An endogenous cholinergic system controls electrical conduction in the heart.

BACKGROUND AND AIMS: The cholinergic system is distributed in the nervous system, mediating electrical conduction through acetylcholine (ACh). This study aims to identify whether the heart possesses an intact endogenous cholinergic system and to explore its electrophysiological functions and relationship with arrhythmias in both humans and animals. METHODS: The components of the heart's endogenous cholinergic system were identified by a combination of multiple molecular cell biology techniques. The relationship of this system with cardiac electrical conduction and arrhythmias was analysed through electrophysiological techniques. RESULTS: An intact cholinergic system including ACh, ACh transmitter vesicles, ACh transporters, ACh metabolic enzymes, and ACh receptors was identified in both human and mouse ventricular cardiomyocytes (VCs). The key components of the system significantly regulated the conductivity of electrical excitation among VCs. The influence of this system on electrical excitation conduction was further confirmed both in the mice with α4 or α7 nicotinic ACh receptors (nAChRs) knockouts and in the monolayers of human induced pluripotent stem cell-derived cardiomyocytes. Mechanistically, ACh induced an inward current through nAChRs to reduce the minimum threshold current required to generate an action potential in VCs, thereby enhancing the excitability that acts as a prerequisite for electrical conduction. Importantly, defects in this system were associated with fatal ventricular arrhythmias in both patients and mice. CONCLUSIONS: This study identifies an integrated cholinergic system inherent to the heart, rather than external nerves that can effectively control cardiac electrical conduction. The discovery reveals arrhythmia mechanisms beyond classical theories and opens new directions for arrhythmia research.

Vacancy-Enhanced Sb-N4 Sites for the Oxygen Reduction Reaction and Zn-Air Battery.

With the advantages of a Fenton-inactive characteristic and unique p electrons that can hybridize with O2 molecules, p-block metal-based single-atom catalysts (SACs) for the oxygen reduction reaction (ORR) have tremendous potential. Nevertheless, their undesirable intrinsic activity caused by the closed d10 electronic configuration remains a major challenge. Herein, an Sb-based SAC featuring carbon vacancy-enhanced Sb-N4 active centers, corroborated by the results of high-angle annular dark-field scanning transmission electron microscopy and X-ray absorption fine structure, has been developed for an incredibly effective ORR. The obtained SbSA-N-C demonstrates a positive half-wave potential of 0.905 V and excellent structural stability in alkaline environments. Density functional theory calculations reveal that the carbon vacancies weaken the adsorption between Sb atoms and the OH* intermediate, thus promoting the ORR performance. Practically, the SbSA-N-C-based Zn-air batteries achieve impressive outcomes, such as a high power density of 181 mW cm-2, showing great potential in real-world applications.

Heterogeneous Rhodium Single-Atom-Site Catalyst Enables Chemoselective Carbene N-H Bond Insertion.

Transition-metal-catalyzed carbene insertion reactions of a nitrogen-hydrogen bond have emerged as robust and versatile methods for the construction of C-N bonds. While significant progress of homogeneous catalytic metal carbene N-H insertions has been achieved, the control of chemoselectivity in the field remains challenging due to the high electrophilicity of the metal carbene intermediates. Herein, we present an efficient strategy for the synthesis of a rhodium single-atom-site catalyst (Rh-SA) that incorporates a Rh atom surrounded by three nitrogen atoms and one phosphorus atom doped in a carbon support. This Rh-SA catalyst, with a catalyst loading of only 0.15 mol %, exhibited exceptional catalytic performance for heterogeneous carbene insertion with various anilines and heteroaryl amines in combination with diazo esters. Importantly, the heterogeneous catalyst selectively transformed aniline derivatives bearing multiple nucleophilic moieties into single N-H insertion isomers, while the popular homogeneous Rh2(OAc)4 catalyst produced a mixture of overfunctionalized side products. Additionally, similar selectivities for N-H bond insertion with a set of stereoelectronically diverse diazo esters were obtained, highlighting the general applicability of this heterogeneous catalysis approach. On the basis of density functional theory calculations, the observed selectivity of the Rh-SA catalyst was attributed to the insertion barriers and the accelerated proton transfer assisted by the phosphorus atom in the support. Overall, this investigation of heterogeneous metal-catalyzed carbene insertion underscores the potential of single-atom-site catalysis as a powerful and complementary tool in organic synthesis.

