Leaf litter from Cynanchum auriculatum Royle ex Wight leads to root rot outbreaks by Fusarium solani, hindering continuous cropping.

Cynanchum auriculatum Royle ex Wight (CA) is experiencing challenges with continuous cropping obstacle (CCO) due to soil-borne fungal pathogens. The leaf litter from CA is regularly incorporated into the soil after root harvesting, but the impact of this practice on pathogen outbreaks remains uncertain. In this study, a fungal strain D1, identified as Fusarium solani, was isolated and confirmed as a potential factor in CCO. Both leave extract (LE) and root extract (RE) were found to inhibit seed germination and the activities of plant defense-related enzymes. The combinations of extracts and D1 exacerbated these negative effects. Beyond promoting the proliferation of D1 in soil, the extracts also enhanced the hypha weight, spore number, and spore germination rate of D1. Compared to RE, LE exhibited a greater degree of promotion in the activities of pathogenesis-related enzymes in D1. Additionally, caffeic acid and ferulic acid were identified as potential active compounds. LE, particularly in combination with D1, induced a shift in the composition of fungal communities rather than bacterial communities. These findings indicate that the water extract of leaf litter stimulated the growth and proliferation of fungal strain D1, thereby augmenting its pathogenicity toward CA and ultimately contributing to the CCO process.

Melanoma differentiation-associated protein 5 prevents cardiac hypertrophy via apoptosis signal-regulating kinase 1-c-Jun N-terminal kinase/p38 signaling.

Pathological cardiac hypertrophy (CH) is driven by maladaptive changes in myocardial cells in response to pressure overload or other stimuli. CH has been identified as a significant risk factor for the development of various cardiovascular diseases, ultimately resulting in heart failure. Melanoma differentiation-associated protein 5 (MDA5), encoded by interferon-induced with helicase C domain 1 (IFIH1), is a cytoplasmic sensor that primarily functions as a detector of double-stranded ribonucleic acid (dsRNA) viruses in innate immune responses; however, its role in CH pathogenesis remains unclear. Thus, the aim of this study was to examine the relationship between MDA5 and CH using cellular and animal models generated by stimulating neonatal rat cardiomyocytes with phenylephrine and by performing transverse aortic constriction on mice, respectively. MDA5 expression was upregulated in all models. MDA5 deficiency exacerbated myocardial pachynsis, fibrosis, and inflammation in vivo, whereas its overexpression hindered CH development in vitro. In terms of the underlying molecular mechanism, MDA5 inhibited CH development by promoting apoptosis signal-regulating kinase 1 (ASK1) phosphorylation, thereby suppressing c-Jun N-terminal kinase/p38 signaling pathway activation. Rescue experiments using an ASK1 activation inhibitor confirmed that ASK1 phosphorylation was essential for MDA5-mediated cell death. Thus, MDA5 protects against CH and is a potential therapeutic target.

A chromosome-level genome assembly of the forestry pest Coronaproctus castanopsis.

As an important forestry pest, Coronaproctus castanopsis (Monophlebidae) has caused serious damage to the globally valuable Gutianshan ecosystem, China. In this study, we assembled the first chromosome-level genome of the female specimen of C. castanopsis by merging BGI reads, HiFi long reads and Hi-C data. The assembled genome size is 700.81 Mb, with a scaffold N50 size of 273.84 Mb and a contig N50 size of 12.37 Mb. Hi-C scaffolding assigned 98.32% (689.03 Mb) of C. Castanopsis genome to three chromosomes. The BUSCO analysis (n = 1,367) showed a completeness of 91.2%, comprising 89.2% of single-copy BUSCOs and 2.0% of multicopy BUSCOs. The mapping ratio of BGI, second-generation RNA, third-generation RNA and HiFi reads are 97.84%, 96.15%, 97.96%, and 99.33%, respectively. We also identified 64.97% (455.3 Mb) repetitive elements, 1,373 non-coding RNAs and 10,542 protein-coding genes. This study assembled a high-quality genome of C. castanopsis, which accumulated valuable molecular data for scale insects.

Enhanced myofilament calcium sensitivity aggravates abnormal calcium handling and diastolic dysfunction in patient-specific induced pluripotent stem cell-derived cardiomyocytes with MYH7 mutation.

