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Zaoqin Yu,1,&ast; Wei Li,1,&ast; Xiaofang Shangguan,2 Yuanxuan Cai,2 Qianyan Gao,1 Ximin Wang,1 Yuan Chen,3 Dong Liu,1 Chengliang Zhang1 1Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 2School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 3Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dong Liu; Chengliang ZhangDepartment of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of ChinaTel/Fax +86-27-83663643; +86-27-83663519Email ld2069@outlook.com; clzhang@tjh.tjmu.edu.cnBackground: Despite the great signs of progress in cancer pain management in China, the associated pain remains under-treated. Poor knowledge among the medical staff is an important factor contributing to the under-treatment of cancer pain. This study aimed to evaluate the knowledge, practices, and perceived barriers in cancer pain management among the medical staff at oncology units in China.Patients and Methods: A cross-sectional survey was conducted with the medical staff (including physicians, nurses, and pharmacists) at oncology units in tertiary hospitals of China between December 2020 and January 2021. The questionnaire assessed the knowledge, practices, and perceived barriers in cancer pain management.Results: A total of 1262 medical staff responded to the questionnaire; the response rate was 94.2%. Most participants had good knowledge of the three-step analgesic ladder of the World Health Organization (WHO) and the National Comprehensive Cancer Network (NCCN) guidelines for Adult Cancer Pain. Knowledge deficit was prominent in questions on opioid dose titration and rotation and adverse effects of opioids; the correct response rate was less than 40%. Training, work experience in oncology, and education level were significantly related to knowledge of cancer pain management (all P < 0.001). In clinical practice for cancer pain management, approximately 57.2% of medical staff were unfamiliar with opioid dose titration and rotation; only 14.4% treated cancer pain through multidisciplinary collaboration. Poor medication compliance, difficult individualized analgesia protocols, and insufficient multidisciplinary participation were the most frequently perceived barriers by the medical staff for pain management.Conclusion: These findings suggested a further need for integrating recent guidelines to strengthen continued training (especially among juniors and those with low education levels) and patient education to improve the knowledge and clinical practices of cancer pain management among the medical staff in China. Multi-disciplinary management is required for the effective treatment of cancer pain.Keywords: cancer pain, medical staff, knowledge, practices, barriers, multi-disciplinary management

Embryo size is a critical trait determining not only grain yield but also the nutrition of the maize kernel. Up to present, only a few genes have been characterized affecting the maize embryo/kernel ratio. Here, we identify 63 genes significantly associated with maize embryo/kernel weight ratio using a genome-wide association study (GWAS). The peak GWAS signal shows that the natural variation in Zea mays COMPACT PLANT2 (CT2), encoding the heterotrimeric G protein α subunit, is significantly associated with the Embryo/Kernel Weight Ratio (EKWR), Further analyses show that a missense mutation of CT2 decreases its enzyme activity and associates with EKWR. The function of CT2 on affecting embryo/kernel weight ratio is further validated by characterization of two ct2 mutants, for which EKWR is significantly decreased. Subsequently, the key downstream genes of CT2 are identified by combining the differential expression analysis (DEG) of the ct2 mutant and quantitative trait transcript analysis in the GWAS population. In addition, the allele frequency spectrum shows that CT2 was under selective pressure during maize domestication. This study provides important genetic insights into the natural variation of maize embryo/kernel weight ratio, which could be applied in future maize breeding programs to improve grain yield and nutritional content., Competing Interests: Declaration of Competing Interest All authors declare that there are no conflicts of interest., (Copyright © 2024. Published by Elsevier Ltd.)

This study explores the prognostic value of immune escape-related genes in acute myeloid leukemia (AML) patients. Using TARGET&#95;AML and GSE37642 datasets, we identified CEP55, DNAJC13, and EMC2 as significant prognostic indicators, with high transcript abundance correlating with poor outcomes. Consensus clustering divided patients into two groups, with Cluster 1 showing worse prognosis. A prognostic signature based on these genes stratified patients into high- and low-risk groups, with the high-risk group experiencing worse outcomes. The risk score was an independent prognostic factor. Functional analysis revealed that high-risk genes could promote cell cycle progression. The selected genes were strongly associated with immune cells, particularly mast cells and CD8+ T cells. This study enriches the prognostic evaluation system for AML and suggests a new therapeutic direction.