An evaluation of different dilution modes on circuit lifespan during continuous veno-venous hemodiafiltration without anticoagulation.

BACKGROUND: Circuit clotting remains a major problem during continuous kidney replacement therapy (CKRT), particularly in patients with contraindications to anticoagulant use. We hypothesized that the different options of alternative replacement fluid infusion sites might affect circuit lifespan. However, research-based evidence supporting an optimal replacement fluid infusion strategy is limited. Therefore, we aimed to evaluate the effect of three dilution modes (pre-dilution, post-dilution, and pre- to post-dilution) on circuit lifespan during continuous veno-venous hemodiafiltration (CVVHDF). METHODS: This prospective cohort study was conducted between December 2019 and December 2020. Patients requiring CKRT were enrolled to receive pre-dilution, post-dilution, or pre- to post-dilution fluid infusion with CVVHDF. The primary endpoint was circuit lifespan, and the secondary outcomes included the clinical parameters of patients, such as changes in serum creatinine (Scr) and blood urea nitrogen (BUN) levels, 28-day all-cause mortality, and length of stay. For all patients included in this study, only the first circuit used was recorded. RESULTS: Among the 132 patients enrolled in this study, 40 were in the pre-dilution mode, 42 were in the post-dilution mode, and 50 were in the pre- to post-dilution mode. The mean circuit lifespan was significantly longer in the pre- to post-dilution group (45.72 h, 95% CI, 39.75-51.69 h) than in the pre-dilution group (31.58 h, 95% CI, 26.33-36.82 h) and the post-dilution group (35.20 h, 95% CI, 29.62-40.78 h). There was no significant difference between the pre- and post-dilution group circuit lifespan (p > 0.05). Kaplan-Meier survival analysis revealed a significant difference between the three dilution modes (p = 0.001). No significant differences were observed in terms of changes in the Scr and BUN levels, admission day, and 28-day all-cause mortality among the three dilution groups (p > 0.05). CONCLUSION: The pre- to post-dilution mode significantly prolonged circuit lifespan but did not reduce Scr and BUN levels, compared with the pre-dilution and post-dilution modes during CVVHDF when no anticoagulants were used.

Discovery of a potent and selective covalent threonine tyrosine kinase (TTK) inhibitor.

Threonine tyrosine kinase (TTK) is a critical component of the spindle assembly checkpoint and plays a pivotal role in mitosis. TTK has been identified as a potential therapeutic target for human cancers. Here, we describe our design, synthesis and evaluation of a class of covalent TTK inhibitors, exemplified by 16 (SYL1073). Compound 16 potently inhibits TTK kinase with an IC50 of 0.016 µM and displays improved selectivity in a panel of kinases. Mass spectrometry analysis reveals that 16 covalently binds to the C604 cysteine residue in the hinge region of the TTK kinase domain. Furthermore, 16 achieves strong potency in inhibiting the growth of various human cancer cell lines, outperforming its relative reversible inhibitor, and eliciting robust downstream effects. Taken together, compound 16 provides a valuable lead compound for further optimization toward the development of drug for treatment of human cancers.

Real-Time Multi-Sensor Joint Fault Diagnosis Method for Permanent Magnet Traction Drive Systems Based on Structural Analysis.

Sensor faults are one of the most common faults that cause performance degradation or functional loss in permanent magnet traction drive systems (PMTDSs). To quickly diagnose faulty sensors, this paper proposes a real-time joint diagnosis method for multi-sensor faults based on structural analysis. Firstly, based on limited monitoring signals on board, a structured model of the system was established using the structural analysis method. The isolation and detectability of faulty sensors were analyzed using the Dulmage-Mendelsohn decomposition method. Secondly, the minimum collision set method was used to calculate the minimum overdetermined equation set, transforming the higher-order system model into multiple related subsystem models, thereby reducing modeling complexity and facilitating system implementation. Next, residual vectors were constructed based on multiple subsystem models, and fault detection and isolation strategies were designed using the correlation between each subsystem model and the relevant sensors. The validation results of the physical testing platform based on online fault data recordings showed that the proposed method could achieve rapid fault detection and the localization of multi-sensor faults in PMTDS and had a good application value.

Structural Self-Regulation-Promoted NO Electroreduction on Single Atoms.