Hypertrophic cardiomyopathy (HCM), the most common inherited heart disease, is frequently caused by mutations in the ß-cardiac myosin heavy chain gene (MYH7). Abnormal calcium handling and diastolic dysfunction are archetypical features of HCM caused by MYH7 gene mutations. However, the mechanism of how MYH7 mutations leads to these features remains unclear, which inhibits the development of effective therapies. Initially, cardiomyocytes were generated from induced pluripotent stem cells from an eight-year-old girl diagnosed with HCM carrying a MYH7(C.1063 G>A) heterozygous mutation(mutant-iPSC-CMs) and mutation-corrected isogenic iPSCs(control-iPSC-CMs) in the present study. Next, we compared phenotype of mutant-iPSC-CMs to that of control-iPSC-CMs, by assessing their morphology, hypertrophy-related genes expression, calcium handling, diastolic function and myofilament calcium sensitivity at days 15 and 40 respectively. Finally, to better understand increased myofilament Ca2+ sensitivity as a central mechanism of central pathogenicity in HCM, inhibition of calcium sensitivity with mavacamten can improveed cardiomyocyte hypertrophy. Mutant-iPSC-CMs exhibited enlarged areas, increased sarcomere disarray, enhanced expression of hypertrophy-related genes proteins, abnormal calcium handling, diastolic dysfunction and increased myofilament calcium sensitivity at day 40, but only significant increase in calcium sensitivity and mild diastolic dysfunction at day 15. Increased calcium sensitivity by levosimendan aggravates cardiomyocyte hypertrophy phenotypes such as expression of hypertrophy-related genes, abnormal calcium handling and diastolic dysfunction, while inhibition of calcium sensitivity significantly improves cardiomyocyte hypertrophy phenotypes in mutant-iPSC-CMs, suggesting increased myofilament calcium sensitivity is the primary mechanisms for MYH7 mutations pathogenesis. Our studies have uncovered a pathogenic mechanism of HCM caused by MYH7 gene mutations through which enhanced myofilament calcium sensitivity aggravates abnormal calcium handling and diastolic dysfunction. Correction of the myofilament calcium sensitivity was found to be an effective method for treating the development of HCM phenotype in vitro.

A taxonomic study of Psyllaephagus Ashmead (Hymenoptera, Encyrtidae) from China.

Fifteen species of Psyllaephagus from China are studied. Three species, P.clavus Zou & Zhang, sp. nov., P.obliquus Zou & Zhang, sp. nov., and P.tangae Zou & Zhang, sp. nov., are described as new to science. A diagnosis or a description/redescription, figures of the characters, as well as the known distribution and hosts of each species are provided. A dichotomous key is also given to facilitate the identification of species.

Medical image analysis using deep learning algorithms.

In the field of medical image analysis within deep learning (DL), the importance of employing advanced DL techniques cannot be overstated. DL has achieved impressive results in various areas, making it particularly noteworthy for medical image analysis in healthcare. The integration of DL with medical image analysis enables real-time analysis of vast and intricate datasets, yielding insights that significantly enhance healthcare outcomes and operational efficiency in the industry. This extensive review of existing literature conducts a thorough examination of the most recent deep learning (DL) approaches designed to address the difficulties faced in medical healthcare, particularly focusing on the use of deep learning algorithms in medical image analysis. Falling all the investigated papers into five different categories in terms of their techniques, we have assessed them according to some critical parameters. Through a systematic categorization of state-of-the-art DL techniques, such as Convolutional Neural Networks (CNNs), Recurrent Neural Networks (RNNs), Generative Adversarial Networks (GANs), Long Short-term Memory (LSTM) models, and hybrid models, this study explores their underlying principles, advantages, limitations, methodologies, simulation environments, and datasets. Based on our results, Python was the most frequent programming language used for implementing the proposed methods in the investigated papers. Notably, the majority of the scrutinized papers were published in 2021, underscoring the contemporaneous nature of the research. Moreover, this review accentuates the forefront advancements in DL techniques and their practical applications within the realm of medical image analysis, while simultaneously addressing the challenges that hinder the widespread implementation of DL in image analysis within the medical healthcare domains. These discerned insights serve as compelling impetuses for future studies aimed at the progressive advancement of image analysis in medical healthcare research. The evaluation metrics employed across the reviewed articles encompass a broad spectrum of features, encompassing accuracy, sensitivity, specificity, F-score, robustness, computational complexity, and generalizability.

