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Abstract N6-methyladenosine (m6A) methylation is the most universal internal modification in eukaryotic mRNA. With elaborate functions executed by m6A writers, erasers, and readers, m6A modulation is involved in myriad physiological and pathological processes. Extensive studies have demonstrated m6A modulation in diverse tumours, with effects on tumorigenesis, metastasis, and resistance. Recent evidence has revealed an emerging role of m6A modulation in tumour immunoregulation, and divergent m6A methylation patterns have been revealed in the tumour microenvironment. To depict the regulatory role of m6A methylation in the tumour immune microenvironment (TIME) and its effect on immune evasion, this review focuses on the TIME, which is characterized by hypoxia, metabolic reprogramming, acidity, and immunosuppression, and outlines the m6A-regulated TIME and immune evasion under divergent stimuli. Furthermore, m6A modulation patterns in anti-tumour immune cells are summarized.

ObjectiveThis paper aims to review the current evidence on electroacupuncture as an effective and safe therapy for cancer pain management.MethodsFive databases were searched from their inception through November 11, 2022. Only the randomized controlled trials that meet the eligibility criteria were finally included in the study. Literature screening and data extraction were performed independently by two reviewers, and RevMan 5.3 used for meta-analysis.ResultsA total of 17 RCTs met our inclusion criteria. We used 8 indicators to estimate the meta-analysis results, most of which proved statistically significant, including VAS scores, NRS scores, and KPS scores. To be specific, VAS scores (MD = −1.41, 95% CI: −2.42 to −0.41, P = 0.006) and NRS scores (MD = −1.19, 95% CI: −1.72 to −0.66, P

BackgroundThere is a crosstalk between traditional Chinese medicine (TCM) and gut microbiota (GM), many articles have studied and discussed the relationship between the two. The purpose of this study is to use bibliometric analysis to explore the research status and development trends of the TCM/GM research, identify and analyze the highly cited papers relating to the TCM/GM.MethodsA literature search regarding TCM/GM publications from 2004 to 2021 was undertaken on August 13, 2022. The main information (full record and cited references) of publications was extracted from the Science Citation Index Expanded (SCI-E) of Web of Science Core Collection (WoSCC). The Bibliometrix of R package, CiteSpace and VOSviewer were used for bibliometric analysis.ResultsA total of 830 papers were included. The publication years of papers were from 2004 to 2021. The number of papers had increased rapidly since 2018. China had the most publications and made most contributions to this field. Nanjing University of Chinese Medicine and Beijing University of Chinese Medicine were in the leading productive position in TCM/GM research, Chinese Academy of Chinese Medical Sciences had the highest total citations (TC). Duan Jin-ao from Nanjing University of Chinese Medicine had the largest number of publications, and Tong Xiao-lin from China Academy of Chinese Medical Sciences had the most TC. The Journal of Ethnopharmacology had the most published papers and the most TC. The main themes in TCM/GM included the role of GM in TCM treatment of glucolipid metabolism diseases and lower gastrointestinal diseases; the mechanism of interactions between GM and TCM to treat diseases; the links between TCM/GM and metabolism; and the relationship between GM and oral bioavailability of TCM.ConclusionThis study gained insight into the research status, hotspots and trends of global TCM/GM research, identified the most cited articles in TCM/GM and analyzed their characteristics, which may inform clinical researchers and practitioners’ future directions.

BackgroundThere is a crosstalk between gut microbiota (GM) and cancer immunotherapy (CI). The purpose of this study is to use bibliometric analysis to identify the highly cited papers relating to GM/CI and explore the research status and development trends of the GM/CI research.MethodsA literature search regarding GM/CI publications from 2012 to 2021 was undertaken on July 4, 2022. The article titles, journals, authors, institutions, countries, total citations, keywords, and other information were extracted from the Science Citation Index Expanded (SCIE) of Web of Science Core Collection (WoSCC). The Bibliometrix of R package and VOSviewer were used for bibliometric analysis.ResultsA total of 665 papers were extracted. The number of papers has increased rapidly over the past decade, especially after 2018. The United States and China had the most publications and made great contributions to this field. Th5e Univ Texas MD Anderson Canc Ctr and Univ Paris Saclay were absolutely in the leading position in GM/CI. The most influential authors were Zitvogel L and Routy B. Frontiers in Immunology had the most publications and Science had the most total citations. Historical direct citation analysis explained the historical evolution in GM/CI. Highly cited papers and high-frequency keywords illustrated the current status and trends of GM/CI. Four clusters were identified and the important topics included the role of GM and antibiotics in CI, the methods of targeting GM to improve CI outcomes, the mechanism by which GM affects CI and the application of ICIs in melanoma. “Tumor microbiome”, “proton pump inhibitors” and “prognosis” may be the new focus of attention in the next few years.ConclusionThis study filtered global publications on GM/CI correlation and analyzed their bibliometric characteristics, identified the most cited papers in GM/CI, and gained insight into the status, hotspots and trends of global GM/CI research, which may inform researchers and practitioners of future directions.