Although copper (Cu) is an essential microelement for plant growth and development, excess Cu results in a dramatic reduction in crop yield and quality. In the present study, we report that rice germin-like protein 8-7 (OsGLP8-7) plays a crucial role against Cu toxicity. The results showed that the transcriptional expression of the OsGLP8-7 gene was remarkably upregulated in the root and leaf by Cu treatment. The depletion of OsGLP8-7 significantly decreased the elongation of the primary root and plant height of rice under excess Cu. This hypersensitivity of osglp8-7 mutants towards excess Cu may be attributed to the weaker Cu retention in the cell wall compared with wild-type rice (Dongjin, DJ). Consistently, Cu-induced phenylpropanoid biosynthesis was compromised in osglp8-7 mutants based on RNA-Seq and qRT-PCR analysis. Furthermore, osglp8-7 mutants displayed a reduction of lignin deposition in the cell wall, and subsequently altered cell morphology. Osglp8-7 mutant lines also had higher Cu-induced O 2 • - and H 2 O 2 levels than those of DJ under Cu stress. The results suggest that OsGLP8-7 participates in lignin synthesis for the acclimation to excess Cu. These findings provide a better understanding of a novel mechanism of germin-like proteins in the alleviation of heavy metal toxicity in rice., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Eltrombopag combined with immunosuppressive therapy (IST) was superior to IST alone for severe aplastic anemia (SAA) in the previous studies. But in China, horse antithymocyte globulin (hATG) is not available, instead, we use rabbit ATG (rATG). Here, we compared the efficacy and safety of IST (rATG combined with cyclosporine) combined with or without eltrombopag for the first-line treatment of SAA and very severe aplastic anemia (VSAA). A total of 371 patients in ten institutions in China from April 1, 2017 to December 1, 2022 were enrolled. The overall response (OR) rate at 3 months (54.2% vs. 41%; P = 0.046), the complete response (CR) (31.3% vs. 19.4%; P = 0.041) and OR (78.3% vs. 51.1%; P < 0.0001) rates at 6 months were significantly higher with IST combined with eltrombopag than with IST alone in SAA patients. While in VSAA patients, the addition of eltrombopag to IST only increased the CR rate at 6 months (29.8% vs. 9.43%; P = 0.010). Liver injury increased significantly in groups treated with IST combined with eltrombopag (P < 0.05). Serious treatment-related toxicities were similar (P > 0.05). In patients with SAA, 3-year failure-free survival (FFS) of eltrombopag combined with IST group was significantly higher than that of IST group (70.7 ± 5.3% vs. 50.3 ± 3.9%; P = 0.007). In patients with VSAA, the addition of eltrombopag significantly improved 3-year overall survival (OS) (82.2 ± 5.7% vs. 57.3 ± 7.2%; P = 0.020). Our findings suggested that IST combined with eltrombopag could improve the hematological recovery of newly diagnosed SAA without increasing severe toxicities. But in VSAA, the addition of eltrombopag seemed to show no other improvement to efficacy except the CR rate at 6 months., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In this study, the whole HD-Zip family members of G. hirsutum were identified, and GhHDZ76 was classified into the HD-Zip IV subgroup. GhHDZ76 was predominantly expressed in the 0-5 DPA of fiber development stage and localized in the nucleus. Overexpression of GhHDZ76 significantly increased the length and density of trichomes in Arabidopsis thaliana. The fiber length of GhHDZ76 knockout lines by CRISPR/Cas9 was significantly shorter than WT at the early elongation and mature stage, indicating that GhHDZ76 positively regulate the fiber elongation. Scanning electron microscopy showed that the number of ovule surface protrusion of 0 DPA of GhHDZ76 knockout lines was significantly lower than WT, suggesting that GhHDZ76 can also promote the initiation of fiber development. The transcript level of GhWRKY16, GhRDL1, GhEXPA1 and GhMYB25 genes related to fiber initiation and elongation in GhHDZ76 knockout lines were significantly decreased. Yeast two-hybrid and Luciferase complementation imaging (LCI) assays showed that GhHDZ76 can interact with GhWRKY16 directly. As a transcription factor, GhHDZ76 has transcriptional activation activity, which could bind to L1-box elements of the promoters of GhRDL1 and GhEXPA1. Double luciferase reporter assay showed that the GhWRKY16 could enhance the transcriptional activity of GhHDZ76 to pGhRDL1, but it did not promote the transcriptional activity of GhHDZ76 to pGhEXPA1. GhHDZ76 protein may also promote the transcriptional activity of GhWRKY16 to the downstream target gene GhMYB25. Our results provided a new gene resource for fiber development and a theoretical basis for the genetic improvement of cotton fiber quality., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Sugar transporters play important roles in controlling carbohydrate transport and are responsible for mediating the movement of sugars into cells in numerous organisms. In insects, sugar transporters not only play a role in sugar transport but may also act as receptors for virus entry and the accumulation of plant defense compounds. The brown planthopper, Nilaparvata lugens , inflicts damage on rice plants by feeding on their phloem sap, which is rich in sugars. In the present study, we identified 34 sugar transporters in N. lugens , which were classified into three subfamilies based on phylogenetic analysis. The motif numbers varied from seven to eleven, and motifs 2, 3, and 4 were identified in the functional domains of all 34 NlST proteins. Chromosome 1 was found to possess the highest number of NlST genes, harboring 15. The gut, salivary glands, fat body, and ovary were the different tissues enriched with NlST gene expression. The expression levels of NlST2 , 3 , 4 , 7 , 20 , 27 , 28 , and 31 were higher in the gut than in the other tissues. When expressed in a Saccharomyces cerevisiae hexose transporter deletion mutant (strain EBY.VW4000), only ApST4 (previously characterized) and NlST4, 28, and 31 were found to transport glucose and fructose, resulting in functional rescue of the yeast mutant. These results provide valuable data for further studies on sugar transporters in N. lugens and lay a foundation for finding potential targets to control N. lugens .

