Polymethoxylated flavones from the leaves of Vitex negundo have fungal-promoting and antibacterial activities during the production of broad bean koji.

Broad bean paste is a popular condiment in Asian countries. Leaves of Vitex negundo Linn. were used extensively in China during the koji-making of broad bean paste. Spreading V. negundo leaves on raw broad beans during fermentation was able to facilitate the rapid growth of fungi to form mature koji. We isolated two strains of fungi from mature koji, and four strains of bacteria from the rotten broad beans resulting from a failed attempt. According to microbial activity assays, two polymethoxylated flavones, 5-hydroxy-3,6,7,8,3',4'-hexamethoxy flavone (HJ-1) and 5,4'-dihydroxy-3,6,7,8,3'-pentamethoxy flavone (HJ-2) were isolated from V. negundo leaves, and the fungal growth promotion and inhibition of bacterial growth of these two compounds were found to improve the production of broad bean koji. This study reveals the compounds present in V. negundo leaves with bioactivity against important microbes in koji manufacture, and provides a theoretical basis for the application of V. negundo in broad bean paste production.

Efficacy and safety of low-dose esketamine for painless gastrointestinal endoscopy in adults: a systematic evaluation and meta-analysis.

Object: The benefits of low-dose esketamine for painless gastrointestinal endoscopy remain unclear. As such, the present study aimed to investigate the efficacy and safety of low-dose esketamine for this procedure. Methods: Seven common databases were searched for clinical studies investigating low-dose esketamine for painless gastrointestinal endoscopy. Subsequently, a meta-analysis was performed to synthesize and analyze the data extracted from studies fulfilling the inclusion criteria. Results: Meta-analysis revealed that, compared with propofol, low-dose esketamine in combination with propofol significantly reduced recovery time by 0.56 min (mean difference [MD] -0.56%, 95% confidence interval (CI) -1.08 to -0.05, p = 0.03), induction time by 9.84 s (MD -9.84, 95% CI -12.93 to -6.75, p < 0.00001), propofol dosage by 51.05 mg (MD -51.05, 95% CI -81.53 to -20.57, p = 0.01), and increased mean arterial pressure by 6.23 mmHg (MD 6.23, 95% CI 1.37 to 11.08, p = 0.01). Meanwhile, low-dose esketamine reduced injection pain by 63% (relative risk [RR] 0.37, 95% CI 0.28 to 0.49, p < 0.00001), involuntary movements by 40% (RR 0.60, 95% Cl 0.42 to 0.85, p < 0.005), choking by 42% (RR 0.58, 95% Cl 0.38 to 0.88, p = 0.01), bradycardia by 68% (RR 0.32, 95% Cl 0.18 to 0.58, p = 0.0002), hypotension by 71% (RR 0.29, 95% Cl 0.21 to 0.40, p < 0.00001), respiratory depression by 63% (RR 0.37, 95% 0.26 to 0.51, p < 0.00001), additional cases of propofol by 53% (RR 0.47, 95% Cl 0.29 to 0.77, p = 0.002), and increased hypertension by 1000% (RR 11.00, 95% Cl 1.45 to 83.28, p = 0.02). There were no significant differences in mean heart rate, mean oximetry saturation, delirium, dizziness, vomiting, tachycardia, and hypoxemia. Subgroup analyses revealed that, compared with other dose groups, 0.25 mg/kg esketamine afforded additional benefits in recovery and induction time, mean arterial pressure, involuntary movements, hypoxemia, and respiratory depression. Conclusion: Low-dose esketamine was found to be safe and effective for providing anesthesia during gastrointestinal endoscopy, with 0.25 mg/kg identified as the optimal dose within the dosage ranges examined. However, caution should be exercised when administering this drug to patients with inadequate preoperative blood pressure control.

Nematicidal Activity of 20-Deoxyingenol-3-angelate from Euphorbia peplus Latex Through Protein Kinase C Isotype TPA-1.