The immunohistochemical definition of estrogen/progesterone receptors dictates endocrine feasibility in the treatment course of breast cancer. Characterized by the deficiency of estrogen receptor α, ERα-negative breast cancers are dissociated from any endocrine regimens in the routine clinical setting, triple-negative breast cancer in particular. However, the stereotype was challenged by triple-negative breast cancers’ retained sensitivity and vulnerability to endocrine agents. The interplay of hormone action and the carcinogenic signaling program previously underscored was gradually recognized along with the increasing investigation. In parallel, the overlooked endocrine-responsiveness in ERα-negative breast cancers attracted attention and supplied fresh insight into the therapeutic strategy in an ERα-independent manner. This review elaborates on the genomic and non-genomic steroid hormone actions and endocrine-related signals in triple-negative breast cancers attached to the hormone insensitivity label. We also shed light on the non-canonical mechanism detected in common hormone agents to showcase their pleiotropic effects.

Objectives: To evaluate the efficacy and safety of first-line treatment with a dendritic cell vaccination for lung cancer (DCVAC/LuCa), standard of care chemotherapy and Shenqi Fuzheng injection in patients with advanced (stage IIIB/IV) non-small cell lung cancer. Patients and Methods: Patients with histologically or cytologically confirmed recurrent metastatic or advanced NSCLC (stage IIIB/IV) with wild-type epidermal growth factor receptor (EGFR) or EGFR mutation which does not confer increased tumor susceptibility to EGFR-interacting drugs were recruited. For the treatment period, the first cycle of standard of care therapy (SoC) started 2 to 14 days after the leukapheresis procedure. SoC continued 4 to 6 cycles. DCVAC/LuCa was administered from the second cycle of SoC. DCVAC/LuCa was administered in a 3-week cycle schedule (5 doses) and then in a 6-week cycle schedule. Shenqi Fuzheng injection was administered 3 days before each DCVAC/LuCa administration for a total of 14 daily doses. Patients would undergo disease evaluation by computed tomography (CT) scan every 3 months. The primary and secondary endpoint was efficacy with regard to objective response rate (ORR) and progression free survival (PFS). The safety profile was measured by: incidence, type, and severity of all adverse events (AEs), laboratory abnormalities (blood routine test, urine test, and chemical test), physical status, and vital signs. Qi insufficiency was evaluated by tongue diagnosis and questionnaire survey with “Classification and Determination of constitution in TCM.” Results: Twenty-three patients from 3 hospitals who received combination therapy were included. ORR was 34.8% (95% CI:16.4%-57.3%). Median duration of response was 5.51 m (95% CI:2.70-8.32). Median PFS was 10.72 m (95% CI:4.52-16.93), 1-year survival was 77.8%. mOS was 21.97 m (95% CI:13.68-30.25). There was 1 severe AE related to a history of heart disease and there were no adverse events related to DCVAC/LuCa treatment. Qi insufficiency was improved significantly ( P

Abstract Background Diarrhea is a common adverse reaction in patients with cancer receiving chemotherapy, for which there is currently no effective method of treatment. Shengjiang Xiexin decoction (SXD), a classic traditional Chinese medicine (TCM) formula, has shown efficacy in alleviating irinotecan-induced diarrhea in preliminary clinical studies. The current study is designed to assess the efficacy and safety of SXD for prophylaxis against irinotecan-induced diarrhea. Additionally, we employ a new approach to analyze and evaluate the data based on the patients’ uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) genotype, which predicts the risk of diarrhea. Methods and design A prospective, double-blind, randomized, placebo-controlled trial will be conducted in patients with small cell lung cancer (SCLC) from five hospitals in China. For this study, 100 irinotecan-naïve patients will be randomly allocated to either the SXD or placebo arms in a 1:1 ratio. Stratified randomization will be used to divide subjects by UGT1A1 genotype into groups with differing risk of diarrhea. The trial will consist of two cycles of chemotherapy with 14 days of oral administration of SXD or placebo administered beginning between 3 days before and up to 11 days after initiation of each chemotherapy cycle. The primary study outcome is the incidence of diarrhea. Secondary outcomes include the degree of diarrhea, the degree of neutropenia, the rate of alterations in chemotherapy regimens, the amount of antidiarrheal drug taken, the rate of hospitalization, and evaluation of chemotherapy efficacy. Discussion This study is the first to use the UGT1A1 genotype to stratify patients into groups based on their risk of diarrhea, and to provide a complete assessment of chemotherapy-related diarrhea (CRD), including records of diarrhea duration, grading the severity of diarrhea, and evaluating concomitant symptoms. Study results will provide high-level clinical evidence on the use of SXD as prophylaxis for CRD. Trial registration Chinese Clinical Trial Register: ChiCTR1800018490. Registered on 20 September 2018. Retrospectively registered. http://www.chictr.org.cn/edit.aspx?pid=25250&htm=4c