Purpose: To evaluate whether BeEAM is an alternative to BEAM for autologous stem cell transplantation (ASCT) in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL)., Methods: Data of 60 patients with relapsed or refractory DLBCL who underwent ASCT from January 2018 to June 2023 in our center, including 30 patients in the BeEAM group and 30 patients in the BEAM group, were retrospectively analyzed. The time to hematopoietic reconstitution, treatment-related adverse events, number of hospitalization days, hospitalization cost, and survival benefit were compared between the two groups., Results: The clinical characteristics of the patients did not significantly differ between the two groups. The median number of reinfused CD34 + cells was 5.06 × 10 6 /kg and 5.17 × 10 6 /kg in the BeEAM and BEAM groups, respectively, which did not significantly different (p = 0.8829). In the BeEAM and BEAM groups, the median time to neutrophil implantation was 10.2 and 10.27 days, respectively (p = 0.8253), and the median time to platelet implantation was 13.23 and 12.87 days, respectively (p = 0.7671). In the BeEAM and BEAM groups, the median hospitalization duration was 30.37 and 30.57 days, respectively (p = 0.9060), and the median hospitalization cost was RMB 83,425 and RMB 96,235, respectively (p = 0.0560). The hospitalization cost was lower in the BeEAM group. The most common hematologic adverse events were grade ≥ 3 neutropenia and thrombocytopenia, whose incidences were similar in the two groups. The most common non-hematologic adverse events were ≤ grade 2 and the incidences of these events did not significantly differ between the two groups. Median overall survival was not reached in either group, with predicted 5-year overall survival of 72.5% and 60% in the BeEAM and BEAM groups, respectively (p = 0.5872). Five-year progression-free survival was 25% and 20% in the BeEAM and BEAM groups, respectively (p = 0.6804)., Conclusion: As a conditioning regimen for relapsed or refractory DLBCL, BeEAM has a desirable safety profile and is well tolerated, and its hematopoietic reconstitution time, number of hospitalization days, and survival benefit are not inferior to those of BEAM. BeEAM has a lower hospitalization cost and is an alternative to BEAM., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The predominant characteristic of autoimmune gastritis (AIG) is corpus-dominant advanced atrophy, which is mostly observed in the middle to late stages. More reports are needed on the endoscopic features of the early stage. In this report, we present two cases of early-stage AIG in which endoscopic examinations showed no atrophy of the gastric mucosa but displayed a transition of collecting venules from a regular to an irregular arrangement. In addition, yellowish-white cobblestone-like elevations were observed in the fundic gland region. Histologically, the observed manifestations included pseudohypertrophy and protrusion of parietal cells into the lumen, possibly along with hyperplasia of G cells, lymphocytic infiltration and potentially pseudopyloric gland metaplasia. Serologically, the anti-parietal cell antibody returned positive results, whereas the anti-intrinsic factor antibody yielded negative results. In this study, we summarized some endoscopic features of two patients, aiming to provide clues for endoscopists to detect early-stage AIG., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yu, Shangguan, Yu, Wu, Xu and Tan.)

