The 14-3-3 protein nt GF14e interacts with CIPK2 and increases low potassium stress in tobacco.

Potassium (K+) plays a role in enzyme activation, membrane transport, and osmotic regulation processes. An increase in potassium content can significantly improve the elasticity and combustibility of tobacco and reduce the content of harmful substances. Here, we report that the expression analysis of Nt GF14e, a 14-3-3 gene, increased markedly after low-potassium treatment (LK). Then, chlorophyll content, POD activity and potassium content, were significantly increased in overexpression of Nt GF14e transgenic tobacco lines compared with those in the wild type plants. The net K+ efflux rates were severely lower in the transgenic plants than in the wild type under LK stress. Furthermore, transcriptome analysis identified 5708 upregulated genes and 2787 downregulated genes between Nt GF14e overexpressing transgenic tobacco plants. The expression levels of some potassium-related genes were increased, such as CBL-interacting protein kinase 2 (CIPK2), Nt CIPK23, Nt CIPK25, H+-ATPase isoform 2 a (AHA2a), Nt AHA4a, Stelar K+ outward rectifier 1(SKOR1), and high affinity K+ transporter 5 (HAK5). The result of yeast two-hybrid and luciferase complementation imaging experiments suggested Nt GF14e could interact with CIPK2. Overall, these findings indicate that NtGF14e plays a vital roles in improving tobacco LK tolerance and enhancing potassium nutrition signaling pathways in tobacco plants.

The management pattern and outcomes of chronic thromboembolic pulmonary hypertension: rationale and design for a Chinese real-world study.

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is a progressive pulmonary vascular disorder with substantial morbidity and mortality, also a disease underdiagnosed and undertreated. It is potentially curable by pulmonary endarterectomy (PEA) in patients with surgically accessible thrombi. Balloon pulmonary angioplasty (BPA) and targeted medical therapy are options for patients with distal lesions or persistent/recurrent pulmonary hypertension after PEA. There is an urgent need to increase the awareness of CTEPH. Qualified CTEPH centers are still quite limited. Baseline characteristics, management pattern and clinical outcome of CTEPH in China needs to be reported. METHODS AND DESIGN: The CHinese reAl-world study to iNvestigate the manaGEment pattern and outcomes of chronic thromboembolic pulmonary hypertension (CHANGE) study is designed to provide the multimodality treatment pattern and clinical outcomes of CTEPH in China. Consecutive patients who are ≥ 14 year-old and diagnosed with CTEPH are enrolled. The diagnosis of CTEPH is confirmed in right heart catheterization and imaging examinations. The multimodality therapeutic strategy, which consists of PEA, BPA and targeted medical therapy, is made by a multidisciplinary team. The blood sample and tissue from PEA are stored in the central biobank for further research. The patients receive regular follow-up every 3 or 6 months for at least 3 years. The primary outcomes include all-cause mortality and changes in functional and hemodynamic parameters from baseline. The secondary outcomes include the proportion of patients experiencing lung transplantation, the proportion of patients experiencing heart and lung transplantation, and changes in health-related quality of life. Up to 31 December 2023, the study has enrolled 1500 eligible patients from 18 expert centers. CONCLUSIONS: As a real-world study, the CHANGE study is expected to increase our understanding of CTEPH, and to fill the gap between guidelines and the clinical practice in the diagnosis, assessment and treatment of patients with CTEPH. REGISTRATION NUMBER IN CLINICALTRIALS.GOV: NCT05311072.

Assessment of a randomized controlled trial on the safety of pre-placing bronchial balloons in transbronchial lung cryobiopsy for diagnosing interstitial lung disease.