As observed with other chemotherapeutic agents, the clinical application of platinum agents is a double-edged sword. Platinum-induced peripheral neuropathy (PIPN) is a common adverse event that negatively affects clinical outcomes and patients’ quality of life. Considering the unavailability of effective established agents for preventing or treating PIPN and the increasing population of cancer survivors, the identification and development of novel, effective interventions are the need of the hour. Plant-derived medicines, recognized as ideal agents, can not only help improve PIPN without affecting chemotherapy efficacy, but may also produce synergy. In this review, we present a brief summary of the mechanisms of platinum agents and PIPN and then focus on exploring the preventive or curative effects and underlying mechanisms of plant-derived medicines, which have been evaluated under platinum-induced neurotoxicity conditions. We identified 11 plant extracts as well as 17 plant secondary metabolites, and four polyherbal preparations. Their effects against PIPN are focused on oxidative stress and mitochondrial dysfunction, glial activation and inflammation response, and ion channel dysfunction. Also, ten clinical trials have assessed the effect of herbal products in patients with PIPN. The understanding of the molecular mechanism is still limited, the quality of clinical trials need to be further improved, and in terms of their efficacy, safety, and cost effectiveness studies have not provided sufficient evidence to establish a standard practice. But plant-derived medicines have been found to be invaluable sources for the development of natural agents with beneficial effects in the prevention and treatment of PIPN.

Background: Hepatocellular carcinoma (HCC) is the most common type of liver cancer and causes many cancer-related deaths worldwide; in China it is the second most prevalent cause of cancer deaths. Most patients are diagnosed clinically with advanced stage disease. Summary: For more than a decade, sorafenib, a small molecular weight tyrosine kinase-inhibitor (SMW TKI) was the only molecular targeted drug available with a survival benefit for the treatment of advanced HCC. With the development of novel TKIs and immune checkpoint inhibitors (ICIs) for advanced HCC, the management of patients has been greatly improved. However, though angiogenic-based targeted therapy remains the backbone for the systemic treatment of HCC, to date no Chinese guidelines for novel molecular targeted therapies to treat advanced HCC have been established. Our interdisciplinary panel on the treatment of advanced HCC comprising hepatologists, hepatobiliary surgeons, oncologists，radiologists，pathologists, orthopedic surgeons, traditional Chinese medicine physicians and interventional radiologists have reviewed the literature in order to develop updated treatment regimens. Key Messages: Panel consensus statements for the appropriate use of new molecular targeted drugs including doses, combination therapies, adverse reaction management as well as efficacy evaluation and predictions for treatment of advanced HCC with evidence levels based on published data are presented, thereby providing an overview of molecular targeted therapies for healthcare professionals.

Based on the enhanced charge separation efficiency of the one-dimensional structure and strong surface plasmon resonance (SPR) of gold, a gold modified TiO2 nanotube (Au/TiO2NTs) glucose photoelectrochemical (PEC) sensor was prepared. It could be activated by visible red light (625 nm). Under optimal conditions, the Au/TiO2NTs sensor exhibited a good sensitivity of 170.37 μA·mM−1·cm−2 in the range of 1–90 μM (R2 = 0.9993), and a detection limit of 1.3 μM (S/N = 3). Due to its high selectivity, good anti-interference ability, and long-term stability, the fabricated Au/TiO2NTs sensor provides practical detection of glucose. It is expected to be used in the construction of non-invasive PEC biosensors.

Background: LC09 is composed with 5 kinds of traditional Chinese herbal medicines ( Astragalus membranaceus , flowers carthami, lithospermum, geranium wilfordii, and radix angelicae) which are used in China and developed over several thousand years. Aim: To assess the effectiveness and safety of herbal compound LC09 on patients with capecitabine-associated hand-foot syndrome (HFS). Materials and Methods: In this randomized, double-blind, and parallel-controlled study, 156 patients that diagnosed with HFS were randomly assigned to a treatment group (n = 78) or control group (n = 78). Patients were evaluated every week by the National Cancer Institute (NCI) grade and Numerical Rating Scale (NRS) pain scores. The Dermatology Life Quality Index (DLQI) scale and Instrumental Activity of Daily Living (IADL) scale were used to assess the quality of life before the treatment, and at 1 week and after the treatment of 2 cycles. Results: At the baseline, no significant differences were observed between the 2 groups. After treatment, significant differences in NCI grade and NRS pain scores were observed between the 2 groups ( P < .01). In addition, HFS effectiveness rate and pain alleviation rate were significantly higher in the treatment group compared with the control group ( P < .01). Furthermore, the chemotherapy completion rate between 2 groups was significantly different ( P = .002). In addition, no adverse reactions were observed in either LC09 or control group. Conclusion: LC09 can decrease NCI grade and significantly alleviate pain in HFS patients. Besides, it can also increase chemotherapy completion rate.

