the proportion of fine roots and the number of root tips, and improve the water use pattern of maize under water shortage environment, and DSE inoculation under the soil layer reconfiguration model could improve the use rate of deep soil water by increasing the content of proline in leaves and optimizing the structure of maize root system, so as to improve the long-term drought resistance of crops.

Abstract There is substantial evidence that albumin-bound paclitaxel (nab-paclitaxel) is effective and safe for the treatment of breast, lung and pancreatic cancers. However, it can still cause adverse effects by affecting cardiac enzymes, hepatic enzyme metabolism and blood routine related indicators, which affects the use of chemotherapy for a full course of treatment. However, there are no relevant clinical studies to systematically observe the effects and dynamics of albumin-bound paclitaxel on cardiac enzymes, liver enzyme metabolism, and routine blood-related indices. The purpose of our study was to determine the levels of serum creatinine (Cre), aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), creatine kinase (CK), creatine kinase isoenzyme (CK-MB), white blood cells (WBC) and hemoglobin (HGB) in cancer patients treated with albumin-conjugated paclitaxel. This study retrospectively analyzed 113 patients with cancer. Patients who had received two cycles of nab-paclitaxel 260 mg/m2 (administered intravenously on days 1, 8, and 15 of each 28-day cycle) were selected. Serum Cre, AST, ALT, LDH, CK, and CK-MB activities, WBC counts, and HGB levels were measured before and after treatment with two cycles. Fourteen cancer types were analyzed. The distribution of cancer types in patients was mainly concentrated in lung, ovarian, and breast cancer. Nab-paclitaxel treatment markedly decreased Cre, AST, LDH, and CK activities in the serum and WBC counts and HGB levels, respectively. Serum Cre and CK activities and HGB levels were remarkably downregulated at baseline compared to healthy controls. Patients receiving nab-paclitaxel treatment cause metabolic disorders in tumor patients by reducing the decrease of Cre, AST, LDH, CK, CK-MB, WBC and HGB indexes, thus inducing the occurrence of cardiovascular events, hepatotoxic events and fatigue and other symptoms. Therefore, for tumor patients, although receiving nab-paclitaxel improves the anti-tumor effect, it is still necessary to closely monitor the changes of related enzymatic and routine blood indicators, so as to detect and intervene at an early stage.

Abstract Homologous recombination deficiency (HRD) testing has been approved by FDA for selecting epithelial ovarian cancer (EOC) patients who may benefit from the first-line poly (ADP-ribose) polymerase inhibitor (PARPi) maintenance therapy. However, the effects of HRD on the clinical outcomes of first-line chemotherapy and first-line PARPi maintenance therapy have not been rigorously evaluated in Chinese EOC patients. Here, we developed an HRD assay and applied it to two large retrospectively collected Chinese EOC patient cohorts. In the first-line adjuvant chemotherapy cohort (FACT, N = 380), HRD status significantly improved PFS (median, 15.6 months vs. 9.4 months; HR, 0.688; 95% CI, 0.526–0.899; P = 0.003) and OS (median, 89.5 months vs. 60.9 months; HR, 0.636; 95% CI, 0.423–0.955; P = 0.008). In the first-line PARPi maintenance therapy cohort (FPMT, N = 83), HRD status significantly improved PFS (median, NA vs. 12 months; HR, 0.438; 95% CI, 0.201–0.957; P = 0.033) and OS (median, NA vs. NA months; HR, 0.12; 95% CI, 0.029–0.505; P = 0.001). Our results demonstrate that HRD status is a significant predictor for PFS and OS in both first-line chemotherapy and first-line PARPi maintenance therapy, providing strong real-world evidence for conducting genetic testing and improving clinical recommendations for Chinese EOC patients.