Konjac glucomannan attenuate high-fat diet-fed obesity through enhancing ß-adrenergic-mediated thermogenesis in inguinal white adipose tissue in mice.

Konjac glucomannan (KGM) has been reported to prevent high-fat diet-induced obesity, and we study investigated whether dietary supplementation with KGM can prevent obesity by increasing energy expenditure in inguinal white adipose tissue (iWAT) of high-fat diet (HF) -fed mice. Weaned mice fed the control diet (Con), HF, or HF plus KGM (8%, w/w, HFK) were divided into three groups. The results showed that 10-week supplementation with KGM significantly reduced partial adipose tissue weight and body weight, and improved glucose tolerance. Compared to the HF group, plasma lipid concentrations in the HFK group were greatly decreased to the control level. Moreover, transcriptomic research has shown that genes that are mainly associated with energy and lipid metabolism are significantly altered in iWAT. Mechanistically, KGM stimulated thermogenesis by promoting the expression of uncoupling protein-1 (UCP1) and the ß3-adrenergic receptor (ADR3ß). Taken together, our results suggest that dietary supplementation with konjac glucomannan can effectively alleviate obesity induced by a high-fat diet by activating ADR3ß-mediated iWAT thermogenesis. Dietary supplementation with KGM can effectively alleviate high fat diet- induced obesity mice by via activating ADR3ß-mediated thermogenesis of iWAT.

RGS16 regulates Hippo-YAP activity to promote esophageal cancer cell proliferation and migration.

Esophageal Squamous Cell Carcinoma (ESCC) is a common malignant tumor of digestive tract, accounting for 90% of all pathological types of esophageal cancer. Despite the rapid development of multi-disciplinary treatment such as surgery, chemotherapy, radiotherapy and chemoradiotherapy, the prognosis of patients with ESCC is still poor. Regulators of G-protein signaling (RGSs) are involved in the processes of various cancers. The expression levels of its family member RGS16 are abnormally elevated in a variety of tumors, but its role in ESCC is still unclear. We found that RGS16 expression is aberrantly increased in ESCC tissues and correlated with poor prognosis of ESCC patients from The Cancer Genome Atlas (TCGA) database and our collected ESCC tissues. Moreover, knockdown of RGS16 in two ESCC cells could indeed inhibit their proliferation and migration. We further explored the molecular mechanism of RGS16 in ESCC, and the correlation analysis from TCGA database showed that the mRNA levels of RGS16 was positively correlated with that of CTGF and CYR61, two target genes of Hippo-YAP signaling. Consistently, RGS16- knockdown significantly inhibited the expression of CTGF and CYR61 in ESCC cells. We found that the phosphorylation levels of LATS1 and YAP were significantly increased and YAP translocated into the cytoplasm after depletion of RGS16 in ESCC cells. Also, RGS16-knockdown promoted the interaction between LATS1 and upstream kinase MST1. In addition, reintroduction of a constitutive active YAP5A mutant significantly rescued CTGF expression and cell proliferation in RGS16-knockdown cells. Together, our work revealed that RGS16 promoted YAP activity through disrupting the interaction between LATS1 and MST1, thus promoting the proliferation and migration of ESCC cells.

Clinical assessment of VSR site and size and its relation to the severity of heart failure in post-myocardial infarction ventricular septal rupture patients.

BACKGROUND: Ventricular septal rupture (VSR) is a rare but well-known mechanical consequence of an acute myocardial infarction (AMI). Even in the later stages of re-perfusion therapy, the result of VSR remains poor. Our aim is to assess the site and size of VSR in relation to the severity of cardiac failure. METHODS: From January 2016 to December 2022, a total of 71 patients with a diagnosis of post-myocardial infarction VSR were admitted to the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. Data records were retrospectively included in this registry. In all patients, clinical and echocardiographic data were gathered, and statistical analyses were performed. RESULTS: A total of 71 consecutive patients (mean age: 66.27 ± 8.88 years); 50.7% male, 49.3% female, with (M:F) ratio of almost (1:1). Left ventricular ejection fraction (LVEF) was (48.55 ± 10.44%) on echocardiography, and apical VSR was the most common site (69.0%). Overall, the VSD site was strongly related to the VSD size (p = .016), LVEF (p = .012), AMI site (p = .001), and affected coronary vessel (p = .004). Prodromal angina (p = .041), intra-aortic balloon pump (p = .002), affected coronary vessels (p = .020), pro-BNP (p = .000), and LVEF (p = .017) were predictors of the severity of heart failure. CONCLUSIONS: Diabetes mellitus is a common risk factor for post-myocardial infarction VSR. VSR site and size had no relation to the severity of heart failure. A presentation with prodromal angina predicted severe heart failure and a worse prognosis.