Photocatalytic water splitting for hydrogen generation is a significant pathway for sustainable energy conversion and production. The photocatalysts with a Z-scheme water splitting charge transfer pathway is superior due to the good separation and migration ability of photoexcited charge carriers. Herein, Co3O4/g-C3N4 photocatalysts with Z-scheme charge transfer pathway were successfully constructed by an electrostatic interaction-annealing method. The as-prepared Co3O4/g-C3N4 ultra-thin nanosheets were tested and analyzed by XRD, EA, ICP, SEM, TEM, AFM, XPS, UV-Vis DRS, PL and photoelectrochemical measurements. Moreover, the influences of fabrication parameters on performance of Co3O4/g-C3N4 catalysts were investigated, and 0.5% Co3O4/g-C3N4 exhibited the optimal activity. Based on the characterization and catalytic performance, the Z-scheme charge transfer pathway of Co3O4/g-C3N4 was established and put forward. To further improve the catalytic performance of Co3O4/g-C3N4, 0.5% Pt was added as a co-catalyst. The obtained Pt/0.5% Co3O4/g-C3N4 was recyclable and remained the original catalytic water splitting performance within 20 h. The modification of Co3O4 and Pt improved the separation and migration of e− and h+, and induced the increased hydrogen evolution rate of g-C3N4.

In a genome-wide association study, we identified a rice UDP-glycosyltransferase gene, OsUGT706D2, whose transcription was activated in response to cold and submergence stress and to exogenous abscisic acid (ABA). OsUGT706D2 positively regulated the biosynthesis of tricin-4′-O-(syringyl alcohol) ether-7-O-glucoside at both the transcriptional and metabolic levels. OsUGT706D2 mediated cold and submergence tolerance by modulating the expression of stress-responsive genes as well as the abscisic acid (ABA) signaling pathway. Gain of function of OsUGT706D2 increased cold and submergence tolerance and loss of function of OsUGT706D2 reduced cold tolerance. ABA positively regulated OsUGT706D2-mediated cold tolerance but reduced submergence tolerance. These findings suggest the potential use of OsUGT706D2 for improving abiotic stress tolerance in rice.

Abstract Plant metabolites including anthocyanins play an important role in the growth of plants, as well as in regulating biotic and abiotic stress responses to the environment. Here we report comprehensive profiling of 3315 metabolites and a further metabolic-based genome-wide association study (mGWAS) based on 292,485 SNPs obtained from 311 rice accessions, including 160 wild and 151 cultivars. We identified hundreds of common variants affecting a large number of secondary metabolites with large effects at high throughput. Finally, we identified a novel gene namely OsLSC6 (Oryza sativa leaf sheath color 6), which encoded a UDP 3-O-glucosyltransferase and involved in the anthocyanin biosynthesis of Cyanidin-3-Galc (sd1825) responsible for leaf sheath color, and resulted in significant different accumulation of sd1825 between wild (purple) and cultivars (green). The results of knockout transgenic experiments showed that OsLSC6 regulated the biosynthesis and accumulation of sd1825, controlled the purple leaf sheath. Our further research revealed that OsLSC6 also confers resistance to cold stress during the seedling stage in rice. And we identified that a SNP in OsLSC6 was responsible for the leaf sheath color and chilling tolerance, supporting the importance of OsLSC6 in plant adaption. Our study could not only demonstrate that OsLSC6 is a vital regulator during anthocyanin biosynthesis and abiotic stress responses, but also provide a powerful complementary tool based on metabolites-to-genes analysis by mGWAS for functional gene identification andpromising candidate in future rice breeding and improvement.