Abstract Background Immunotherapy has emerged as an efficient therapeutic approach for cancer management. However, stimulation of host immune system against cancer cells often fails to achieve promising clinical outcomes mainly owing to the immunosuppressive characteristics of the tumor microenvironment (TME). Combination therapeutics that can trigger sustained immunogenic cell death (ICD) have provided new opportunities for cancer treatment. Methods In this study, we designed and applied an ICD inducer regimen, including a genetically engineered oncolytic virus (miRNA-modified coxsackieviruses B3, miR-CVB3), a pore-forming lytic peptide (melittin, found in bee venom), and a synthetic toll-like receptor 9 ligand (CpG oligodeoxynucleotides), for breast cancer and melanoma treatment. We compared the anti-tumor efficacy of miR-CVB3 and CpG-melittin (CpGMel) alone and in combination (miR-CVB3 + CpGMel) and investigated possible mechanisms involved. Results We demonstrated that miR-CVB3 + CpGMel had no major impact on viral growth, while enhancing the cellular uptake of CpGMel in vitro. We further showed that combination therapy led to significant increases in tumor cell death and release of damage-associated molecular patterns compared with individual treatment. In vivo studies in 4T1 tumor-bearing Balb/c mice revealed that both primary and distant tumors were significantly suppressed, and the survival rate was significantly prolonged after administration of miR-CVB3 + CpGMel compared with single treatment. This anti-tumor effect was accompanied by increased ICD and immune cell infiltration into the TME. Safety analysis showed no significant pathological abnormalities in Balb/c mice. Furthermore, the developed therapeutic regimen also demonstrated a great anti-tumor activity in B16F10 melanoma tumor-bearing C57BL/6 J mice. Conclusions Overall, our findings indicate that although single treatment using miR-CVB3 or CpGMel can efficiently delay tumor growth, combining oncolytic virus-based therapy can generate even stronger anti-tumor immunity, leading to a greater reduction in tumor size.

Abstract Objectives The compound betamethasone is widely used to prevent scarring in dermatology. This study aims to explore the effects of compound betamethasone on vocal fold (VF) wound healing. Study design Prospective animal study in rabbits. Methods Eighteen rabbits underwent bilateral VF stripping and three rabbits served as controls. 0.1 mL of compound betamethasone (1 mL: betamethasone sodium phosphate 5 mg and betamethasone dipropionate 2 mg) was injected into the right VF of each rabbit, and 0.1 mL 0.9% saline was injected into the contralateral VF. Endoscopy was performed for morphologic observation. Six larynges were harvested for histological analysis at 3 days, 7 days, and 1 month. The VFs were stained with hematoxylin and eosin (H&E), Alcian blue, and Masson' trichrome staining. Results In morphological analysis, there was no visible difference between betamethasone‐treated and saline‐treated VFs at 3 and 7 days. After 1 month, more VF scars appeared on the saline‐treated VFs than the VFs treated with betamethasone. Inflammatory cell number showed significant difference between both VFs at 3 days (p = .037) and 7 days (p = .045). No significant different was found in epithelial thickness at 1 month between the betamethasone and saline groups. The collagen in the saline‐treated VFs was significantly denser than that of the betamethasone‐treated group (p = .037). There was also a significant increase in the level of hyaluronic acid (HA) in betamethasone‐injected VFs in comparison to the saline‐injected VFs (p = .006). Conclusions Based on this study, compound betamethasone can improve VF healing. Our findings suggest that VF injection with compound betamethasone helps to minimize scarring by increasing HA level and decreasing collagen density.