The latex of Euphorbia peplus and its major component 20-deoxyingenol-3-angelate (DI3A) displayed significant nematicidal activity against Caenorhabditis elegans and Panagrellus redivivus. DI3A treatment inhibited the growth and development of nematodes and caused significantly negative effects on locomotion behavior, reproduction, and accumulation of reactive oxygen species. Transcriptome analysis indicated that differential expression genes in DI3A-treated C. elegans were mainly associated with the metabolism, growth, and development process, which were further confirmed by RT-qPCR experiments. The expression level of TPA-1 gene encoding a protein kinase C isotype was obviously upregulated by DI3A treatment, and knockdown of TPA-1 by RNAi technology in the nematode could relieve the growth-inhibitory effect of DI3A. Metabolic analysis indicated that DI3A was hardly metabolized by C. elegans, but a glycosylated indole derivative was specifically accumulated likely due to the activation of detoxification. Overall, our findings suggested that DI3A from E. peplus latex exerted a potent nematicidal effect through the gene TPA-1, which provides a potential target for the control of nematodes and also suggests the potential application value of E. peplus latex and DI3A as botanical nematicides.

A novel contact force sensing pulsed field ablation catheter in a porcine model.

BACKGROUND: Pulsed field ablation (PFA) has emerged as a novel non-thermal modality with highly myocardium-specific. However, the PFA catheter based on contact force (CF)-sensing has not been reported. The study aimed to evaluate the efficacy and safety of a novel CF-sensing PFA catheter. METHODS: First, different CF (5, 15, 25, and 35 g) of the novel PFA catheter were evaluated on lesion dimensions during ablation on right and left ventricle in two pigs. Next, this catheter was further evaluated on four typical sites of superior vena cava (SVC), cavotricuspid isthmus (CTI), right superior pulmonary vein (RSPV), and right inferior pulmonary vein (RIPV) for atrial ablation in another six pigs. Electrical isolation was evaluated immediately after ablation and 30-day survival. Chronic lesions were assessed via histopathology after euthanasia. Acute and chronic safety outcomes were observed peri- and post-procedurally. RESULTS: In ventricular ablation, increased CF from 5 to 15 g produced significantly greater lesion depth but nonsignificant increases from 15 to 35 g. In atrial ablation, the novel CF-sensing PFA deliveries produced an acute attenuation of local electrograms and formation of a continuous line of block in all 6 pigs. The ablation line remained sustained blockage at the 30-day survival period. The CF of SVC, CTI, RSPV, and RIPV was 9.4 ± 1.5, 14.5 ± 3.2, 17.2 ± 2.6, and 13.4 ± 2.8 g, respectively. Moreover, no evidence of damage to esophagus or phrenic nerve was observed. CONCLUSION: The novel CF-sensing PFA catheter potentiated efficient, safe, and durable ablation, without causing damage to the esophagus or phrenic nerve.

Exosomes Derived from Astragaloside IV-pretreated Endothelial Progenitor Cells (AS-IV-Exos) Alleviated Endothelial Oxidative Stress and Dysfunction Via the miR-210/ Nox2/ROS Pathway.

BACKGROUND: Chronic hyperglycemia in diabetes induces oxidative stress, leading to damage to the vascular system. In this study, we aimed to evaluate the effects and mechanisms of AS-IV-Exos in alleviating endothelial oxidative stress and dysfunction caused by high glucose (HG). METHODS: Histopathological changes were observed using HE staining, and CD31 expression was assessed through immunohistochemistry (IHC). Cell proliferation was evaluated through CCK8 and EDU assays. The levels of ROS, SOD, and GSH-Px in the skin tissues of each group were measured using ELISA. Cell adhesion, migration, and tube formation abilities were assessed using adhesion, Transwell, and tube formation experiments. ROS levels in HUVEC cells were measured using flow cytometry. The levels of miR-210 and Nox2 were determined through quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The expression of Nox2, SOD, GSH-Px, CD63, and CD81 was confirmed using WB. RESULTS: The level of miR-210 was reduced in diabetes-induced skin damage, while the levels of Nox2 and ROS increased. Treatment with AS-IV increased the level of miR-210 in EPC-Exos. Compared to Exos, AS-IV-Exos significantly reduced the proliferation rate, adhesion number, migration speed, and tube-forming ability of HGdamaged HUVEC cells. AS-IV-Exos also significantly decreased the levels of SOD and GSH-Px in HG-treated HUVEC cells and reduced the levels of Nox2 and GSH-Px. However, ROS levels and Nox2 could reverse this effect. CONCLUSION: AS-IV-Exos effectively alleviated endothelial oxidative stress and dysfunction induced by HG through the miR-210/Nox2/ROS pathway.