Abstract Introduction Previous studies have reported controversial relationships between circulating vascular endothelial growth factors (VEGF) and ischemic stroke (IS). This study aims to demonstrate the causal effect between VEGF and IS using Mendelian randomization (MR). Methods Summary statistics data from two large-scale genome-wide association studies (GWAS) for 16,112 patients with measured VEGF levels and 40,585 patients with IS were downloaded from public databases and included in this study. A published calculator was adopted for MR power calculation. The primary outcome was any ischemic stroke, and the secondary outcomes were large-artery stroke, cardioembolic stroke, and small-vessel stroke. We used the inverse variance-weighted (IVW) method for primary analysis, supplemented by MR-Egger regression and the weighted median method. Results Nine SNPs were included to represent serum VEGF levels. The IVW method revealed no strong causal association between VEGF and any ischemic stroke (odds ratio [OR] 1.01, 95% CI 0.99–1.04, p = 0.39), cardioembolic stroke (OR 1.04, 95% CI 0.97–1.12, p = 0.28), large-artery stroke (OR 1.02, 95% CI 0.95–1.09, p = 0.62), and small-vessel stroke (OR 0.98, 95% CI 0.91–1.04, p = 0.46). These findings remained robust in sensitivity analyses. MR-Egger regression suggested no horizontal pleiotropy. Conclusions This Mendelian randomization study found no relationship between genetically predisposed serum VEGF levels and risks of IS or its subtypes.

Abstract Carbohydrates, proteins, lipids, minerals and vitamins are nutrient substances commonly seen in rice grains, but anthocyanidin, with benefit for plant growth and animal health, exists mainly in the common wild rice but hardly in the cultivated rice. To screen the rice germplasm with high intensity of anthocyanidins and identify the variations, we used metabolomics technique and detected significant different accumulation of anthocyanidins in common wild rice (Oryza rufipogon, with purple leaf sheath) and cultivated rice (Oryza sativa, with green leaf sheath). In this study, we identified and characterized a well-known MYB transcription factor, OsC1, through phenotypic (leaf sheath color) and metabolic (metabolite profiling) genome-wide association studies (pGWAS and mGWAS) in 160 common wild rice (O. rufipogon) and 151 cultivated (O. sativa) rice varieties. Transgenic experiments demonstrated that biosynthesis and accumulation of cyanidin-3-Galc, cyanidin 3-O-rutinoside and cyanidin O-syringic acid, as well as purple pigmentation in leaf sheath were regulated by OsC1. A total of 25 sequence variations of OsC1 constructed 16 functional haplotypes (higher accumulation of the three anthocyanidin types within purple leaf sheath) and 9 non-functional haplotypes (less accumulation of anthocyanidins within green leaf sheath). Three haplotypes of OsC1 were newly identified in our germplasm, which have potential values in functional genomics and molecular breeding of rice. Gene-to-metabolite analysis by mGWAS and pGWAS provides a useful and efficient tool for functional gene identification and omics-based crop genetic improvement.

Background The authors aimed to elucidate the relationship between latest ischemic event and the incidence of subsequent ischemic stroke in patients with symptomatic artery occlusion. Methods and Results We analyzed the association between qualifying event—the latest ischemic event (transient ischemic attack [TIA] or stroke)—and the incidence of ipsilateral ischemic stroke in patients with symptomatic artery occlusion treated with medical therapy alone in CMOSS (Carotid or Middle Cerebral Artery Occlusion Surgery Study). The incidence of CMOSS primary outcomes, including any stroke or death within 30 days after randomization or ipsilateral ischemic stroke between 30 days and 2 years, between the bypass surgical and medical groups, stratified by qualifying events, was also compared. Of the 165 patients treated with medical therapy alone, 75 had a TIA and 90 had a stroke as their qualifying event. The incidence of ipsilateral ischemic stroke did not significantly differ between patients with a TIA and those with a stroke as their qualifying event (13.3% versus 6.7%, P=0.17). In multivariate analysis, the qualifying event was not associated with the incidence of ipsilateral ischemic stroke. There were no significant differences in the CMOSS primary outcomes between the surgical and medical groups, regardless of the qualifying event being TIA (10.1% versus 12.2%, P=0.86) or stroke (6.7% versus 8.9%, P=0.55). Conclusions Among patients with symptomatic artery occlusion and hemodynamic insufficiency, the risk of subsequent ipsilateral ischemic stroke does not appear to be lower in patients presenting with a TIA compared with those with a stroke. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01758614.

Background: There is a lack of comprehensive profile assessment on complete blood count (CBC)-derived systemic-inflammatory indices, and their correlations with clinical outcome in patients with anterior circulation acute ischemic stroke (AIS) who achieved successful recanalization by endovascular thrombectomy (EVT). Methods: Patients with anterior circulation AIS caused by large vessel occlusion (AIS-LVO) were retrospectively screened from December 2018 to December 2022. Systemic-inflammatory indices including ratios of neutrophil-to-lymphocyte (NLR), monocyte-to-lymphocyte (MLR), platelet-to-lymphocyte (PLR), and platelet-to-neutrophil (PNR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and aggregate inflammation systemic index (AISI) on admission and the first day post-EVT were calculated. Their correlations with symptomatic intracranial hemorrhage (sICH) and unfavorable 90-day functional outcome (modified Rankin Scale score of 3–6) were analyzed. Results: A total of 482 patients [65 (IQR, 56–72) years; 33 % female] were enrolled, of which 231 (47.9 %) had unfavorable 90-day outcome and 50 (10.4 %) developed sICH. Day 1 neutrophil and monocyte counts, NLR, MLR, PLR, SII, SIRI, and AISI were increased, while lymphocyte and PNR were decreased compared to their admission levels. In multivariate analyses, neutrophil count, NLR, SII, and AISI on day 1 were independently associated with 90-day functional outcome. Moreover, day 1 neutrophil count, NLR, MLR, PLR, PNR, SII, and SIRI were independently linked to the occurrence of sICH. No admission variables were identified as independent risk factors for patient outcomes. Conclusion: CBC-derived systemic-inflammatory indices measured on the first day after successful EVT are predictive of 90-day functional outcome and the sICH occurrence in patients with anterior circulation AIS-LVO.