RATIONALE AND OBJECTIVES: Bleeding is a major complication of transbronchial lung cryobiopsy (TBLC), and pre-placing a bronchial balloon is one of the clinical practices used to prevent it, but with very weak evidence, which should be confirmed. This study aimed to conduct whether pre-placing a bronchial balloon in TBLC for diagnosing interstitial lung disease (ILD) is more safety. MATERIALS AND METHODS: In this prospective, single-center, randomized controlled trial, patients with suspected ILD were enrolled and randomly assigned to pre-placed balloon and none-pre-placed balloon groups. The primary outcome was incidence of moderate bleeding in each group. The secondary endpoints were the incidence of severe bleeding, pneumothorax, and other procedural complications. RESULTS: Exactly 250 patients were enrolled between August 2019 and March 2022, with 125 in each group. There were no significant differences in severe bleeding between the none-pre-placed balloon group and pre-placed balloon group (1.6% vs. 0.8%; adjusted p = 0.520), while more moderate bleeding occurred in the none-pre-placed balloon group (26.4% vs. 6.4%, adjusted p = 0.001), as well as more use of hemostatic drug (28.0% vs. 6.4%, adjusted p = 0.001). Three patients in the none-pre-placed balloon group used the bronchial balloon. More samples could be acquired in the pre-placed balloon group than in the none-pre-placed balloon group (3.8 ± 0.9 vs. 3.1 ± 0.9, p < 0.001). There were no significant differences in multidisciplinary discussion (MDD) between the two groups (89.6% vs. 91.2%, adjusted p = 0.182). CONCLUSION: A pre-placed bronchial balloon can reduce the incidence of moderate bleeding and increase the confidence of the bronchoscopists. However, it had no effect on increasing the diagnostic rate of MDD and reducing severe bleeding. REGISTRATION NUMBER: NCT04047667 ( www. CLINICALTRIALS: gov identifier).

syn-tasiRnas targeting the coat protein of potato virus Y confer antiviral resistance in Nicotiana benthamiana.

Trans-acting small interfering RNAs (tasiRNAs) are 21-nt phased (phased siRNAs) resulting from successive DCL-catalyzed processing from the end of a double-stranded RNA substrate originating from the RDR of an AGO-catalyzed cleaved RNA at a micro RNA target site. Plant tasiRNAs have been synthesized to produce synthetic tasiRNAs (syn-tasiRNAs) targeting viral RNAs that confer viral resistance. In this study, we engineered syn-tasiRNAs to target potato virus Y (PVY) infection by replacing five native siRNAs of TAS1c with 210-bp fragments from the coat protein (CP) region of the PVY genome. The results showed that the transient expression of syn-tasiR-CPpvy2 in Nicotiana benthamiana (N. benthamiana) plants conferred antiviral resistance, supported by the absence of PVY infection symptoms and viral accumulation. This indicated that syn-tasiR-CPpvy2 successfully targeted and silenced the PVY CP gene, effectively inhibiting viral infection. syn-tasiR-CPpvy1 displayed attenuated symptoms and decreased viral accumulation in these plants However, severe symptoms of PVY infection and a similar amount of viral accumulation as the control were observed in plants expressing syn-tasiR-CPpvy3. syn-tasiR-CPpvy/pvx, which targets both PVY and potato virus X (PVX), was engineered using a single precursor. After the transient expression of syn-tasiR-CPpvy/pvx3 and syn-tasiR-CPpvy/pvx5 in N. benthamiana, the plants were resistant to both PVY and PVX. These results suggested that engineered syn-tasiRNAs could not only specifically induce antiviral resistance against one target virus but could also be designed for multi-targeted silencing of different viruses, thereby preventing complex virus infection in plants.

Effect of Targeted Nursing Combined with Psychological Intervention on Chemotherapy for Gastric Carcinoma and its Influence on Patient Compliance.

Objective: To explore and analyze the effect of targeted nursing combined with psychological intervention on chemotherapy for gastric carcinoma and its influence on patient compliance. Methods: The study subjects were 88 patients diagnosed with gastric cancer and treated with chemotherapy from December 2019 to May 2021. Results: The Self-Rating Anxiety Scale and Hamilton Depression Cale scores of the study group were significantly lower than those of the control group (33.45±6.11 vs. 44.17±5.76; 35.14±5.44 vs. 46.87±5.23, respectively; P < .05); In the Morisky scale, patients in the study group scored higher than those in the control group in terms of weight control, medication compliance, appropriate exercise, and diet control; the study group had more cases of Grade 0 nausea and vomiting and significantly fewer cases of Grades I, II, III, and IV nausea and vomiting than the control group compliance (P < .05); patients in the study group gave higher scores than those in the control group on the nursing care quality, from the aspects of the quality of nursing staff. These findings highlight the significant improvements in psychological well-being, adherence to health-related behaviors, reduced nausea and vomiting, and overall satisfaction with nursing care in patients receiving targeted nursing and psychological intervention. Conclusion: The utilization of targeted nursing in tandem with psychological counseling has demonstrated a notably positive impact on chemotherapy outcomes for stomach malignancy. The amalgamation of targeted nursing and psychological intervention not only enhances patient compliance during gastric carcinoma chemotherapy but also leads to a reduction in negative emotions, decreased instances of nausea and vomiting, and higher scores for nursing quality. These findings have significant implications for clinical practice, suggesting that the integration of targeted nursing and psychological support could be a valuable approach in optimizing patient care for gastric carcinoma. The observed improvements underscore the potential for widespread adoption of this combined intervention strategy in clinical settings, potentially leading to enhanced treatment outcomes and overall patient well-being.