Simultaneously elevating loading and activity of single atoms (SAs) is desirable for SA-containing catalysts, including single-atom catalysts (SACs). However, the fast self-nucleation of SAs limits the loading, and the activity is confined by the adsorption-energy scaling relationships on monotonous SAs. Here, we theoretically design a novel type of SA-containing catalyst generated by two-step structural self-regulation. In the thermodynamic self-regulation step, divacancies in graphene spontaneously pull up SAs from transition metal supports (dv-g/TM; TM = fcc Co, hcp Co, Ni, Cu), leading to the expectably high loading of SAs. The subsequent kinetic self-regulation step involving an adsorbate-assisted and reversible vacancy migration dynamically alters coordination environments of SAs, helping circumvent the scaling relationships, and consequently, the as-designed dv-g/Ni can catalyze NO-to-NH3 conversion at a low limiting potential of -0.25 V vs RHE.

Hexagonal Cobalt Nanosheets for High-Performance Electrocatalytic NO Reduction to NH3.

Electrocatalytic nitric oxide (NO) reduction not only provides an extremely promising strategy for ambient NH3 generation but also alleviates the artificially disrupted N-cycle balance. However, exploring efficient electrocatalysts to enhance the NO electroreduction performance remains a significant challenge. Herein, a hexagonal-close-packed Co nanosheet (hcp-Co) is prepared and exhibits a high NH3 yield of 439.50 µmol cm-2 h-1 and a Faraday efficiency of 72.58%, outperforming the face-centered cubic phase of the Co nanosheet (fcc-Co) and most reported electrocatalysts. Through the combination of density functional theory calculations and NO temperature-programmed desorption experiments, the superior catalytic NO reduction reaction (NORR) activity on the hcp-Co can be attributed to the unique electron structures and proton shuttle effect. A proof-of-concept device of Zn-NO batteries using the hcp-Co as the cathode is assembled and shows a power density of 4.66 mW cm-2, which is superior to the reported performance in the literature so far.

Molecular Engineering to Boost the Photo-Oxidase Activity of Molecular Rotors in Colorimetric Sensing of Temperatures.

Some organic dyes and photosensitizers with strong visible absorption can behave as photo-responsive oxidase mimics. However, the relationship between the photo-oxidase activity and molecular structure remains unclear to date. In this work, a new type of photosensitizer with the characteristics of molecular rotors, namely DPPy, served as the molecular scaffold for further investigation. To adjust the photocatalytic oxidation ability, DAPy and CBPy were designed and synthesized based on the enhancement and diminishment of the intramolecular charge transfer (ICT) process, respectively. Kinetic studies revealed that DAPy and CBPy both exhibited highly efficient photo-activated oxidase-like activity with 3,3',5,5'-tetramethylbenzidine (TMB) as the substrate, which were in good accordance with their molecular engineering to promote either type I or type II reactive oxygen species (ROS) generation. Impressively a colorimetric method based on the visible light induced oxidase-like activity of molecular rotors was developed to determine the environmental temperature for the first time. Both DAPy and CBPy showed distinct sensitivities toward temperature as compared with several molecular rotors based on the typical fluorimetric detection. This work provides a new strategy for the application of molecular rotors to overcome the non-emissive challenge in temperature sensing.

Analyzing molecular typing and clinical application of immunogenic cell death-related genes in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is considered one of the most common cancers, characterized by low early detection and high mortality rates, and is a global health challenge. Immunogenic cell death (ICD) is defined as a specific type of regulated cell death (RCD) capable of reshaping the tumor immune microenvironment by releasing danger signals that trigger immune responses, which would contribute to immunotherapy. METHODS: The ICD gene sets were collected from the literature. We collected expression data and clinical information from public databases for the HCC samples in our study. Data processing and mapping were performed using R software to analyze the differences in biological characteristics between different subgroups. The expression of the ICD representative gene in clinical specimens was assessed by immunohistochemistry, and the role of the representative gene in HCC was evaluated by various in vitro assays, including qRT-PCR, colony formation, and CCK8 assay. Lasso-Cox regression was used to screen prognosis-related genes, and an ICD-related risk model (ICDRM) was constructed. To improve the clinical value of ICDRM, Nomograms and calibration curves were created to predict survival probabilities. Finally, the critical gene of ICDRM was further investigated through pan-cancer analysis and single-cell analysis. RESULTS: We identified two ICD clusters that differed significantly in terms of survival, biological function, and immune infiltration. As well as assessing the immune microenvironment of tumors in HCC patients, we demonstrate that ICDRM can differentiate ICD clusters and predict the prognosis and effectiveness of therapy. High-risk subpopulations are characterized by high TMB, suppressed immunity, and poor survival and response to immunotherapy, whereas the opposite is true for low-risk subpopulations. CONCLUSIONS: This study reveals the potential impact of ICDRM on the tumor microenvironment (TME), immune infiltration, and prognosis of HCC patients, but also a potential tool for predicting prognosis.