Abstract Background With the increasing frequency of climatic anomalies, high temperatures and long-term rain often occur during the rice-harvesting period, especially for early rice crops in tropical and subtropical regions. Seed dormancy directly affects the resistance to pre-harvest sprouting (PHS). Therefore, in order to increase rice production, it is critical to enhance seed dormancy and avoid yield losses to PHS. The elucidation and utilization of the seed dormancy regulation mechanism is of great significance to rice production. Preliminary results indicated that the OsMKKK62-OsMKK3-OsMPK7/14 module might regulate ABA sensitivity and then control seed dormancy. The detailed mechanism is still unclear. Results The overexpression of OsMKK3 resulted in serious PHS. The expression levels of OsMKK3 and OsMPK7 were upregulated by ABA and GA at germination stage. OsMKK3 and OsMPK7 are both located in the nucleus and cytoplasm. The dormancy level of double knockout mutant mkk3/mft2 was lower than that of mkk3, indicating that OsMFT2 functions in the downstream of MKK3 cascade in regulating rice seeds germination. Biochemical results showed that OsMPK7 interacted with multiple core ABA signaling components according to yeast two-hybrid screening and luciferase complementation experiments, suggesting that MKK3 cascade regulates ABA signaling by modulating the core ABA signaling components. Moreover, the ABA response and ABA responsive genes of mpk7/14 were significantly higher than those of wild-type ZH11 when subjected to ABA treatment. Conclusion MKK3 cascade mediates the negative feedback loop of ABA signal through the interaction between OsMPK7 and core ABA signaling components in rice.

ABSTRACTThe root-associated microbiota has a close relation to the life activities of plants, and its composition is affected by the rhizospheric environment and plant genotypes. Rice (Oryza sativa) was domesticated from the ancestor species Oryza rufipogon. Many important agricultural traits and adversity resistance of rice have changed during a long time of natural domestication and artificial selection. However, the influence of rice genotypes on root microbiota in important agricultural traits remains to be explained. In this study, we performed 16S rRNA and internal transcribed spacer (ITS) gene amplicon sequencing to generate bacterial and fungal community profiles of O. rufipogon and O. sativa, both of which were planted in a farm in Guangzhou and had reached the reproductive stage. We compared their root microbiota in detail by alpha diversity, beta diversity, different species, core microbiota, and correlation analyses. We found that the relative abundance of bacteria was significantly higher in the cultivated rice than in the common wild rice, while the relative abundance of fungi was the opposite. Significant differences in agricultural traits between O. rufipogon and O. sativa showed a high correlation with core microorganisms in the two Oryza species, which only existed in either or had obviously different abundance in both two species, indicating that rice genotype/phenotype had a strong influence on recruiting specific microorganisms. Our study provides a theoretical basis for the in-depth understanding of rice root microbiota and the improvement of rice breeding from the perspective of the interaction between root microorganisms and plants.IMPORTANCEPlant root microorganisms play a vital role not only in plant growth and development but also in responding the biotic and abiotic stresses. Oryza sativa is domesticated from Oryza rufipogon which has many excellent agricultural traits especially containing resistance to biotic and abiotic stresses. To improve the yield and resistance of cultivated rice, it is particularly important to deeply research on differences between O. sativa and O. rufipogon and find beneficial microorganisms to remodel the root microbiome of O. sativa.