Origin of the neonatal gut microbiota and probiotic intervention: a randomized controlled trial.

Objective: This study aims to evaluate the origin of the neonatal gut microbiota on the 14th day and probiotic intervention in the third trimester. Methods: Samples were obtained from a total of 30 pregnant individuals and their offspring, divided into a control group with no intervention and a probiotic group with live combined Bifidobacterium and Lactobacillus tablets, analyzing by 16S rRNA amplicon sequencing of the V4 region to evaluate the composition of them. Non-metric multidimensional scaling and SourceTracker were used to evaluate the origin of neonatal gut microbiota. Results: We found that the microbiota in the neonatal gut at different times correlated with that in the maternal microbiota. The placenta had more influence on meconium microbiota. Maternal gut had more influence on neonatal gut microbiota on the 3rd day and 14th day. We also found that the maternal gut, vaginal, and placenta microbiota at full term in the probiotic group did not have a significantly different abundance of Bifidobacterium, Lactobacillus, or Streptococcus. However, some other bacteria changed in the maternal gut and their neonatal gut in the probiotic group.

Mycobacterial CpsA activates type I IFN signaling in macrophages via cGAS-mediated pathway.

Type I interferon (IFN) production is crucial in tuberculosis pathogenesis, yet the bacterial factors initiating this process are incompletely understood. CpsA, protein of Mycobacterium marinum and Mycobacterium tuberculosis, plays a key role in maintaining bacterial virulence and inhibiting host cell LC3-associated phagocytosis. By utilizing CpsA full deletion mutant studies, we re-verified its essential role in infection-induced pathology and revealed its new role in type I IFN expression. CpsA deficiency hindered IFN production in infected macrophages in vitro as well as zebrafish and mice in vivo. This effect was linked to the cGAS-TBK1-IRF3 pathway, as evidenced by decreased TBK1 and IRF3 phosphorylation in CpsA-deficient bacterial strain-infected macrophages. Moreover, we further show that CpsA deficiency cause decreased cytosolic DNA levels, correlating with impaired phagosomal membrane rupture. Our findings reveal a new function of mycobacterial CpsA in type I IFN production and offer insight into the molecular mechanisms underlying mycobacterial infection pathology.

Functional and structural dissection of glycosyltransferases underlying the glycodiversity of wolfberry-derived bioactive ingredients lycibarbarspermidines.

Lycibarbarspermidines are unusual phenolamide glycosides characterized by a dicaffeoylspermidine core with multiple glycosyl substitutions, and serve as a major class of bioactive ingredients in the wolfberry. So far, little is known about the enzymatic basis of the glycosylation of phenolamides including dicaffeoylspermidine. Here, we identify five lycibarbarspermidine glycosyltransferases, LbUGT1-5, which are the first phenolamide-type glycosyltransferases and catalyze regioselective glycosylation of dicaffeoylspermidines to form structurally diverse lycibarbarspermidines in wolfberry. Notably, LbUGT3 acts as a distinctive enzyme that catalyzes a tandem sugar transfer to the ortho-dihydroxy group on the caffeoyl moiety to form the unusual ortho-diglucosylated product, while LbUGT1 accurately discriminates caffeoyl and dihydrocaffeoyl groups to catalyze a site-selective sugar transfer. Crystal structure analysis of the complexes of LbUGT1 and LbUGT3 with UDP, combined with molecular dynamics simulations, revealed the structural basis of the difference in glycosylation selectivity between LbUGT1 and LbUGT3. Site-directed mutagenesis illuminates a conserved tyrosine residue (Y389 in LbUGT1 and Y390 in LbUGT3) in PSPG box that plays a crucial role in regulating the regioselectivity of LbUGT1 and LbUGT3. Our study thus sheds light on the enzymatic underpinnings of the chemical diversity of lycibarbarspermidines in wolfberry, and expands the repertoire of glycosyltransferases in nature.