BackgroundSubjective cognitive decline (SCD) is considered a preclinical stage of Alzheimer’s disease. However, reliable prevalence estimates of SCD in the Chinese population are lacking, underscoring the importance of such metrics for policymakers to formulate appropriate healthcare strategies.ObjectiveTo systematically evaluate SCD prevalence among older Chinese adults.MethodsPubMed, Web of Science, The Cochrane Library, Embase, CNKI, Wanfang, VIP, CBM, and Airiti Library databases were searched for studies on SCD in older Chinese individuals published before May 2023. Two investigators independently screened the literature, extracted the information, and assessed the bias risk of the included studies. A meta-analysis was then conducted using Stata 16.0 software via a random-effects model to analyze SCD prevalence in older Chinese adults.ResultsA total of 17 studies were included (n = 31,782). The SCD prevalence in older Chinese adults was 46.4% (95% CI, 40.6–52.2%). Further, subgroup analyzes indicated that SCD prevalence was 50.8% in men and 58.9% among women. Additionally, SCD prevalence in individuals aged 60–69, 70–79, and ≥ 80 years was 38.0, 45.2, and 60.3%, respectively. Furthermore, SCD prevalence in older adults with BMI 24.0 was 59.3, 54.0, and 52.9%, respectively. Geographically, SCD prevalence among older Chinese individuals was 41.3% in North China and 50.0% in South China. In terms of residence, SCD prevalence was 47.1% in urban residents and 50.0% among rural residents. As for retired individuals, SCD prevalence was 44.2% in non-manual workers and 49.2% among manual workers. In the case of education, individuals with an education level of “elementary school and below” had an SCD prevalence rate of 62.8%; “middle school, “52.4%; “high school, “55.0%; and “college and above, “51.3%. Finally, SCD prevalence was lower among married individuals with surviving spouses than in single adults who were divorced, widowed, or unmarried.ConclusionOur systematic review and meta-analysis identified significant and widespread SCD prevalence in the older population in China. Therefore, our review findings highlight the urgent requirement for medical institutions and policymakers across all levels to prioritize and rapidly develop and implement comprehensive preventive and therapeutic strategies for SCD.Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023406950, identifier: CRD42023406950.

Summary: Atherosclerosis, a leading health concern, stems from the dynamic involvement of immune cells in vascular plaques. Despite its significance, the interplay between chromatin remodeling and transcriptional regulation in plaque macrophages is understudied. We discovered the reduced expression of Baf60a, a component of the switch/sucrose non-fermentable (SWI/SNF) chromatin remodeling complex, in macrophages from advanced plaques. Myeloid-specific Baf60a deletion compromised mitochondrial integrity and heightened adhesion, apoptosis, and plaque development. BAF60a preserves mitochondrial energy homeostasis under pro-atherogenic stimuli by retaining nuclear respiratory factor 1 (NRF1) accessibility at critical genes. Overexpression of BAF60a rescued mitochondrial dysfunction in an NRF1-dependent manner. This study illuminates the BAF60a-NRF1 axis as a mitochondrial function modulator in atherosclerosis, proposing the rejuvenation of perturbed chromatin remodeling machinery as a potential therapeutic target.

Abstract Aneuploid refers to the gene dosage imbalance due to copy number alterations. Aneuploidy is generally harmful to the growth, development and reproduction of organisms according to the numerous research. However, it has rarely been reported on whether aneuploid have a relevant pattern of genome expression between the parental and its offspring generations. In this study, mRNA sequencing analysis was performed on rice (Oryza sativa L.) primary trisomes 11 and 12, same primary trisomes and normal individuals in their filial generation. We systematically summarized the changes in gene expression patterns that occur on cis genes and on trans genes between parental and filial generations. In T11 and T12, the ratio of cis-gene expression showed intermediate type in parents and dosage compensation in filial generations, which maybe due to more genes being downregulated. The trans genes were also affected by aneuploidy and manifested as cis-related. The strains with normal chromosomes in filial generations, there are still aneuploid-sensitive genes differentially expressed in their genomes, indicating that the effect of aneuploidy is far-reaching and could not be easily eliminated. Meanwhile, among these differentially expressed genes, genes with low-expression level were more likely to be upregulated, while genes with medium- and high-expression level were easy to be downregulated. For the different types of rice aneuploid, upregulated genes were mainly associated with genomic imbalance while downregulated genes were mainly influenced by the specific added chromosome. In conclusion, our results provide new insights into the genetic characterization and evolution of biological aneuploidy genomes.