One-step fabrication of high-performance graphene composites from graphite solution for bio-scaffolds and flexible strain sensors.

Graphene composites possess great application potential in various fields including flexible electrodes, wearable sensors and biomedical devices owing to their excellent mechanical and electrical properties. However, it remains challenging to fabricate graphene composites-based devices with high consistency due to the gradual aggression effect of graphene during fabrication process. Herein, we propose a method for one-step fabricating graphene/polymer composite-based devices from graphite/polymer solution by using electrohydrodynamic (EHD) printing with the Weissenberg effect (EPWE). Taylor-Couette flows with high shearing speed were generated to exfoliate high-quality graphene with a rotating steel microneedle coaxially set in a spinneret tube. The effects of the rotating speed of the needle, spinneret size and precursor ingredients on the graphene concentration were discussed. As a proof of concept, EPWE was used to successfully fabricate graphene/polycaprolactone (PCL) bio-scaffolds with good biocompatibility and graphene/thermoplastic polyurethane strain sensor for detecting human motions with a maximum gauge factor more than 2400 from 40% to 50% strain. As such, this method sheds a new light on one-stepin situfabrication of graphene/polymer composite-based devices from graphite solution with low cost.

Characterisation of kapok fibre's biochar for arsenate adsorption removal from aqueous solution.

Al-KBC was produced through the simple pyrolysis of Al-modified kapok fibres at high temperatures. Using the N2 adsorption Brunauer Emmett Teller (BET) process, Fourier transforms infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), the energy-dispersive X-ray spectroscopy (EDS) spectroscopy, and X-ray photoelectron spectroscopy (XPS), the sorbent changes and characteristics were analysed. As a result of Al's addition to the fibre's surface, Al-KBC exhibited superior As(V) adsorption performance compared to KBC due to better pore structures. Experiments on the kinetics of As(V) adsorption revealed that the adsorption followed the pseudo-second-order model and that intradiffusion was not the only factor governing the adsorption. Experiments with isotherms indicated that the adsorption mechanism corresponded to the Langmuir model, and the adsorption capacity Qm of Al-KBC at 25 °C was 483 µg/g. The thermodynamic experiments suggested that the adsorption reactions were spontaneous endothermic with a random approach at the adsorption interface. 25 mg/L of coexisting ions such as sulphate and phosphate reduced the sorbent As(V) removal ability to 65% and 39%. After seven cycles of adsorption/desorption, Al-KBC demonstrated satisfactory performance in terms of reusability, adsorbing 53% of 100 µg/L As(V) from the water. This novel BC can probably be used as a filter to purify groundwater with high As(V) concentration in the rural zone.

Comparison of antegrade robotic assisted VS laparoscopic inguinal lymphadenectomy for penile cancer.

BACKGROUND: Minimally invasive modifications of inguinal lymphadenectomy (IL), including laparoscopic IL (LIL) and robotic-assisted IL (RAIL), have been utilized for penile cancer. Comparative study is necessary to guide the decision about which minimally invasive technique to select for IL. Therefore we compared RAIL with LIL performed via an antegrade approach in terms of perioperative outcomes. METHODS: We conducted a retrospective study of 43 patients who underwent RAIL (n = 20) or LIL (n = 23) for penile cancer from 2016 to 2020. The key surgical procedures and techniques are described. Complications were graded by the Clavien-Dindo classification, and operative time, estimated blood loss (EBL), lymph nodal yield, nodal positivity, postoperative drain duration, and disease recurrence during follow-up were assessed. Categorical variables were compared using chi-squared whereas continuous variables were compared by t-tests. RESULTS: The operative time for RAIL was significantly shorter than that of LIL (median 83 vs 95 min). Significantly less blood loss was reported with RAIL than with LIL (median 10 vs 35 ml). Lymph node yield, pathological positive nodes, the hospital stay, postoperative drain duration, postoperative complications and recurrence were similar for RAIL and LIL. CONCLUSIONS: For patients with penile cancer, perioperative outcomes of RAIL and LIL were similar, but there was less blood loss, a shorter operative time for robotic cases.