Lignin is a phenolic biopolymer generated from phenylpropanoid pathway in the secondary cell wall and is required for defense of plants against various stress. Although the fact of stress-induced lignin deposition has been clearly demonstrated, it remains largely elusive how the formation of lignin is promoted under Cu stress. The present study showed that OsGLP8-7, an extracellular glycoprotein of rice (Oryza sativa L.), plays an important function against Cu stress. The loss function of OsGLP8-7 results in Cu sensitivity whereas overexpression of OsGLP8-7 scavenges Cu-induced superoxide anion (O 2 • -). OsGLP8-7 interacts with apoplastic peroxidase111 (OsPRX111) and elevates OsPRX111 stability when exposed to excess Cu. In OsGLP8-7 overexpressing (OE) lines, the retention of Cu within cell wall limiting Cu uptake into cytoplasm is attributed to the enhanced lignification required for Cu tolerance. Exogenous application of a lignin inhibitor can impair the Cu tolerance of transgenic Arabidopsis lines overexpressing OsGLP8-7. In addition, co-expression of OsGLP8-7 and OsPRX111 genes in tobacco leaves leads to an improved lignin deposition compared to leaves expressing each gene individually or the empty vector. Taken together, our findings provided the convincing evidences that the interaction between OsGLP8-7 and OsPRX111 facilitates effectively lignin polymerization, thereby contributing to Cu tolerance in rice., Competing Interests: Declaration of competing interest The authors declare that they have no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Objective: To explore the construction and application in the practice of green channel in No. 971 Naval Hospital of PLA (No. 971 Hospital mode) for the treatment of acute ischemic stroke (AIS)., Methods: This retrospective study involved a cohort of 694 suspected stroke patients from December 2022 to November 2023 undergoing emergency treatment for stroke at our institution. Among them, 483 patients were treated with standard green channel (the control group), and 211 patients adopted the No. 971 Hospital mode for treatment (the study group). The biggest difference between the two groups was that the treatment process started before admission. We compared the effectiveness of the emergency treatment between the two groups and the thrombolysis treatment., Results: Compared with control group, the accuracy rate of determining stroke and the rate of thrombolysis were significantly higher ( p = 0.002, 0.039) and the door to doctor arrival time (DAT) and the door to CT scan time (DCT) of the study group was significantly shorter (all p < 0.001). There were 49 patients (10.1%) and 33 patients (15.6%) from the control group and study group receiving thrombolysis, respectively. The DAT, DCT, imaging to needle time (INT), and door to needle time (DNT) of patients receiving thrombolysis in the study group were significantly shorter than that in the control group (all p < 0.01). The NIHSS in the study group after the thrombolysis was lower than that in the control group ( p = 0.042)., Conclusion: No. 971 Hospital model can effectively shorten DAT, DCT, INT, and DNT, and improve the effectiveness of thrombolysis and prognoses of AIS patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yan, Du, Shangguan, Li, Chi, Wang, Cheng, Huang, Pan and Xin.)

The use of an appropriate preparation route is the key to immobilize active molecules into a host matrix with high loadings and stability. Herein, we demonstrate a simple and general strategy to immobilize ferrocene and its derivatives into ZIF-8 with high loadings of up to 4.3% Fe content. The unique host pore structure allows for the stabilization of guest molecules and effectively prevents their leaching. As a result, the obtained electrocatalysts exhibit competitive oxygen evolution reaction (OER) catalytic performance. Optimized Fc-CHO/ZIF-8 requires only a low overpotential of 238 mV to achieve 10 mA cm -2 , along with a relatively small Tafel slope of 44.4 mV dec -1 . This performance is superior to that of commercial IrO 2 , suggesting its potential application in electrochemical energy conversion.

Objective: The influence of vitamin D on autoimmune thyroid disease (AITD) remains a subject of ongoing debate. This study employs Mendelian randomization (MR) to investigate the causal correlations of serum 25-hydroxyvitamin D (25[OH]D) levels with autoimmune thyroiditis (AIT), autoimmune hyperthyroidism (AIH), and Graves disease (GD)., Methods: Data on single nucleotide polymorphisms related to serum 25(OH)D levels, AIT, AIH, and GD were sourced from UK Biobank and FinnGen. Inverse variance weighted, MR-Egger, and weighted median were employed to test the exposure-outcome causal relationship. Assessments of horizontal pleiotropy, heterogeneity, and stability were performed using the MR-Egger intercept, Cochran's Q test, and leave-one-out sensitivity analysis, respectively., Results: The results of MR analysis showed increased serum 25(OH)D levels was associated with a reduced risk of AIT (OR 0.499, 95% CI 0.289 to 0.860, p = 0.012) but not causal associated with AIH (OR 0.935, 95% CI 0.695 to 1.256, p = 0.654) and GD (OR 0.813, 95% CI 0.635 to 1.040, p = 0.100). Intercept analysis showed no horizontal pleiotropy ( p > 0.05), and Cochran's Q test showed no heterogeneity ( p > 0.05). Sensitivity analysis suggested that these results were robust., Conclusion: An increased serum 25(OH)D level is associated with AIT risk reduction but unrelated to AIH and GD. This finding suggests that vitamin D supplementation can be valuable for preventing and treating AIT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yu, Yang, Wu, Shangguan, Bai and Yu.)