Specific Knockout of Notch-1 in Macrophages Modulate the Progression of Hepatic Insulin Resistance in HFD Fed Mice via Regulating IRE1α-XBP1 Signals.

OBJECTIVE: To develop an intervention based on Notch-1 signalling pathway blockade by investigating the potential application of the neurogenic locus notch homologue protein 1(Notch-1) signalling pathway as a key regulator of chronic inflammation and adipogenesis in the treatment of hepatic insulin resistance (HIR). STUDY DESIGN: Experimental study. Place and Duration of the Study: Animal Laboratory of the Fourth Hospital of Hebei Medical University, Shijiazhuang, China, from April 2021 to June 2022. METHODOLOGY: HIR models were established in Notch-1WT and Notch-1MAC-KO mice by high fat diet (HFD) for 16 weeks. Haematoxylin and eosin (HE) staining and oil red O (ORO) staining were used to detect inflammatory infiltration and lipid accumulation in each group. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of TNF-α and IL-6. Free fatty acid (FFA) and total cholesterol (TC) were measured with relevant kits. Moreover, real-time quantitative polymerase chain reaction (PCR) was performed to detect the relative expressions of F4/80, Mcp1, and CD11b in hepatic tissues. Mass spectrometry was used to analyse the levels of triglyceride (TG), diacylglycerol (DAG) and conformite europeenne (CE) in liver tissue. Western blotting was used to detect the expression of related proteins. RESULTS: Specific knockdown of Notch-1 in macrophages decreases the relative fluorescence intensity of CD68 and attenuates inflammatory infiltration and lipid degeneration. There was no difference in plasma levels of FFA and TG. Specific knockdown of Notch-1 in macrophages decreases the expression of F4/80, Mcp1, and CD11b, as well as the levels of TG, DAG, CE, IL-6, and TNF-α. CONCLUSION: Specific knockout of Notch-1 in macrophages may reduce HIR by inhibiting the IRE1α-XBP1 signalling pathway. KEY WORDS: Hepatic insulin resistance, Macrophages, Notch-1, IRE1α, XBP1.

Aß1-42 stimulates an increase in autophagic activity through tunicamycin-induced endoplasmic reticulum stress in HTR-8/SVneo cells and late-onset pre-eclampsia.

Environmental changes can trigger endoplasmic reticulum (ER) stress and misfolded protein accumulation, potentially leading to pre-eclampsia (PE). Amyloid-ß (Aß) is a crucial misfolded protein that can overactivate autophagy. Our study assessed the expression of Aß1-42 and autophagic activity in PE placental tissues and trophoblasts under ER stress. Placental tissues were surgically collected from normal pregnant women (NP) and pregnant women with late-onset PE (LOPE) delivering through cesarean section. The expression levels of Aß1-42 were detected in both PE and NP placental tissues, as well as in tunicamycin (TM)-induced HTR-8/SVneo cells. Autophagy-related proteins, such as Beclin-1, the ratio of LC3-II to LC3-I, ATG5, and SQSTM1/p62 in the placental tissues and HTR-8/SVneo cells were measured by Western blot. The number and morphology of autophagosomes were observed using transmission electron microscopy (TEM). Potential targets associated with the unfolded protein response (UPR) in the placental tissues of NP and PE cases were screened using PCR Arrays. The misfolded protein was significantly upregulated in the PE group. In both PE placental tissues and TM-induced HTR-8/SVneo cells, not only was Aß1-42 upregulated, but also Beclin-1, ATG5, and LC3BII/I were significantly increased, accompanied by an increase in autophagosome count, while SQSTM1/P62 was downregulated. A total of 17 differentially expressed genes (DEGs) associated with the UPR were identified, among which elevated calnexin (CANX) was validated in the placenta from both PE and TM-induced HTR-8/SVneo cells. Autophagy is significantly upregulated in PE cases due to ER stress-induced Aß1-42 accumulation, likely mediated by autophagy-related proteins involved in the UPR.

Deficiency of P2RY11 causes narcolepsy and attenuates the recruitment of neutrophils and macrophages in the inflammatory response in zebrafish.