Rezvilutamide versus bicalutamide in combination with androgen-deprivation therapy in patients with high-volume, metastatic, hormone-sensitive prostate cancer (CHART): a randomised, open-label, phase 3 trial.

BACKGROUND: Rezvilutamide, a novel androgen-receptor inhibitor with low blood-brain barrier penetration, has shown potent antitumour activity against metastatic castration-resistant prostate cancer. In this study, we aimed to evaluate the efficacy and safety of rezvilutamide versus bicalutamide in combination with androgen-deprivation therapy (ADT) for high-volume, metastatic, hormone-sensitive prostate cancer. METHODS: CHART is a randomised, open-label, phase 3 study done at 72 hospitals in China, Poland, Czech Republic, and Bulgaria. Eligible patients were aged 18 years or older, had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and had high-volume metastatic, hormone-sensitive prostate cancer. Previous chemotherapy or other localised treatment for prostate cancer were not allowed. Patients were randomly assigned (1:1) to receive ADT plus either rezvilutamide (240 mg) or bicalutamide (50 mg) orally once daily. Randomisation was done via an interactive response technology system (block size of four) and stratified according to ECOG performance status and presence of visceral metastasis (excluding lymph nodes). Herein, we present the results of the preplanned interim analyses for the two co-primary endpoints of radiographic progression-free survival assessed by a blinded independent review committee and overall survival in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study medication. This study is ongoing, but is closed to recruitment. This trial is registered with ClinicalTrials.gov, NCT03520478. FINDINGS: Between June 28, 2018, and Aug 6, 2020, 792 patients were screened and 654 patients were randomly assigned to receive rezvilutamide plus ADT (n=326) or bicalutamide plus ADT (n=328). At the preplanned interim analysis for radiographic progression-free survival (data cutoff May 16, 2021), the median follow-up duration was 21·2 months (IQR 16·6-25·8). Rezvilutamide significantly improved radiographic progression-free survival compared with bicalutamide (median radiographic progression-free survival not reached [95% CI not reached-not reached] vs 25·1 months [95% CI 15·7-not reached]; hazard ratio [HR] 0·44 [95% CI 0·33-0·58]; p<0·0001). At the preplanned interim analysis for overall survival (data cutoff Feb 28, 2022), the median follow-up duration was 29·3 months (IQR 21·0-33·3). Rezvilutamide significantly improved overall survival compared with bicalutamide (HR 0·58 [95% CI 0·44-0·77]; p=0·0001; median overall survival was not reached [95% CI not reached-not reached] vs not reached [36·2-not reached]). The most common grade 3 or worse adverse events of any cause in the safety population were hypertension (26 [8%] of 323 patients in the rezvilutamide group vs 24 [7%] of 324 patients in the bicalutamide group), hypertriglyceridaemia (24 [7%] vs seven [2%]), increased weight (20 [6%] vs 12 [4%]), anaemia (12 [4%] vs 16 [5%]), and hypokalaemia (11 [3%] vs four [1%]). Serious adverse events were reported in 90 (28%) of 323 patients in the rezvilutamide group and 69 (21%) of 324 patients in the bicalutamide group. No treatment-related deaths occurred in patients in the rezvilutamide group; one treatment-related death of unknown specific cause (<1%) occurred in the bicalutamide group. INTERPRETATION: In the two interim analyses, rezvilutamide plus ADT significantly improved radiographic progression-free survival and overall survival compared with bicalutamide plus ADT in patients with high-volume, metastatic, hormone-sensitive prostate cancer, with a tolerable safety profile. FUNDING: Jiangsu Hengrui Pharmaceuticals.

Comprehensive identification and expression analysis of CRY gene family in Gossypium.