Endothelial cell-released extracellular vesicles trigger pyroptosis and vascular inflammation to induce atherosclerosis through the delivery of HIF1A-AS2.

Extracellular vesicles (EVs) possess great potential in the modulation of cardiovascular diseases. Our current work intended to assay the clinical significance of endothelial cell (EC)-derived EVs in atherosclerosis (AS). Expression of HIF1A-AS2, miR-455-5p, and ESRRG in plasma from AS patients and mice and EVs from ox-LDL-treated ECs was measured. Interactions among HIF1A-AS2, miR-455-5p, ESRRG, and NLRP3 were analyzed. Next, EVs were co-cultured with ECs, and ectopic expression and depletion experimentations of HIF1A-AS2, miR-455-5p, ESRRG, and/or NLRP3 were carried out to assay their roles in pyroptosis and inflammation of ECs in AS. At last, the effects of HIF1A-AS2 shuttled by EC-derived EVs on EC pyroptosis and vascular inflammation in AS were verified in vivo. HIF1A-AS2 and ESRRG were highly expressed, while miR-455-5p was poorly expressed in AS. HIF1A-AS2 could sponge miR-455-5p to elevate the expression of ESRRG and NLRP3. Both in vitro and in vivo experiments revealed that ECs-derived EVs carrying HIF1A-AS2 induced the pyroptosis and vascular inflammation of ECs to promote the progression of AS by sponging miR-455-5p via ESRRG/NLRP3. HIF1A-AS2 shuttled by ECs-derived EVs can accelerate the progression of AS by downregulating miR-455-5p and upregulating ESRRG and NLRP3.

Two new species of Coccophagus Westwood (Hymenoptera: Aphelinidae) from China.

The malthusi group of Coccophagus Westwood (Hymenoptera: Aphelinidae) is characterized by a densely setose mesoscutellum with the posterior apical pair of setae distinctly longer than others. In the present paper, two new species of the malthusi group are described from China: Coccophagus infuscatus sp. nov. and Coccophagus bandus sp. nov., both reared from species of Coccidae (Hemiptera: Sternorrhyncha). The type specimens are housed in Institute of Zoology, Chinese Academy of Sciences (IZCAS), Beijing, China.

TRIM-containing 44 aggravates cardiac hypertrophy via TLR4/NOX4-induced ferroptosis.

TRIM-containing 44 (TRIM44) is a promoter of multiple cancers. However, its role in cardiac hypertrophy has not been elucidated. This study explored the role of TRIM44 on pressure overload-induced cardiac hypertrophy in mice. Mice were subjected to aortic banding to establish an adverse cardiac hypertrophy model, followed by the administration of AAV9-TRIM44 or AAV9shTRIM44 to overexpress or knock down TRIM44. Echocardiography was used to assess cardiac function. H9c2 cells were cultured and transfected with either Ad-TRIM44 or TRIM44 siRNA to overexpress or silence TRIM44. Cells were also stimulated with angiotensin II to establish a cardiomyocyte hypertrophy model. Results indicated that TRIM44 was downregulated in mice hearts and cardiomyocytes that were treated with aortic banding or angiotensin II. TRIM44 overexpression in mice hearts aggravated cardiac hypertrophy and fibrosis, as well as inhibited cardiac function post-aortic banding. Moreover, mice with TRIM44 overexpression displayed increased ferroptosis post-aortic banding. Mice with TRIM44 knockdown revealed ameliorated cardiac hypertrophy, ferroptosis, and fibrosis, as well as improved cardiac function post-aortic banding. In H9c2 cells transfected with Ad-TRIM44, angiotensin II-induced ferroptosis was enhanced, while cells with silenced TRIM44 reported reduced ferroptosis post-angiotensin II administration. Furthermore, TRIM44 interacted with TLR4, which increased the expression of NOX4 and subsequently augmented ferroptosis-associated protein levels. By using TLR4 knockout mice, the inhibitory role of TRIM44 was reduced post-aortic banding. Taken together, TRIM44 aggravated pressure overload-induced cardiac hypertrophy via increased TLR4/NOX4-associated ferroptosis. KEY MESSAGES: TRIM44 could aggregate pressure overload-induced cardiac hypertrophy via increasing TLR4-NOX4 associated ferroptosis. Target TRIM44 may become a new therapeutic method for preventing or treating pressure overload-induced cardiac hypertrophy.