Purinergic receptor P2Y11, a G protein-coupled receptor that is stimulated by extracellular ATP, has been demonstrated to be related to the chemotaxis of granulocytes, apoptosis of neutrophils, and secretion of cytokines in vitro. P2Y11 mutations were associated with narcolepsy. However, little is known about the roles of P2RY11 in the occurrence of narcolepsy and inflammatory response in vivo. In this study, we generated a zebrafish P2Y11 mutant using CRISPR/Cas9 genome editing and demonstrated that the P2Y11 mutant replicated the narcolepsy-like features including reduced HCRT expression and excessive daytime sleepiness, suggesting that P2Y11 is essential for HCRT expression. Furthermore, we accessed the cytokine expression in the mutant and revealed that the P2RY11 mutation disrupted the systemic inflammatory balance by reducing il4, il10 and tgfb, and increasing il6, tnfa, and il1b. In addition, the P2RY11-deficient larvae with caudal fin injuries exhibited significantly slower migration and less recruitment of neutrophils and macrophages at damaged site, and lower expression of anti-inflammatory cytokines during tissue damage. All these findings highlight the vital roles of P2RY11 in maintaining HCRT production and secreting anti-inflammatory cytokines in the native environment, and suggested that P2RY11-deficient zebrafish can serve as a reliable and unique model to further explore narcolepsy and inflammatory-related diseases with impaired neutrophil and macrophage responses.

Photoredox Catalyzed Synthesis of gem-Difluoroalkenes and Monofluorinated Cyclooctenes via 1,5-HAT Process.

gem-Difluoroalkenes and monofluorinated cycloalkenes have emerged as basic structural units in a variety of bioactive molecules and natural products. Thus, developing straightforward and efficient methods for synthesizing fluorinated alkene compounds is of considerable significance. Herein, we disclose a visible-light-induced defluorination of 2-trifluoromethyl-1-alkene via a 1,5-HAT process using N-alkoxyphtalimides as both radical precursor and potential nucleophile. The mild and stepwise reaction leads to a variety of structurally diverse gem-difluoroalkenes and monofluorinated cyclooctenes with high efficiency, respectively.

GHG mitigation strategies on China's diverse dish consumption are key to meet the Paris Agreement targets.

Combatting climate change depends on demand-side mitigation strategies related to food, which is in turn contingent on explicit estimation and management of dish-level emissions. Here, on the basis of a bottom-up integrated emissions framework, we first estimate the greenhouse gas emissions of 540 dishes from 36 cuisines using data from over 800,488 restaurants in China's provincial capital cities. By mining residents' dietary preferences, we then design various dietary change strategies to explicitly link food emissions to the Paris Agreement pledges. The results show that China's food system greenhouse gas emissions were approximately 4.64 GtCO2eq in 2020, accounting for 37% of total emissions, with average per-dish emissions of 8.44 kgCO2eq. Current emission patterns of food consumption in China may not be consistent with the attainment of the 1.5 °C and 2 °C climate targets, but transitioning towards low-emission cuisines and dishes could change that by reducing emissions by 38-69%.

Sensitive and visual detection of SARS-CoV-2 using RPA-Cas12a one-step assay with ssDNA-modified crRNA.

BACKGROUND: CRISPR-Cas12a based one-step assays are widely used for nucleic acid detection, particularly for pathogen detection. However, the detection capability of the one-step assay is reduced because the Cas12a protein competes with the isothermal amplification enzymes for the target DNA and cleaves it. Therefore, the key to improving the sensitivity of the one-step assay is to address the imbalance between isothermal amplification and CRISPR detection. In previous study, we developed a Cas12a one-step assay using single-stranded DNA (ssDNA)-modified crRNA (mD-crRNA) and applied this method for the detection of pathogenic DNA. RESULTS: Here, we utilized mD-crRNA to establish a sensitive one-step assay that enables the visual detection of SARS-CoV-2 under ultraviolet light, achieving a detection limit of 5 aM without cross-reactivity. The sensitivity of mD-crRNA in the one-step assay was 100-fold higher than that of wild-type crRNA. Mechanistic studies revealed that the addition of ssDNA at the 3' end of mD-crRNA attenuates the binding affinity between the Cas12a-mD-crRNA complex and the target DNA. Consequently, this reduction in binding affinity decreases the cis-cleavage activity of Cas12a, mitigating its cleavage of the target DNA in the one-step assay. As a result, there is an augmentation in the amplification and accumulation of target DNA, thereby enhancing detection sensitivity. In the clinical testing of 40 SARS-CoV-2 RNA samples, the concordance between the results of the one-step assay and known qPCR results was 97.5 %. SIGNIFICANCE: The one-step assay using mD-crRNA proves to be highly sensitive and specificity and visually effective for the detection of SARS-CoV-2. Our study delves into the application of the mD-crRNA-mediated one-step assay in nucleic acid detection and its associated reaction mechanism. This holds great significance in addressing the inherent incompatibility issues between isothermal amplification and CRISPR detection.