Astragaloside IV (ASIV) Mediates Endothelial Progenitor Cell (EPC) Exosomal LINC01963 to Inhibit Pyroptosis and Oxidative Stress in High Glucose-impaired Endothelial Cells.

BACKGROUND: Hyperglycemia is widespread in the world's population, increasing the risk of many diseases. This study aimed to explore the regulatory effect and mechanism of astragaloside IV (ASIV)-mediated endothelial progenitor cells (EPCs) exosomal LINC01963 in endothelial cells (HUVECs) impaired by high glucose. METHODS: Morphologies of exosomes were observed by light microscope and electron microscope. Immunofluorescence was used to identify EPCs and detect the expressions of caspase-1. LINC01963 was detected by quantitative reverse transcription PCR. NLRP3, ASC, and caspase-3 were detected by Western Blot. Nanoparticle tracking analysis was carried out to analyze the exosome diameter. High-throughput sequencing was applied to screen target lncRNAs. The proliferation of endothelial cells was measured by cell counting kit-8 assay. The apoptosis level of HUVECs was detected by flow cytometry and TdT-mediated dUTP Nick-End labeling. The levels of IL- 1ß, IL-18, ROS, SOD, MDA, and LDH were measured by enzyme-linked immunosorbent assay. RESULTS: ASIV could promote the secretion of the EPC exosome. LINC01963 was obtained by high-throughput sequencing. It was observed that high glucose could inhibit the proliferation, reduce the level of SOD, the expression of NLRP3, ASC, and caspase- 1, increase the levels of IL-1ß, IL-18, ROS, MDA, and LDH, and promote apoptosis of HUVECs. Whereas LINC01963 could inhibit the apoptosis of HUVECs, the increase the expression of NLRP3, ASC, and caspase-1, and decrease the levels of IL-1ß, IL-18, ROS, MDA, and LDH. CONCLUSION: EPCs exosomal LINC01963 play an inhibitory role in high glucoseinduced pyroptosis and oxidative stress of HUVECs. This study provides new ideas and directions for treating hyperglycemia and researching exosomal lncRNAs.

A new C19-diterpenoid alkaloid in Aconitum georgei Comber.

Nine diterpenoid alkaloids were isolated from Aconitum georgei Comber belonging to the genus Aconitum in Ranunculaceae family. Their structures were determinated by using HR-ESI-MS and 1 D/2D NMR spectra as geordine (1), yunaconitine (2), chasmanine (3), crassicauline A (4), forestine (5), pseudaconine (6), 14-acetylalatisamine (7), austroconitine B (8), and talatisamine (9). Among them, compound 1 is a previously undescribed aconitine-type C19-diterpenoid alkaloid, and compounds 3, and 5-9 have not previously been isolated from this species. The results of in vitro experiments indicated that new compound 1 possesses mild anti-inflammatory activity, which inhibited the production of NO in LPS-activated RAW 264.7 cells with an inhibition ratio of 29.75% at 50 µM.

Chemical Structure Diversity and Extensive Biological Functions of Specialized Metabolites in Rice.

Rice (Oryza sativa L.) is thought to have been domesticated many times independently in China and India, and many modern cultivars are available. All rice tissues are rich in specialized metabolites (SPMs). To date, a total of 181 terpenoids, 199 phenolics, 41 alkaloids, and 26 other types of compounds have been detected in rice. Some volatile sesquiterpenoids released by rice are known to attract the natural enemies of rice herbivores, and play an indirect role in defense. Momilactone, phytocassane, and oryzalic acid are the most common diterpenoids found in rice, and are found at all growth stages. Indolamides, including serotonin, tryptamine, and N-benzoylserotonin, are the main rice alkaloids. The SPMs mainly exhibit defense functions with direct roles in resisting herbivory and pathogenic infections. In addition, phenolics are also important in indirect defense, and enhance wax deposition in leaves and promote the lignification of stems. Meanwhile, rice SPMs also have allelopathic effects and are crucial in the regulation of the relationships between different plants or between plants and microorganisms. In this study, we reviewed the various structures and functions of rice SPMs. This paper will provide useful information and methodological resources to inform the improvement of rice resistance and the promotion of the rice industry.