Retraction: LncRNA NEXN-AS1 attenuates proliferation and migration of vascular smooth muscle cells through sponging miR-33a/b.

[This retracts the article DOI: 10.1039/C9RA06282C.].

E3 ubiquitin ligase RNF5 attenuates pathological cardiac hypertrophy through STING.

Ring-finger protein 5 (RNF5) is an E3 ubiquitin ligase which is expressed in a variety of human tissues. RNF5 is involved in the regulation of endoplasmic reticulum stress, inflammation, and innate immunity and plays an important role in the occurrence and development of various tumors. However, the role of RNF5 in cardiac hypertrophy has not been reported. In this study, we found the expression of RNF5 was increased in the hearts of mice with pathological cardiac hypertrophy. The loss-of-function research demonstrated that RNF5 deficiency exacerbated cardiac hypertrophy, whereas gain-of-function studies revealed that overexpression of RNF5 had opposite effects. The stimulator of interferon genes (STING) is a signaling molecule that can activate type I interferon immunity, which can meditate inflammation and immune response in many diseases. The protein-protein interaction experiments confirmed that STING interacted with RNF5. Further studies showed that RNF5 inhibited cardiac hypertrophy by promoting STING degradation through K48-linked polyubiquitination. Therefore, we defined RNF5 as importantly regulated signaling for cardiac hypertrophy.

Myotubularin-Related Protein14 Prevents Neointima Formation and Vascular Smooth Muscle Cell Proliferation by Inhibiting Polo-Like Kinase1.

Background Restenosis is one of the main bottlenecks in restricting the further development of cardiovascular interventional therapy. New signaling molecules involved in the progress have continuously been discovered; however, the specific molecular mechanisms remain unclear. MTMR14 (myotubularin-related protein 14) is a novel phosphoinositide phosphatase that has a variety of biological functions and is involved in diverse biological processes. However, the role of MTMR14 in vascular biology remains unclear. Herein, we addressed the role of MTMR14 in neointima formation and vascular smooth muscle cell (VSMC) proliferation after vessel injury. Methods and Results Vessel injury models were established using SMC-specific conditional MTMR14-knockout and -transgenic mice. Neointima formation was assessed by histopathological methods, and VSMC proliferation and migration were assessed using fluorescence ubiquitination-based cell cycle indicator, transwell, and scratch wound assay. Neointima formation and the expression of MTMR14 was increased after injury. MTMR14 deficiency accelerated neointima formation and promoted VSMC proliferation after injury, whereas MTMR14 overexpression remarkably attenuated this process. Mechanistically, we demonstrated that MTMR14 suppressed the activation of PLK1 (polo-like kinase 1) by interacting with it, which further leads to the inhibition of the activation of MEK/ERK/AKT (mitogen-activated protein kinase kinase/extracellular-signal-regulated kinase/protein kinase B), thereby inhibiting the proliferation of VSMC from the medial to the intima and thus preventing neointima formation. Conclusions MTMR14 prevents neointima formation and VSMC proliferation by inhibiting PLK1. Our findings reveal that MTMR14 serves as an inhibitor of VSMC proliferation and establish a link between MTMR14 and PLK1 in regulating VSMC proliferation. MTMR14 may become a novel potential therapeutic target in the treatment of restenosis.

Dual-specificity phosphatase 12 attenuates oxidative stress injury and apoptosis in diabetic cardiomyopathy via the ASK1-JNK/p38 signaling pathway.