A LAMP-based hydrogen ion selective electrochemical sensor for highly sensitive detection of Mycoplasma pneumoniae.

A concise and rapid detection method for Mycoplasma pneumoniae is urgently required due to its severe impact on human health. To meet such a need, this study proposed and constructed an innovative point-of-care testing (POCT) platform that consists of a hydrogen ion-selective loop-mediated isothermal amplification (H+-LAMP) sensor and an electrochemical detection device. The H+-LAMP sensor successfully integrated the working and reference electrodes and converted the H+ generated during the LAMP process into an electrochemical signal. High sensitivity and stability for pathogen detection were also achieved by treating the working electrode with an electrodeposited polyaniline solid contact layer and by using an ion-selective membrane. As a result, the sensor shows a sensitivity of 68.26 mV per pH, a response time of less than 2 s, and a potential drift of less than 5 mV within one hour, which well meets the urgent need. The results also demonstrated that the detection limit for Mycoplasma pneumoniae was lowered to 1 copy per µL, the nucleic acid extraction and detection process could be completed in 30 minutes, and the impact of interfering ions on the sensor was negligible. Validation with 20 clinical samples yielded satisfactory results. More importantly, the storage lifespan of such an electrochemical sensor is over seven days, which is a great advantage for on-site pathogen detection. Therefore, the hydrogen ion-selective sensor constructed in this investigation is particularly suitable as a core component for instant pathogen detection platforms.

Efficacy and safety of Chinese patent medicine combined with 5-aminosalicylic acid for patients with ulcerative colitis: A network meta-analysis of randomized controlled trials.

Objectives: Given the widespread use of Chinese patent medicines (CPMs) in combination with 5-aminosalicylic acid (5-ASA) for Ulcerative colitis (UC) patients, this study aimed to evaluate the efficacy and safety of nine CPMs combined with 5-ASA in the treatment of UC. Methods: A systematic literature search was conducted in eight databases from inception to May 2023 to identify eligible RCTs evaluating the effects of CPM combined with 5-ASA for the treatment of UC. The methodological quality of the included RCTs was assessed using the Cochrane risk of bias tool in Review Manager 5.4. The primary outcome of the meta-analysis was the overall response rate. The secondary outcomes included excellent rate, disease activity index (DAI), IL-6, IL-8, and TNF-α levels, mean platelet volume (MPV), fibrinogen (FIB) levels, recurrence rate, and adverse event rate. Network meta-analysis was performed using Review Manager 5.4 and Stata 15.0. Results: In total, 70 RCTs including 5973 patients and 10 treatment regimens were included. The combination of Kangfuxin Liquid (KFL) and 5-ASA showed the greatest efficacy in improving FIB levels and the overall response rate. Bupi Yichang Pill (BYP) combined with 5-ASA was associated with the fewest adverse events and the lowest recurrence rate. Hudi Enteric-coated Capsule (HEC) combined with 5-ASA ranked first in improving DAI. ZhiKang Capsule (ZKC), ChangYanNing Capsule (CYN), and Danshen Injection (DSI) combined with 5-ASA ranked first in improving IL-6, IL-10, and TNF-α levels, respectively. Shenling Baizhu Powder (SBP) combined with 5-ASA was associated with the highest excellent rate. Conclusions: CPM combined with 5-ASA may be more effective than 5-ASA alone for treating UC. Besides, CPM combined with 5-ASA could better reduce the recurrence rate and adverse event rate in UC patients. The current meta-analysis provides statistical evidence for clinical application.Systematic Review Registration: International Prospective Register of Systematic Reviews (PROSPERO), No. CRD42023433672.

Corrigendum: Characterization of pannexin1, connexin32, and connexin43 in spotted sea bass (Lateolabrax maculatus): they are important neuro-related immune response genes involved in inflammation-induced ATP release.