BACKGROUND: The cryptochromes (CRY) are specific blue light receptors of plants and animals, which play crucial roles in physiological processes of plant growth, development, and stress tolerance. RESULTS: In the present work, a systematic analysis of the CRY gene family was performed on twelve cotton species, resulting in 18, 17, 17, 17, and 17 CRYs identified in five alloteraploid cottons (Gossypium hirsutum, G. barbadense, G. tomentosum, G. mustelinum and G. darwinii), respectively, and five to nine CRY genes in the seven diploid species. Phylogenetic analysis of protein-coding sequences revealed that CRY genes from cottons and Arabidopsis thaliana could be classified into seven clades. Synteny analysis suggested that the homoeolog of G. hirsutum Gh_A02G0384 has undergone an evolutionary loss event in the other four allotetraploid cotton species. Cis-element analysis predicated the possible functions of CRY genes in G. hirsutum. RNA-seq data revealed that Gh_D09G2225, Gh_A09G2012 and Gh_A11G1040 had high expressions in fiber cells of different developmental states. In addition, the expression levels of one (Gh_A03G0120), 15 and nine GhCRY genes were down-regulated following the PEG, NaCl and high-temperature treatments, respectively. For the low-temperature treatment, five GhCRY genes were induced, and five were repressed. These results indicated that most GhCRY genes negatively regulate the abiotic stress treatments. CONCLUSION: We report the structures, domains, divergence, synteny, and cis-elements analyses systematically of G. hirsutum CRY genes. Possible biological functions of GhCRY genes in differential tissues as well as in response to abiotic stress during the cotton plant life cycle were predicted.

Design, synthesis and structure-activity relationship studies of pyrido[2,3-d]pyrimidin-7-ones as potent Janus Kinase 3 (JAK3) covalent inhibitors.

Aberrantly activated Janus kinase 3 (JAK3) has been constantly detected in various immune disorders and hematopoietic cancers, suggesting its potential of being an attractive therapeutic target for these indications. Clinical benefits of drugs selectively targeting JAK3 versus pan-JAK inhibitors remain unclear. In this study, we report the design and synthesis of a new series of JAK3 covalent inhibitors with a pyrido[2,3-d]pyrimidin-7-one scaffold. After the extensive SAR study, compound 10f emerged to be the most potent JAK3 inhibitor with an IC50 value of 2.0 nM. It showed excellent selectively proliferation inhibitory activity against U937 cells harboring JAK3 M511I mutation, while remained weakly active to the other tested cancer cells. Compound 10f also dose-dependently inhibited the phosphorylation of JAK3 and its downstream signal STAT5 in U937 cells. Taken together, 10f may serve as a promising tool molecule for treating cancers with aberrantly activated JAK3.

Machine learning-enabled band gap prediction of monolayer transition metal chalcogenide alloys.

Monolayer transition metal dichalcogenide (TMD) alloys with tunable direct band gaps have promising applications in nanoelectronics and optoelectronics. The composition-dependent band gaps of ternary, quaternary and quinary monolayer TMD alloys have been systematically studied combining density functional theory and machine learning models in the present study. The excellent agreement between the DFT-calculated band gaps and the ML-predicted values for the training, validation and test datasets demonstrates the accuracy of our machine learning based on a neural network model. It is found that the band gap bowing parameter is closely related to the difference between the band gaps of the endpoint material compositions of the monolayer TMD alloy and increases with increasing band gap difference. The band gap bowing effects of monolayer TMD alloys obtained by mixing different transition metals are attributed to the conduction band minimum positions, while those of monolayer TMD alloys obtained by mixing different chalcogen atoms are dominated by the valence band maximum positions. This study shows that monolayer TMD alloys with tunable direct band gaps can provide new opportunities for band gap engineering, as well as electronic and optoelectronic applications.

An effector from cotton bollworm oral secretion impairs host plant defense signaling.

Insects have evolved effectors to conquer plant defense. Most known insect effectors are isolated from sucking insects, and examples from chewing insects are limited. Moreover, the targets of insect effectors in host plants remain unknown. Here, we address a chewing insect effector and its working mechanism. Cotton bollworm (Helicoverpa armigera) is a lepidopteran insect widely existing in nature and severely affecting crop productivity. We isolated an effector named HARP1 from H. armigera oral secretion (OS). HARP1 was released from larvae to plant leaves during feeding and entered into the plant cells through wounding sites. Expression of HARP1 in Arabidopsis mitigated the global expression of wounding and jasmonate (JA) responsive genes and rendered the plants more susceptible to insect feeding. HARP1 directly interacted with JASMONATE-ZIM-domain (JAZ) repressors to prevent the COI1-mediated JAZ degradation, thus blocking JA signaling transduction. HARP1-like proteins have conserved function as effectors in noctuidae, and these types of effectors might contribute to insect adaptation to host plants during coevolution.