Abstract Background Cotton Verticillium wilt, causing by Verticillium dahliae, has seriously affected the yield and quality of cotton. The incidence of Verticillium wilt in cotton fields has been on the rise for many years, especially after straw has been returned to the fields. Intercropping can reduce the incidence of soil borne diseases and is often used to control crop diseases, but the relationship between the effects of intercropping on microbial communities and the occurrence of plant diseases is unclear. This research explored the relationship between soil microbial community structure and Cotton Verticillium wilt in interplanting of cotton-onion, cotton-garlic, cotton-wheat and cotton monocultures. Amplicon sequencing applied to the profile of bacterial and fungal communities. Results The results showed that the disease index of Cotton Verticillium wilt was significantly reduced after intercropping with cotton-garlic and cotton-onion. Chao1 and Sobs indices were not significantly different in the rhizosphere soil and pre-plant soils of the four planting patterns, but the pre-plant fungal shannon index was significantly lower in the cotton-onion intercropping plot than in the other three plots. PCoA analysis showed that the soil microbial communities changed to a certain extent after intercropping, with large differences in the microbial communities under different cropping patterns. The abundance of Chaetomium was highest in the cotton-garlic intercropping before planting; the abundance of Penicillium was significantly higher in the cotton-wheat intercropping than in the other three systems. Conclusion Cotton-garlic and cotton-onion interplanting can control Cotton Verticillium wilt by affecting the soil microbial community. Fungi of the genera Chaetomium and Penicillium may be associated with plant disease resistance.

Coronarin (COR), an analog of jasmonic acid, has been shown to enhance the tolerance of plants to drought. However, the effects of COR on the interactions among microorganisms associated with plant roots and their implications for enhancing the drought tolerance of plants remain unclear. Here, we studied the effects of applying COR on the microorganisms associated with plant roots and the rhizosphere metabolome. Treatment with COR affected the fungal community of the rhizosphere by inducing changes in the rhizosphere metabolome, which enhanced the drought tolerance of plants. However, treatment with COR had no significant effect on root microorganisms or rhizosphere bacteria. Specifically, the application of COR resulted in a significant reduction in the relative abundance of metabolites, such as mucic acid, 1,4-cyclohexanedione, 4-acetylbutyric acid, Ribonic acid, palmitic acid, and stearic acid, in maize roots under drought conditions; COR application also led to increases in the abundance of drought-resistant fungal microorganisms, including Rhizopus, and the assembly of a highly drought-resistant rhizosphere fungal network, which enhanced the drought tolerance of plants. Overall, the results of our study indicate that COR application positively regulates interactions between plants and microbes and increases the drought tolerance of plants.

Abstract Background Tendinopathy is the leading sports-related injury and will cause severe weakness and tenderness. Effective therapy for tendinopathy remains limited, and extracellular vesicles (EVs) derived from adipose tissue-derived mesenchymal stem cells (ADMSCs) have demonstrated great potential in tendinopathy treatment; however, the influence of aging status on EV treatment has not been previously described. Results In this study, it was found that ADMSCs derived from old mice (ADMSCold) demonstrated remarkable cellular senescence and impaired NAD+ metabolism compared with ADMSCs derived from young mice (ADMSCyoung). Lower NAMPT contents were detected in both ADMSCold and its secreted EVs (ADMSCold-EVs). Advanced animal experiments demonstrated that ADMSCyoung-EVs, but not ADMSCold-EVs, alleviated the pathological structural, functional and biomechanical properties in tendinopathy mice. Mechanistic analyses demonstrated that ADMSCyoung-EVs improved cell viability and relieved cellular senescence of tenocytes through the NAMPT/SIRT1/PPARγ/PGC-1α pathway. ADMSCyoung-EVs, but not ADMSCold-EVs, promoted phagocytosis and M2 polarization in macrophages through the NAMPT/SIRT1/Nf-κb p65/NLRP3 pathway. The macrophage/tenocyte crosstalk in tendinopathy was influenced by ADMSCyoung-EV treatment and thus it demonstrated "One-Stone-Two-Birds" effects in tendinopathy treatment. Conclusions This study demonstrates an effective novel therapy for tendinopathy and uncovers the influence of donor age on curative effects by clarifying the detailed biological mechanism. Graphical Abstract