[This corrects the article DOI: 10.3389/fimmu.2022.870679.].

Transcriptional and post-transcriptional regulation of chloroplast development by nuclear-localized XAP5 CIRCADIAN TIMEKEEPER.

Chlorophyll biosynthesis and breakdown, important cellular processes for photosynthesis, occur in the chloroplast. As a semi-autonomous organelle, chloroplast development is mainly regulated by nuclear-encoded chloroplast proteins and proteins encoded by itself. However, the knowledge of chloroplast development regulated by other organelles is limited. Here, we report that the nuclear-localized XAP5 CIRCADIAN TIMEKEEPER (XCT) is essential for chloroplast development in Arabidopsis. In this study, significantly decreased chlorophyll content phenotypes of cotyledons and subsequently emerging organs from shoot apical meristem were observed in xct-2. XCT is constitutively expressed in various tissues and localized in the nuclear with speckle patterns. RNA-seq analysis identified 207 differently spliced genes and 1511 differently expressed genes, in which chloroplast development-, chlorophyll metabolism- and photosynthesis-related genes were enriched. Further biochemical assays suggested that XCT was co-purified with the well-known splicing factors and transcription machinery, suggesting dual functions of XCT in gene transcription and splicing. Interestingly, we also found that the chlorophyll contents in xct-2 significantly decreased under high temperature and high light condition, indicating XCT integrates temperature and light signals to fine-tune the chlorophyll metabolism in Arabidopsis. Therefore, our results provide new insights into chloroplast development regulation by XCT, a nuclear-localized protein, at the transcriptional and post-transcriptional level.

TTN-related hereditary myopathy with early respiratory failure presented with elevated hemoglobin initially: A case report and literature review.

Background: As common abnormal conditions in clinical practice, hypoxemia and respiratory failure are mainly caused by various respiratory diseases. However, other causes are easily overlooked but deserve more attention from doctors. Case presentation: A 44-year-old man presented with dyspnea for 10 years. In the early stage, his dyspnea was mild without hypoxemia, and he was misdiagnosed with polycythemia vera due to elevated hemoglobin level. He later developed to respiratory failure but he did not have weakness in his extremities. The positional difference in pulmonary function tests and arterial blood gas analysis led us to identify the respiratory muscle dysfunction. Fatty infiltration of the thigh muscle found by magnetic resonance imaging and muscle biopsies gave us more clues to the causes of diaphragmatic dysfunction. Finally, in combination with his family history and the results of whole exome sequencing, he was diagnosed with hereditary myopathy with early respiratory failure (HMERF, OMIM 603689) caused by a variant in the titin gene (TTN). Conclusions: We have identified a Chinese family with HMERF due to genetic variants in TTN NM_001256850.1: c.90272C > T, p. Pro30091Leu, located at g.179410829A > G on chromosome 2 (GRCh37), which may be specifically associated with the diagrammatic dysfunction. And hyperhemoglobinemia could serve as a potential sign for the early identification of HMERF.

Genetic Screening of Haploid Neural Stem Cells Reveals that Nfkbia and Atp2b4 are Key Regulators of Oxidative Stress in Neural Precursors.

Neurological diseases are expected to become the leading cause of death in the next decade. Although little is known about it, the interaction between oxidative stress and inflammation is harmful to the nervous system. To find an advanced tool for neural genetics, mouse haploid neural stem cells (haNSCs) from the somite of chimeric mouse embryos at E8.5 is established. The haNSCs present a haploid neural progenitor identity for long-term culture, promising to robustly differentiate into neural subtypes and being able to form cerebral organoids efficiently. Thereafter, haNSC mutants via a high-throughput approach and screened targets of oxidative stress is generated using the specific mutant library. Deletion of Nfkbia (the top hit among the insertion mutants) reduces damage from reactive oxygen species (ROS) in NSCs exposed to H2O2. Transcriptome analysis revealed that Atp2b4 is upregulated significantly in Nfkbia-null NSCs and is probably responsible for the observed resistance. Additionally, overexpression of Atp2b4 itself can increase the survival of NSCs in the presence of H2O2, suggesting that Atp2b4 is closely involved in this resistance. Herein, a powerful haploid system is presented to study functional genetics in neural lineages, shedding light on the screening of critical genes and drugs for neurological diseases.