Background: Carotid arterial atherosclerotic stenosis is a well-recognized pathological basis of ischemic stroke; however, its underlying molecular mechanisms remain unknown. Vascular smooth muscle cells (VSMCs) play fundamental roles in the initiation and progression of atherosclerosis. Organelle dynamics have been reported to affect atherosclerosis development. However, the association between organelle dynamics and various cellular stresses in atherosclerotic progression remain ambiguous. Methods: In this study, we conducted transcriptomics and bioinformatics analyses of stable and vulnerable carotid plaques. Primary VSMCs were isolated from carotid plaques and subjected to histopathological staining to determine their expression profiles. Endoplasmic reticulum (ER), mitochondria, and lysosome dynamics were observed in primary VSMCs and VSMC cell lines using live-cell imaging. Moreover, the mechanisms underlying disordered organelle dynamics were investigated using comprehensive biological approaches. Results: ER whorls, a representative structural change under ER stress, are prominent dynamic reconstructions of VSMCs between vulnerable and stable plaques, followed by fragmented mitochondria and enlarged lysosomes, suggesting mitochondrial stress and lysosomal defects, respectively. Induction of mitochondrial stress alleviated ER stress and autophagy in an eukaryotic translation initiation factor (eIF)-2α-dependent manner. Furthermore, the effects of eIF2α on ER stress, mitochondrial stress, and lysosomal defects were validated using clinical samples. Conclusion: Our results indicate that morphological and functional changes in VSMC organelles, especially in ER whorls, can be used as reliable biomarkers for atherosclerotic progression. Moreover, eIF2α plays an important role in integrating multiple stress-signaling pathways to determine the behavior and fate of VSMCs.

Background This study aimed to investigate regional levels of TAT (thrombin‐antithrombin complex), PIC (plasmin‐α2 plasmin inhibitor complex), t‐PAIC (tissue plasminogen activator‐plasminogen activator inhibitor complex), sTM (soluble thrombomodulin), and D‐dimer, along with their associations with clinical and procedural characteristics in patients with acute ischemic stroke undergoing endovascular thrombectomy. Methods and Results We retrospectively analyzed 166 consecutive patients with acute ischemic stroke (62±11.54 years of age, 34.3% women) using prospectively maintained clinical databases and blood samples from local ischemic (proximal to thrombus) and systemic (femoral artery, self‐control) arterial compartments. Levels of TAT, PIC, t‐PAIC, and D‐dimer were significantly elevated, whereas sTM was significantly reduced, in local ischemic regions compared with their systemic levels. Each 1‐unit increase in ischemic TAT (adjusted odds ratio [aOR], 1.086 [95% CI, 1.03–1.145]; P=0.002; area under the curve [AUC], 0.833) and PIC (aOR, 1.337 [95% CI, 1.087–1.644]; P=0.006; AUC, 0.771) correlated significantly with higher symptomatic intracranial hemorrhage risk. Additionally, each 1‐unit increase in ischemic TAT (aOR, 1.076 [95% CI, 1.016–1.139]; P=0.013; AUC, 0.797), PIC (aOR, 1.554 [95% CI, 1.194–2.022]; P=0.001; AUC, 0.798), and sTM (aOR, 0.769 [95% CI, 0.615–0.961]; P=0.021; AUC, 0.756) was significantly associated with an increased risk of an unfavorable 90‐day outcome (modified Rankin scale of 3–6). These hemostatic molecules, individually or combined, significantly improved the predictive power of conventional risk factors, as evidenced by significant increases in net reclassification improvement and integrated discrimination improvement (all P

Abstract Background Stroke is a heavy burden in modern society, and carotid artery disease is a major cause. The role of the extracellular matrix (ECM) in the development and progression of carotid artery disease has become a popular research focus. However, there is no published bibliometric analysis to derive the main publication features and trends in this scientific area. We aim to conduct a bibliometric analysis to reveal current status of ECM in carotid artery disease and to predict future hot spots. Methods We searched and downloaded articles from the Web of Science Core Collection with “Carotid” and “Extracellular Matrix” as subject words from 1990 to 2021. The complete bibliographic data were analyzed by Bibliometrics, BICOMB, gCLUTO and CiteSpace softwares. Results Since 1990, the United States has been the leader in the number of publications in the field of ECM in carotid artery disease, followed by China, Japan and Germany. Among institutions, Institut National De La Sante Et De La Recherche Medicale Inserm, University of Washington Seattle and Harvard University are in the top 3. “Arteriosclerosis Thrombosis and Vascular Biology” is the most popular journal and “Circulation” is the most cited journal. “Clowes AW”, “Hedin Ulf” and “Nilsson Jan” are the top three authors of published articles. Finally, we investigated the frontiers through the strongest citation bursts, conducted keyword biclustering analysis, and discovered five clusters of research hotspots. Our research provided a comprehensive analysis of the fundamental data, knowledge organization, and dynamic evolution of research about ECM in carotid artery disease. Conclusions The field of ECM in carotid artery disease has received increasing attention. We summarized the history of the field and predicted five future hotspots through bibliometric analysis. This study provided a reference for researchers in this fields, and the methodology can be extended to other fields.

The rate by which the different regions in China have caught up with the national growth in the current reform period, which have varied from time to time, is highly dependent on the available human and government resources. China, to its credit, has pledged to continue the reform programs and work to harmonize its economic system. The central government acknowledges the need to empower the interior regions to help them achieve economic development.