Understanding the molecular mechanisms that regulate flower growth, development, and opening is of paramount importance, yet these processes remain less explored at the genetic level. Flower development in Hydrangea paniculata ‘Vanilla Strawberry’ is finely tuned through hormonal signals, yet the genetic underpinnings are not well defined. This study addresses the gap by examining the influence of gibberellic acid (GA3), salicylic acid (SA), and ethylene (ETH) on the flowering traits and underlying molecular responses. Treatment with 100 mg/L SA significantly improved chlorophyll content and bolstered the accumulation of soluble sugars and proteins, advancing the flowering onset by 6 days and lengthening the flowering period by 11 days. Concurrently, this treatment enhanced inflorescence dimensions, increasing length, width, and petal area by 22.76%, 26.74%, and 27.45%, respectively. Contrastingly, 100 mg/L GA3 expanded inflorescence size but postponed flowering initiation and decreased inflorescence count. Higher concentrations of SA and GA3, as well as any concentration of ETH, resulted in delayed flowering and inferior inflorescence attributes. A physiological analysis over 50 days revealed that these regulators variably affected sugar and protein levels and modified antioxidant enzyme activities. An RNA-seq analysis during floral development highlighted significant transcriptomic reprogramming, with SA treatment downregulating Myb transcription factors, implicating them in the modulation of flowering timing and stress adaptation. These findings illuminate the complex interplay between hormonal treatments, gene expression, and flowering phenotypes in Hydrangea paniculata, offering valuable perspectives for ornamental horticulture optimization.

In recent years, the excessive of antibiotics in livestock and poultry husbandry, stemming from extensive industry experience, has resulted in the accumulation of residual antibiotics and antibiotic resistance genes (ARGs) in livestock manure. Composting, as a crucial approach for the utilization of manure resources, has the potential to reduce the levels of antibiotics and ARGs in manure, although complete elimination is challenging. Previous studies have primarily focused on the diversity and abundance of ARGs in compost or have solely examined the correlation between ARGs and their carriers, potentially leading to a misjudgment of the actual risk associated with ARGs in compost. To address this gap, this study investigated the transfer potential of ARGs in compost and their co-occurrence with opportunistic pathogenic bacteria by extensively analyzing metagenomic sequencing data of compost worldwide. The results demonstrated that the potential risk of ARGs in compost was significantly lower than in manure, suggesting that composting effectively reduces the risk of ARGs. Further analysis showed that the microbes shifted their life history strategy in manure and compost due to antibiotic pressure and formed metabolic interactions dominated by antibiotic-resistant microbes, increasing ARG dissemination frequency. Therefore, husbandry practice without antibiotic addition was recommended to control ARG evolution, dissemination, and abatement both at the source and throughout processing.

Specific and efficient smooth muscle cell–targeted (SMC-targeted) gene deletion is typically achieved by pairing SMMHC-CreERT2-Tg mice with mice carrying the loxP-flanked gene. However, the transgene, CreERT2, is not controlled by the endogenous Myh11 gene promoter, and the codon-modified iCreERT2 exhibits significant tamoxifen-independent leakage. Furthermore, because the Cre-bearing bacterial artificial chromosome (BAC) is inserted onto the Y chromosome, the SMMHC-CreERT2-Tg mice strain can only exhibit gene deletions in male mice. Additionally, there is a lack of Myh11-driven constitutive Cre mice when tamoxifen usage is a concern. We used CRISPR/Cas9-mediated homologous recombination between a donor vector carrying the CreNLSP2A or CreERT2–P2A sequence and homologous arm surrounding the translation start site of the Myh11 gene to generate Cre-knockin mice. The P2A sequence enables the simultaneous translation of Cre and endogenous proteins. Using reporter mice, we assessed Cre-mediated recombination efficiency, specificity, tamoxifen-dependent controllability, and functionality in both sexes. Both constitutive (Myh11-CreNLSP2A) and inducible (Myh11-CreERT2–P2A) Cre mice demonstrated efficient, SMC-specific, sex-independent Cre recombinase activity without confounding endogenous gene expression. Combined with recently generated BAC transgenic Myh11-CreERT2-RAD mice and the Itga8-CreERT2 mouse models, our models will help expand the research toolbox, facilitating unbiased and comprehensive research in SMCs and SMC-dependent cardiovascular diseases.