Diabetic cardiomyopathy (DCM) is ventricular dysfunction that occurs in patients with diabetes mellitus (DM), independent of recognized risk factors, such as coronary artery disease, hypertension, and valvular heart disease. Dual-specificity phosphatase 12 (DUSP12) is a dual-specificity phosphatase expressed in all tissues. Genome-wide linkage studies have found an association between DUSP12 and type 2 diabetes (T2D). However, the role of DUSP12 in DCM remains largely unknown. Ubiquitously expressed DUSP12 is involved in nonalcoholic fatty liver disease, bacterial infection, and myocardial hypertrophy and plays a critical role in tumorigenesis. Herein, we observed an increased expression of DUSP12 in a hyperglycemia cell model and a high-fat diet (HFD) mouse model. Heart-specific DUSP12-deficient mice showed severe cardiac dysfunction and remodeling induced by an HFD. DUSP12 deficiency exacerbated oxidative stress injury and apoptosis, whereas DUSP12 overexpression had the opposite effect. At the molecular level, DUSP12 physically bound to apoptotic signal-regulated kinase 1 (ASK1), promoted its dephosphorylation, and inhibited its action on c-Jun N-terminal kinase and p38 mitogen-activated protein kinase. Rescue experiments have shown that oxidative stress injury and apoptosis, exacerbated by DUSP12 deficiency, are alleviated by ASK1 inhibition. Therefore, we consider DUSP12 an important signaling pathway in DCM.

Different Doses of Empagliflozin in Patients with Heart Failure with Reduced Ejection Fraction.

It was unclear whether there are discrepancies among the efficacy and safety of different doses of empagliflozin in patients with heart failure with reduced ejection fraction (HFrEF). The aim of this study was to compare the efficacy and safety of 25 mg and 10 mg of empagliflozin in HFrEF patients.In this 3-month, single-center, open-label, randomized, positive-controlled, parallel-group study, 100 patients with HFrEF were divided into two groups, namely, groups A (n = 50) and B (n = 50), which were given 25 mg/day and 10 mg/day of empagliflozin, respectively. Cardiac function indexes at baseline and at the end of the third month were compared between the two groups, as well as adverse events during the 3-month follow-up period. The primary outcome of this study was the change in the left ventricular ejection fraction (LVEF), and the secondary outcomes were the change in the left ventricular end-diastolic diameter (LVEDD) and the incidences of hypotension, acute kidney injury (AKI), and genitourinary infections.At the end of the third month, the changes in the LVEF and LVEDD were greater in group A than those in group B (P < 0.05). During the 3-month follow-up period, the differences in the incidences of hypotension, AKI, and genitourinary infections between the two groups were statistically insignificant (P > 0.05).The results from this study suggested that 25 mg of empagliflozin might be better than 10 mg in improving heart function in HFrEF patients, and the safety profiles of 25 mg and 10 mg of empagliflozin are comparable. Further studies are expected to substantiate our speculations.

Dapagliflozin and Empagliflozin in Heart Failure with Reduced Ejection Fraction: A Retrospective Study.

Objective: Dapagliflozin 10 mg and empagliflozin 10 mg have been recommended to treat heart failure with reduced ejection fraction (HFrEF), and the purpose of this study was to compare the efficacy and safety of them in HFrEF. Methods: Two hundred and thirty-three patients with HFrEF admitted to a tertiary hospital of Zhengzhou and commenced to take dapagliflozin 10 mg/d or empagliflozin 10 mg/d were retrospectively included and separated into the dapagliflozin group (n=105) and the empagliflozin group (n=128). Their cardiac function indices before and after therapy were compared, together with the ratios of adverse events during therapy. Results: After 6 months of therapy, left ventricular ejection fraction was higher, and the ratio of New York Heart Association functional class III or IV, left ventricular end-diastolic diameter, and N-terminal pro-B-type natriuretic peptide were lower in the empagliflozin group than the dapagliflozin group (P<0.05). During 6 months of therapy, there were no statistically significant differences for the ratios of hypotension, deteriorating kidney function, and genitourinary infections between the dapagliflozin and empagliflozin groups (P>0.05). Conclusion: Despite its many limitations, this study suggested that different SGLT2 inhibitors might have differences regarding efficacy in HFrEF. We look forward to future studies to verify our conjectures.