Bacterial leaf blight (BLB), among the most serious diseases in rice production, is caused by Xanthomonas oryzae pv. oryzae (Xoo). Xa23, the broadest resistance gene against BLB in rice, is widely used in rice breeding. In this study, the rice variety CBB23 carrying the Xa23 resistance gene was inoculated with AH28 and PXO99A to identify differentially expressed genes (DEGs) associated with the resistance. Transcriptome sequencing of the infected leaves showed 7997 DEGs between the two strains at different time points, most of which were up-regulated, including cloned rice anti-blight, peroxidase, pathology-related, protein kinase, glucosidase, and other coding genes, as well as genes related to lignin synthesis, salicylic acid, jasmonic acid, and secondary metabolites. Additionally, the DEGs included 40 cloned, five NBS-LRR, nine SWEET family, and seven phenylalanine aminolyase genes, and 431 transcription factors were differentially expressed, the majority of which belonged to the WRKY, NAC, AP2/ERF, bHLH, and MYB families. Metabolomics analysis showed that a large amount of alkaloid and terpenoid metabolite content decreased significantly after inoculation with AH28 compared with inoculation with PXO99A, while the content of amino acids and their derivatives significantly increased. This study is helpful in further discovering the pathogenic mechanism of AH28 and PXO99A in CBB23 rice and provides a theoretical basis for cloning and molecular mechanism research related to BLB resistance in rice.

Background: The aim of this study was to exploit integrated PET/MRI to simultaneously evaluate the morphological, component, and metabolic features of advanced atherosclerotic plaques and explore their incremental value. Methods: In this observational prospective cohort study, patients with advanced plaque in the carotid artery underwent 18F-FDG PET/MRI. Plaque morphological features were measured, and plaque component features were determined via MRI according to AHA lesion-types. Maximum standardized uptake values (SUVmax) and tissue to background ratio (TBR) on PET were calculated. Area under the receiver-operating characteristic curve (AUC) and net reclassification improvement (NRI) were used to compare the incremental contribution of FDG uptake when added to AHA lesion-types for symptomatic plaque classification. Results: A total of 280 patients with advanced plaque in the carotid artery were recruited. A total of 402 plaques were confirmed, and 87 of 402 (21.6%) were symptomatic plaques. 18F-FDG PET/MRI was performed a mean of 38 days (range 1–90) after the symptom. Increased stenosis degree (61.5% vs. 50.0%, p < 0.001) and TBR (2.96 vs. 2.32, p < 0.001) were observed in symptomatic plaques compared with asymptomatic plaques. The performance of the combined model (AHA lesion type VI + stenosis degree + TBR) for predicting symptomatic plaques was the best among all models (AUC = 0.789). The improvement of the combined model (AHA lesion type VII + stenosis degree + TBR) over AHA lesion type VII model for predicting symptomatic plaques was the highest (AUC = 0.757/0.454, combined model/AHA lesion type VII model), and the NRI was 50.7%. Conclusions: Integrated PET/MRI could simultaneously evaluate the morphological component and inflammation features of advanced atherosclerotic plaques and provide supplementary optimization information over AHA lesion-types for identifying vulnerable plaques in atherosclerosis subjects to achieve further stratification of stroke risk.

Summary: Low hierarchy and disruptive functionality of carbonaceous materials from biomass pyrolysis restrict their energy and environmental applications. Here, we report a cascade strategy to engineer bagasse into activated porous carbon with regulated morphology and functional groups. The initial pyrolysis of bagasse at 350°C –850°C facilitates curve sheet morphology and random meso-/micro-porosity. The subsequent alkali calcination leads to a micropore and comb-like structure with specific surface area and pore volume of 1,276.7 m2/g and 579.5 × 10−3 cm3/g, respectively. The last acid rinse removes the remaining –OH and –COO groups on the biochar surface. As a result, activated porous carbon processed at 450°C and activated with KOH/HCl exhibits the highest adsorption capacity of 103.4 mg/g at a rapid equilibrium rate fitted with Freundlich adsorption isotherm and facilitates steady mercury removal under pH 3–11. This study provides an effective approach to engineering agricultural waste into superior adsorbents for wastewater remediation. Science for society: Mercury contamination is a significant public health and environmental problem. Cost-effective and high-performance remediation methods have gained attention in both academic and industrial fields. Agricultural waste is an attractive resource as it provides rich carbon components with a modifiable structure to manufacture commercial adsorbents, namely, activated carbon. We present an approach that overcomes the existing issues in the complex structure and composition of activated carbon from waste heating. Highly orderly and regulated biochar fabricated from bagasse—sugarcane pulp—can be used for effective mercury adsorption under different conditions. This approach may facilitate the remediation of mercury-containing wastewater in a sustainable manner.