Objectives: Acute type A aortic dissection (ATAAD) with severe stenosis or occlusion of the true lumen of aortic arch branch vessels often leads to an increased incidence of severe postsurgical neurological complications and mortality rate. In this study, we aimed to introduce our institutional extra-anatomic revascularization and cannulation strategy with improved postoperative outcomes for better management of patients with cerebral malperfusion in the setting of ATAAD. Methods: Twenty-eight patients with ATAAD complicated by severe stenosis or occlusion of the aortic arch branch vessels, as noted on combined computed tomography angiography of the aorta and craniocervical artery, between January 2021 and June 2022 were included in this study. Basic patient characteristics, surgical procedures, hospitalization stays, and early follow-up results were analyzed. Results: The median follow-up duration was 16.5 months (interquartile range: 11.5–20.5), with a 100% completion rate. The 30-day mortality rates was 7.1% (2/28 patients); two patients had multiple cerebral infarctions on preoperative computed tomography and persistent coma. Postoperative transient neurological dysfunction occurred in 10.7% (3/28) of the patients, and no new permanent neurological dysfunction occurred. Of all the patients, 3.6% (1/28) had novel acute renal failure. No other deaths, secondary surgeries, or serious complications occurred during the early follow-up period. Conclusions: Use of extra-anatomic revascularization and a new cannulation strategy before cardiopulmonary bypass is safe and feasible and may reduce the high incidence of postoperative neurological complications in patients with ATAAD and cerebral malperfusion.

Abstract Background Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.

Abstract Background Approximately 80% of patients with blunt thoracic aortic injury (BTAI) die before reaching the hospital. Most people who survive the initial injury eventually die without appropriate treatment. This study analyzed and reported the treatment strategy of a single center for BTAI in the last 10 years and the early and middle clinical results. Methods This retrospective study included patients diagnosed with BTAI at Xijing Hospital from 2013 to 2022. All inpatients with BTAI aged ≥ 18 years were included in this study. The clinical data, imaging findings, and follow-up results were retrospectively collected and analyzed. The Kaplan–Meier curve and multivariate logistic regression were used to compare survivors and nonsurvivors. Results A total of 72 patients (57% men) were diagnosed with BTAI, with a mean age of 54.2 ± 9.1 years. The injury severity score was 24.3 ± 18, with Grade I BTAI1 (1.4%), Grade II 17 (23.6%), Grade III 52 (72.2%), and Grade IV 2 (2.8%) aortic injuries. Traffic accidents were the main cause of BTAI in 32 patients (44.4%). Most patients had trauma, 37 had rib fractures (51.4%), Sixty patients (83.3%) underwent thoracic endovascular aortic repair (TEVAR) surgery, eight (11.1%) underwent conservative treatment, and only four (5.6%) underwent open surgery. The overall hospitalization mortality was 12.5%. In multivariate logistic regression, elevated creatinine levels (P = 0.041) and high Glasgow coma scale (GCS) score (P = 0.004) were the predictors of hospital mortality. The median follow-up period was 57 (28–87) months. During the follow-up period, all-cause mortality was 5.6% and no aortic-related deaths were reported. Three patients (4.2%) needed secondary surgery and two of them underwent endovascular repair. Conclusion Although TEVAR surgery may be associated with intra- or postoperative dissection rupture or serious complications in the treatment of Grade III BTAI, the incidence rate was only 8.9%. Nevertheless, TEVAR surgery remains a safe and feasible approach for the treatment of Grade II or III BTAI, and surgical treatment should be considered first,. A high GCS score and elevated creatinine levels in the emergency department were closely associated with hospital mortality. Younger patients need long-term follow-up after TEVAR.