Prognostic Role of Mitochondrial Transcription Termination Factor 3 in Thyroid Carcinoma.

Background: Studies have shown that the Mitochondrial Transcription Termination Factor 3 (MTERF3) negatively regulates mitochondrial gene expression and energy metabolism, and plays a significant role in many cancer types. Nevertheless, the expression and prognostic role of MTERF3 in patients with thyroid carcinoma (THCA) is still unclear. Thus, we investigated the expression, clinicopathological significance, and prognostic value of MTERF3 in THCA. Methods: The protein and mRNA expression levels of MTERF3 were, respectively, analyzed using immunohistochemistry (IHC) from THCA tissues and RNA-Seq data downloaded from The Cancer Genome Atlas. In addition, the relationships among the expression of MTERF3, the stemness feature, the extent of immune infiltration, drug sensitivity, the expression of ferroptosis, and N6-methyladenosine (m6A) methylation regulators, were evaluated as prognostic indicators for patients with THCA using the Kaplan-Meier plotter database. Results: The IHC and RNAseq results showed that the protein and mRNA expression levels of MTERF3 in adjacent nontumor tissues were significantly higher than in THCA tissues. The survival analysis indicated that decreased expression of MTERF3 was associated with a poorer prognosis. Furthermore, the expression of MTERF3 not only negatively correlated with the enhancement of the stemness of THCA and the reduction of drug sensitivity but also was implicated in ferroptosis and m6A methylation. Conclusion: The data from this study support the hypothesis that decreased expression of MTERF3 in THCA is associated with a poor prognosis.

The discriminatory diagnostic value of multimodal ultrasound combined with blood cell analysis for granulomatous lobular mastitis and invasive ductal carcinoma of the breast.

OBJECTIVE: To explore the discriminatory diagnostic value of multimodal ultrasound(US) combined with blood cell analysis(BCA) for Granulomatous Lobular Mastitis (GLM) and Invasive Ductal Carcinoma(IDC) of the breast. METHODS: A total of 157 breast disease patients were collected and divided into two groups based on postoperative pathological results: the GLM group(57 cases with 57 lesions) and the IDC group(100 cases with 100 lesions). Differences in multimodal ultrasound features and the presence of BCA were compared between the two groups. The receiver operating characteristic(ROC) curve was used to calculate the optimal cutoff values, sensitivity, specificity, 95% confidence interval(CI), and the area under the curve(AUC) for patient age, lesion size, lesion resistive index(RI), and white blood cell(WBC) count in BCA. Sensitivity, specificity, positive predictive value, negative predictive value, diagnostic accuracy, and AUC were calculated for different diagnostic methods. RESULTS: There were statistically significant differences(P <  0.05) observed between GLM and IDC patients in terms of age, breast pain, the factors in Conventional US(lesion size, RI, nipple delineation, solitary/multiple lesions, margin, liquefaction area, growth direction, microcalcifications, posterior echogenicity and abnormal axillary lymph nodes), the factors in CEUS(contrast agent enhancement intensity, enhancement pattern, enhancement range, and crab-like enhancement) and the factors in BCA(white blood cells, neutrophils, lymphocytes and monocytes). ROC curve analysis results showed that the optimal cutoff values for distinguishing GLM from IDC were 40.5 years for age, 7.15 cm for lesion size, 0.655 for lesion RI, and 10.525*109/L for white blood cells. The diagnostic accuracy of conventional US combined with CEUS(US-CEUS) was the highest(97.45%). The diagnostic performance AUCs for US-CEUS, CEUS, and US were 0.965, 0.921 and 0.832, respectively. CONCLUSION: Multifactorial analysis of multimodal ultrasound features and BCA had high clinical application value in the differential diagnosis of GLM and IDC.

Gold(I)-Organic Frameworks as Catalysts for Carboxylation of Alkynes with CO2.