Comparative Genomics and Functional Studies of Putative m6A Methyltransferase (METTL) Genes in Cotton.

N6-methyladenosine (m6A) RNA modification plays important regulatory roles in plant development and adapting to the environment, which requires methyltransferases to achieve the methylation process. However, there has been no research regarding m6A RNA methyltransferases in cotton. Here, a systematic analysis of the m6A methyltransferase (METTL) gene family was performed on twelve cotton species, resulting in six METTLs identified in five allotetraploid cottons, respectively, and three to four METTLs in the seven diploid species. Phylogenetic analysis of protein-coding sequences revealed that METTL genes from cottons, Arabidopsis thaliana, and Homo sapiens could be classified into three clades (METTL3, METTL14, and METTL-like clades). Cis-element analysis predicated the possible functions of METTL genes in G. hirsutum. RNA-seq data revealed that GhMETTL14 (GH_A07G0817/GH_D07G0819) and GhMETTL3 (GH_A12G2586/GH_D12G2605) had high expressions in root, stem, leaf, torus, petal, stamen, pistil, and calycle tissues. GhMETTL14 also had the highest expression in 20 and 25 dpa fiber cells, implying a potential role at the cell wall thickening stage. Suppressing GhMETTL3 and GhMETTL14 by VIGS caused growth arrest and even death in G. hirsutum, along with decreased m6A abundance from the leaf tissues of VIGS plants. Overexpression of GhMETTL3 and GhMETTL14 produced distinct differentially expressed genes (DEGs) in A. thaliana, indicating their possible divergent functions after gene duplication. Overall, GhMETTLs play indispensable but divergent roles during the growth of cotton plants, which provides the basis for the systematic investigation of m6A in subsequent studies to improve the agronomic traits in cotton.

Reliability of monitoring acid-base and electrolyte parameters through circuit lines during regional citrate anticoagulation-continuous renal replacement therapy.

BACKGROUND: The current practice involves blood sampling from the circuit line to measure acid-base and electrolyte parameters during continuous renal replacement therapy (CRRT). However, there is limited evidence supporting its reliability due to the effects of anticoagulant mechanism and access recirculation associated with regional citrate anticoagulation (RCA). AIM: To evaluate the reliability of monitoring acid-base and electrolyte parameters through circuit lines in regular and reversed connections during RCA-CRRT. STUDY DESIGN: In this prospective cohort study, we included critically ill patients receiving RCA-CRRT via a double-lumen catheter. During the second hour after CRRT initiation, we collected blood samples to monitor acid-base and electrolyte parameters and their levels were compared between samples from the circuit lines (at 0, 3, and 5 minutes) and those from the central venous catheter (CVC) line (at 0 minute). During this time, CRRT switched to the replacement state as controls. RESULTS: We observed 128 CRRT circuits in 60 adult patients receiving RCA-CRRT. Ninety-eight (76.6%) circuits had regular connections, while 30 (23.4%) had reversed connections. Among regular connections, no differences were observed in any acid-base or electrolyte parameters between samples from the CVC line and those from the circuit line at all time points (P > .05). Among reversed connections, ionized calcium levels were dramatically decreased at all three time points in samples from the circuit line compared with those from the CVC line (0.65 ± 0.12, 0.72 ± 0.11, and 0.78 ± 0.99 vs 0.98 ± 0.07 mmol/L, P < .001), with comparable levels of other acid-base or electrolyte parameters between the sampling patterns (P > .05). CONCLUSIONS: Acid-base and electrolyte parameters could be reliably monitored through the circuit line during RCA-CRRT in regular connections. However, in reversed connections, pre-filter ionized calcium concentrations determined through the circuit line were lower than those determined through the CVC line. RELEVANCE TO CLINICAL PRACTICE: We suggest sampling from arterial or CVC lines rather than from the circuit line in a reversed connection during RCA-CRRT.