Accurate protein mapping on whole-tissue levels provides critical insights into diseases/therapies. Here, the authors described a novel spatial proteomics method, based on tissue compartmentalization using a 3D-printed micro-scaffold, generated thousands of protein maps across a whole-tissue slice.

Genetic modification of coxsackievirus B3 (CVB3) by inserting target sequences (TS) of tumor-suppressive and/or organ-selective microRNAs (miRs) into viral genome can efficiently eliminate viral pathogenesis without significant impacts on its oncolytic activity. Nonetheless, reversion mutants (loss of miR-TS inserts) were identified as early as day 35 post-injection in ∼40% immunodeficient mice. To improve the stability, here we re-engineered CVB3 by (1) replacing the same length of viral genome at the non-coding region with TS of cardiac-selective miR-1/miR-133 and pancreas-enriched miR-216/miR-375 or (2) inserting the above miR-TS into the coding region (i.e., P1 region) of viral genome. Serial passaging of these newly established miR-CVB3s in cultured cells for 20 rounds demonstrated significantly improved stability compared with the first-generation miR-CVB3 with 5′UTR insertion of miR-TS. The safety and stability of these new miR-CVB3s was verified in immunocompetent mice. Moreover, we showed that these new viruses retained the ability to suppress lung tumor growth in a xenograft mouse model. Finally, we observed that miR-CVB3 with insertion in P1 region was more stable than miR-CVB3 with preserved length of the 5′UTR, whereas the latter displayed significantly higher oncolytic activity. Overall, we presented here valid strategies to enhance the genomic stability of miR-CVB3 for virotherapy.

ABSTRACT Seed-associated microbiomes can impact the later colonization of a plant rhizosphere microbiome. However, there remains little insight into the underlying mechanisms concerning how alterations in the composition of the seed microbiome may intervene in the assembly of a rhizosphere microbiome. In this study, the fungus Trichoderma guizhouense NJAU4742 was introduced to both maize and watermelon seed microbiomes by seed coating. Application was found to significantly promote seed germination and improve plant growth and rhizosphere soil quality. The activities of acid phosphatase, cellulase, peroxidase, sucrase, and α-glucosidase increased significantly in two crops. The introduction of Trichoderma guizhouense NJAU4742 also led to a decrease in the occurrence of disease. Coating with T. guizhouense NJAU4742 did not alter the alpha diversities of the bacterial and fungal communities but formed a key network module that contained both Trichoderma and Mortierella. This key network module comprised of these potentially beneficial microorganisms was positively linked with the belowground biomass and activities of rhizosphere soil enzymes but negatively correlated with disease incidence. Overall, this study provides insights into plant growth promotion and plant health maintenance via seed coating in order to influence the rhizosphere microbiome. IMPORTANCE Seed-associated microbiomes can impact the rhizosphere microbiome assembly and function display. However, there remains little insight into the underlying mechanisms concerning how alterations in the composition of the seed microbiome with the beneficial microbes may intervene in the assembly of a rhizosphere microbiome. Here, we introduced T. guizhouense NJAU4742 to the seed microbiome by seed coating. This introduction led to a decrease in the occurrence of disease and an increase in plant growth; furthermore, it formed a key network module that contained both Trichoderma and Mortierella. Our study provides insights into plant growth promotion and plant health maintenance via seed coating in order to influence the rhizosphere microbiome.