Construction of gold-based metal-organic frameworks (Au-MOFs) would bring the merits of gold chemistry into MOFs. However, it still remains challenging because gold cations are easily reduced to metallic gold under solvothermal conditions. Herein, we present the first example of Au-MOFs prepared from the networking of cyclic trinuclear gold(I) complexes by formal transimination reaction in a rapid (<15 min) and scalable (up to 1 g) fashion under ambient condition. The Au-MOFs feature uniform porosity, high crystallinity, and superior chemical stability toward base (i.e., 20 M NaOH). With open Au(I) sites in the skeleton, the Au-MOFs as heterogeneous catalysts delivered good performance and substrate tolerance for the carboxylation reactions of alkynes with CO2. This work demonstrates a facile approach to reticularly synthesize Au-MOFs by combining the coordination and dynamic covalent chemistry.

Comparison of the diagnostic performance of three ultrasound thyroid nodule risk stratification systems for follicular thyroid neoplasm: K-TIRADS, ACR -TIRADS and C-TIRADS.

OBJECTIVE: To explore the diagnostic performance of the currently used ultrasound-based thyroid nodule risk stratification systems (K-TIRADS, ACR -TIRADS, and C-TIRADS) in differentiating follicular thyroid adenoma (FTA) from follicular thyroid carcinoma (FTC). METHODS: Clinical data and preoperative ultrasonographic images of 269 follicular thyroid neoplasms were retrospectively analyzed. All of them were detected by Color Doppler ultrasound instruments equipped with high-frequency liner array probes (e.g. Toshiba Apoli500 with L5-14MHZ; Philips IU22 with L5-12MHZ; GE LOGIQ E9 with L9-12MHZ and MyLab Class C with L9-14MHZ). The diagnostic performance of three TIRADS classifications for differentiating FTA from FTC was evaluated by drawing the receiver operating characteristic (ROC) curves and calculating the cut-off values. RESULTS: Of the 269 follicular neoplasms (mean size, 3.67±1.53 cm), 209 were FTAs (mean size, 3.56±1.38 cm) and 60 were FTCs (mean size, 4.07±1.93 cm). There were significant differences in ultrasound features such as margins, calcifications, and vascularity of thyroid nodules between the FTA and FTC groups (P < 0.05). According to the ROC curve comparison analysis, the diagnostic cut-off values of K-TIRADS, ACR-TIRADS, and C-TIRADS for identifying FTA and FTC were K-TR4, ACR-TR4, and C-TR4B, respectively, and the areas under the curves were 0.676, 0.728, and 0.719, respectively. The difference between ACR-TIRADS and K-TIRADS classification was statistically significant (P = 0.0241), whereas the differences between ACR-TIRADS and C-TIRADS classification and between K-TIRADS and C-TIRADS classification were not statistically significant (P > 0.05). CONCLUSION: The three TIRADS classifications were not conducive to distinguishing FTA from FTC. It is necessary to develop a novel malignant risk stratification system specifically for the identification of follicular thyroid neoplasms.

Functional disruptions of the brain network in low back pain: a graph-theoretical study.

PURPOSE: The aim of this study was to investigate alterations in the topological organization of whole-brain functional networks in patients with chronic low back pain (CLBP) and characterize the relationship of these alterations with pain characteristics. METHODS: Thirty-three CLBP patients and 34 matched healthy controls (HCs) underwent fMRI scans. A graph-theoretical approach was applied to identify brain network changes in patients suffering from chronic low back pain given its nonspecific etiology and complexity. Graph theory-based analysis was used to construct functional connectivity matrices and extract the features of small-world networks of the brain in both groups. Then, the whole-brain functional connectivity differences were characterized by network-based statistics (NBS) analysis, and the relationship between the altered brain features and clinical measures was explored. RESULTS: At the global level, patients with CLBP showed significantly decreased gamma, sigma, global efficiency, and local efficiency and increased lambda and shortest path length compared with HCs. At the regional level, there were deficits in nodal efficiency within the default mode network and salience network. NBS analysis demonstrated that decreased functional connectivity was present in the CLBP patients, mainly in the frontolimbic circuit and temporal regions. Furthermore, aspects of topological dysfunctions in CLBP were correlated with pain severity. CONCLUSION: This study highlighted the aberrant topological organization of functional brain networks in CLBP, which may shed light on the pathophysiology of CLBP and support the development of pain management approaches.

Esterification with a Long-Chain Fatty Acid Elevates the Exposure Toxicity of Tigliane Diterpenoids from Euphorbia fischeriana Roots against Nematodes.

In this study, two tigliane diterpenoids, 12-deoxyphorbol-13-hexadecanoate and 12-deoxyphorbol-13-acetate (prostratin), were identified from the methanol extract of the roots of Euphorbia fischeriana and were found to have the ability to significantly reduce the survival of Caenorhabditis elegans. It was determined that exposure to these two compounds had toxic effects on the growth, reproduction, locomotion behavior, and accumulation of lipids and lipofuscin of the nematodes. Moreover, the transcription levels of the genes associated with lipid accumulation, apoptosis, insulin, and nuclear hormone synthesis in C. elegans were significantly influenced. Interestingly, 12-deoxyphorbol-13-hexadecanoate produced exposure toxicity at lower concentrations than that of prostratin. Pearson correlation analysis indicates that the elevated exposure toxicity of 12-deoxyphorbol-13-hexadecanoate may be the result of differing transcription levels, which result from the differential expression of fat-6, egl-38, and cep-1. These results reveal that esterification with a long-chain fatty acid elevates the exposure toxicity of this tigliane diterpenoid, thus providing a basis for the application of tigliane diterpenoids in plant-derived nematicides.

Altered habenular connectivity in chronic low back pain: An fMRI and machine learning study.

The habenula has been implicated in the pathogenesis of pain and analgesia, while evidence concerning its function in chronic low back pain (cLBP) is sparse. This study aims to investigate the resting-state functional connectivity (rsFC) and effective connectivity of the habenula in 52 patients with cLBP and 52 healthy controls (HCs) and assess the feasibility of distinguishing cLBP from HCs based on connectivity by machine learning methods. Our results indicated significantly enhanced rsFC of the habenula-left superior frontal cortex (SFC), habenula-right thalamus, and habenula-bilateral insular pathways as well as decreased rsFC of the habenula-pons pathway in cLBP patients compared to HCs. Dynamic causal modelling revealed significantly enhanced effective connectivity from the right thalamus to right habenula in cLBP patients compared with HCs. RsFC of the habenula-SFC was positively correlated with pain intensities and Hamilton Depression scores in the cLBP group. RsFC of the habenula-right insula was negatively correlated with pain duration in the cLBP group. Additionally, the combination of the rsFC of the habenula-SFC, habenula-thalamus, and habenula-pons pathways could reliably distinguish cLBP patients from HCs with an accuracy of 75.9% by support vector machine, which was validated in an independent cohort (N = 68, accuracy = 68.8%, p = .001). Linear regression and random forest could also distinguish cLBP and HCs in the independent cohort (accuracy = 73.9 and 55.9%, respectively). Overall, these findings provide evidence that cLBP may be associated with abnormal rsFC and effective connectivity of the habenula, and highlight the promise of machine learning in chronic pain discrimination.

Caterpillars Detoxify Diterpenoid from Nepeta stewartiana by the Molting Hormone Gene CYP306A1.

Herbivorous insects are well known for detoxifying a broad range of the defense compounds produced by the plants that they feed on, but knowledge of the mechanisms of detoxification is still very limited. Here, we describe a system in which two species of lepidopteran caterpillars metabolize an abietane diterpene from the plants of Nepeta stewartiana Diels to an oxygenated derivative that is less active biologically. We found that this transformation could be catalyzed by a cytochrome P450 enzyme in caterpillars, which are associated with molting. Most interestingly, abietane diterpene targets the molting-associated gene CYP306A1 to alter the content of molting hormones in the insect at specific developmental stages and competitively inhibit molting hormone metabolism. These findings identify the mechanism by which caterpillars are able to detoxify abietane diterpenoid through hydroxylation at the C-19 position, which may be opening up exciting research questions into the mechanisms of interaction between plants and insects.

"Challenges" During Leadless Pacemaker Implantation.

Leadless pacemaker (LP) is a new type of pacemaker that integrates generator and leads, and has become an effective alternative to traditional transvenous pacemakers. It can be used for difficult or complicated situations of traditional pacemaker implantation, such as subclavian vein occlusion, traditional pacemaker pocket infection, lead fracture, and multiple pacemaker replacements. Because no pockets and leads are required, LPs eliminate pocket- and lead-related complications compared to traditional pacemakers. Multiple studies have demonstrated its reliable safety and efficacy. Compared with traditional pacemakers, due to the different implantation methods, the difficulties encountered during the implantation process are also different. This article reviews the difficulties that may be encountered during leadless implantation and looks forward to the future of leadless pacemakers.