Background: To investigate the correlation between corneal biomechanical characteristics (in vitro and in vivo) and corneal densitometry in myopia.Methods: The Pentacam (Oculus, Wetzlar, Germany) corneal densitometry (CD) and Corvis ST (Oculus, Wetzlar, Germany) exams were conducted prior to surgery for myopic patients who were intended to undergo small-incision lenticule extraction (SMILE). CD values (grayscale units, GSUs), and in vivo biomechanical parameters were obtained. The stromal lenticule was subjected to a uniaxial tensile test to obtain the elastic modulus E in vitro. We exam the correlations among in vivo, in vitro biomechanical characteristics and CD values.Results: In this study, 37 myopic patients (63 eyes) were included. The mean age of participants was 25.14 ± 6.74 years (range:16–39 years). The mean CD values of the total cornea, anterior layer, intermediate layer, posterior layer, 0–2 mm region and 2–6 mm region were 15.03 ± 1.23 GSU, 20.35 ± 1.98 GSU, 11.76 ± 1.01 GSU, 10.95 ± 0.83 GSU, 15.57 ± 1.12 GSU and 11.94 ± 1.77 GSU, respectively. Elastic modulus E (in vitro biomechanical indicator) was negatively correlated with intermediate layer CD (r = −0.35, p = 0.01) and 2–6 mm region CD (r = −0.39, p = 0.00). A negative correlation was also found between 0-2 mm central region CD and in vivo biomechanical indicator SP-HC (r = −0.29, p = 0.02).Conclusion: In myopic patients, densitometry is negatively correlated with biomechanical properties both in vivo and in vitro. With an increase in CD, the cornea deformed more easily.

Abstract Background Although dozens of studies have investigated the relationship between the content of serum cystatin C (Cys-C) and diabetic nephropathy (DN), the results are still controversial. Hence, This study aims to explore the accuracy of serum Cys-C for diagnosing DN by meta-analysis. Methods The studies about serum Cys-C diagnosing DN were searched from six online databases from inception to September 22, 2020. The data were processed by Stata 15.0 statistic software. The corresponding diagnostic effect sizes, such as sensitivity and specificity, were obtained. We drew a summary receiver operating characteristic (SROC) curve. We assess the risk of literature bias was following the QUADAS-2 guidelines. Results Twenty-six published studies were identified. The results showed a pooled sensitivity of 0.86 (95% confidence interval (CI): 0.82–0.90), specificity of 0.89 (95%CI: 0.85–0.92), positive likelihood ratio of 7.59 (95%CI: 5.66–10.19), negative likelihood ratio of 0.16 (95%CI: 0.12–0.21), and diagnostic odds ratio of 48.03 (95%CI: 30.64–75.29). The area under the SROC curve was given a value of 0.94 (95%CI: 0.91–0.96). Conclusion Serum cystatin C has an excellent diagnostic value with good sensitivity and specificity for diabetic nephropathy.

Abstract Granulomatous lobular mastitis (GLM) is a rare and chronic benign inflammatory disease of the breast. Difficulties exist in the management of GLM for many front-line surgeons and medical specialists who care for patients with inflammatory disorders of the breast. This consensus is summarized to establish evidence-based recommendations for the management of GLM. Literature was reviewed using PubMed from January 1, 1971 to July 31, 2020. Sixty-six international experienced multidisciplinary experts from 11 countries or regions were invited to review the evidence. Levels of evidence were determined using the American College of Physicians grading system, and recommendations were discussed until consensus. Experts discussed and concluded 30 recommendations on historical definitions, etiology and predisposing factors, diagnosis criteria, treatment, clinical stages, relapse and recurrence of GLM. GLM was recommended as a widely accepted definition. In addition, this consensus introduced a new clinical stages and management algorithm for GLM to provide individual treatment strategies. In conclusion, diagnosis of GLM depends on a combination of history, clinical manifestations, imaging examinations, laboratory examinations and pathology. The approach to treatment of GLM should be applied according to the different clinical stage of GLM. This evidence-based consensus would be valuable to assist front-line surgeons and medical specialists in the optimal management of GLM.