Homozygous frameshift variant in POC1B causes male infertility with oligoasthenoteratozoospermia in human and mice.

Several different mutations in the proteome of centriole 1 centriolar protein B (POC1B) have been linked to cone dystrophy or cone-rod dystrophy (CORD). However, mutations in POC1B that are associated with both CORD and oligoasthenoteratozoospermia (OAT) have not been reported previously. Here, whole-exome sequencing was performed to identify a homozygous frameshift variant (c.151delG) in POC1B in the two brothers who had been diagnosed with both CORD and OAT from a consanguineous family. Transcript and protein analyses of biological samples from the two patients carrying the variant showed that POC1B protein is lost in sperm cells. The system CRISPR/Cas9 was utilized to create poc1bc.151delG/c.151delG knock-in (KI) mice. Notably, poc1bc.151delG/c.151delG KI male mice presented with OAT phenotype. Additionally, testicular histology and transmission electron microscopy analysis of the testes and sperm indicated that Poc1b mutation results in abnormal formation of acrosomes and flagella. Collectively, according to our experimental data on human volunteers and animal models, biallelic mutations in POC1B can cause OAT and CORD in mice and humans.

A new perspective on plant defense against foliar gall-forming aphids through activation of the fruit abscission pathway.

The peach aphid Tuberocephalus momonis seriously damages leaves and forms galls in the peach species Prunus persica f. rubro-plena, P. persica, and P. davidiana. Leaves bearing galls formed by these aphids will be abscised at least two months earlier than the healthy leaves on the same tree. Thus, we hypothesize that gall development is likely to be governed by phytohormones involved in normal organogenesis. The soluble sugar content was positively correlated between gall tissues and fruits, suggesting that the galls are sink organs. The results of UPLC-MS/MS analysis showed that higher concentrations of 6-benzylaminopurine (BAP) accumulated in both the gall-forming aphids, the galls themselves and the fruits of peach species than in healthy leaves, suggesting that BAP was being synthesized by the insects to stimulate the establishment of a gall. A significant increase in the concentrations of abscisic acid (ABA) in fruits and jasmonic acid (JA) in gall tissues indicated that these plants are defending from the galls. The concentrations of 1-amino-cyclopropane-1-carboxylic acid (ACC) significantly increased in gall tissues compared with healthy leaves, and were positively correlated with both fruit and gall development. In addition, transcriptome sequencing analysis revealed that during gall abscission, differentially expressed genes in both 'ETR-SIMKK-ERE1' and 'ABA-PYR/PYL/RCAR-PP2C-SnRK2' were significantly enriched during gall abscission. Our results showed that ethylene pathway was involved in the abscission of gall, and this gall abscission allowed the host plants to protect themselves from the gall-forming insects, at least partially.

Defensive Specialized Metabolites from the Latex of Euphorbia jolkinii.

Plant latex is sequestered in laticiferous structures and exuded immediately from damaged plant tissues. The primary function of plant latex is related to defense responses to their natural enemies. Euphorbia jolkinii Boiss. is a perennial herbaceous plant that greatly threaten the biodiversity and ecological integrity of northwest Yunnan, China. Nine triterpenes (1-9), four non-protein amino acids (10-13) and three glycosides (14-16) including a new isopentenyl disaccharide (14), were isolated and identified from the latex of E. jolkinii. Their structures were established on the basis of comprehensive spectroscopic data analyses. Bioassay revealed that meta-tyrosine (10) showed significant phytotoxic activity, inhibiting root and shoot growth of Zea mays, Medicago sativa, Brassica campestris, and Arabidopsis thaliana, with EC50 values ranging from 4.41 ± 1.08 to 37.60 ± 3.59 µg/mL. Interestingly, meta-tyrosine inhibited the root growth of Oryza sativa, but promoted their shoot growth at the concentrations below 20 µg/mL. meta-Tyrosine was found to be the predominant constituent in polar part of the latex extract from both stems and roots of E. jolkinii, but undetectable in the rhizosphere soil. In addition, some triterpenes showed antibacterial and nematicidal effects. The results suggested that meta-tyrosine and triterpenes in the latex might function as defensive substances for E. jolkinii against other organisms.