Background and Aims: Identifying potential high-risk groups of oxaliplatin-induced liver injury (OILI) is valuable, but tools are lacking. So artificial neural network (ANN) and logistic regression (LR) models will be developed to predict the risk of OILI., Methods: The medical information of patients treated with oxaliplatin between May and November 2016 at 10 hospitals was collected prospectively. We used the updated Roussel Uclaf causality assessment method (RUCAM) to identify cases of OILI and summarized the patient and medication characteristics. Furthermore, the ANN and LR models for predicting the risk of OILI were developed and evaluated., Results: The incidence of OILI was 3.65%. The median RUCAM score with interquartile range was 6 (4, 9). The ANN model performed similarly to the LR model in sensitivity, specificity, and accuracy. In discrimination, the area under the curve of the ANN model was larger (0.920>0.833, p =0.019). In calibration, the ANN model was slightly improved. The important predictors of both models overlapped partially, including age, chemotherapy regimens and cycles, single and total dose of OXA, glucocorticoid drugs, and antihistamine drugs., Conclusions: When the discriminative and calibration ability was given priority, the ANN model outperformed the LR model in predicting the risk of OILI. Other chemotherapy drugs in oxaliplatin-based chemotherapy regimens could have different degrees of impact on OILI. We suspected that OILI may be idiosyncratic, and chemotherapy dose factors may be weakly correlated. Decision making on prophylactic medications needs to be carefully considered, and the actual preventive effect needed to be supported by more evidence., Competing Interests: The authors have no conflict of interests related to this publication., (© 2023 Authors.)

Silicon nitride is a bioceramic with great potential, and multiple studies have demonstrated its biocompatibility and antibacterial properties. In this study, silicon nitride was prepared by a microwave sintering technique that was different from common production methods. SEM and pore distribution analysis revealed the microstructure of microwave-sintered silicon nitride with obvious pores. Mechanical performance analysis shows that microwave sintering can improve the mechanical properties of silicon nitride. The CCK-8 method was used to demonstrate that microwave-sintered silicon nitride has no cytotoxicity and good cytocompatibility. From SEM and CLSM observations, it was observed that there was good adhesion and cross-linking of cells during microwave-sintered silicon nitride, and the morphology of the cytoskeleton was good. Microwave-sintered silicon nitride has been proven to be non-cytotoxic. In addition, the antibacterial ability of microwave-sintered silicon nitride against Staphylococcus aureus and Escherichia coli was tested, proving that it has a good antibacterial ability similar to the silicon nitride prepared by commonly used processes. Compared with silicon nitride prepared by gas pressure sintering technology, microwave-sintered silicon nitride has excellent performance in mechanical properties, cell compatibility, and antibacterial properties. This indicates its enormous potential as a substitute material for manufacturing bone implants.

The Bph15 gene, known for its ability to confer resistance to the brown planthopper (BPH; Nilaparvata lugens Stål), has been extensively employed in rice breeding. However, the molecular mechanism by which Bph15 provides resistance against BPH in rice remains poorly understood. In this study, we reported that the transcription factor OsWRKY71 was highly responsive to BPH infestation and exhibited early-induced expression in Bph15 -NIL (near-isogenic line) plants, and OsWRKY71 was localized in the nucleus of rice protoplasts. The knockout of OsWRKY71 in the Bph15 -NIL background by CRISPR-Cas9 technology resulted in an impaired Bph15 -mediated resistance against BPH. Transcriptome analysis revealed that the transcript profiles responsive to BPH differed between the wrky71 mutant and Bph15 -NIL, and the knockout of OsWRKY71 altered the expression of defense genes. Subsequent quantitative RT-PCR analysis identified three genes, namely sesquiterpene synthase OsSTPS2 , EXO70 family gene OsEXO70J1 , and disease resistance gene RGA2 , which might participate in BPH resistance conferred by OsWRKY71 in Bph15 -NIL plants. Our investigation demonstrated the pivotal involvement of OsWRKY71 in Bph15 -mediated resistance and provided new insights into the rice defense mechanisms against BPH., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Zhang, Shangguan, Yin, Zhu, Hu, Du and Lv.)

Carbapenem-resistant Enterobacterales (CRE) constitute an urgent threat to worldwide public health. The spread of CRE is facilitated by transmission via the environment. Wastewater treatment plants (WWTPs) are considered to be important sources of antibiotic resistance and hot spots of antibiotic-resistant bacteria (ARB) which can facilitate dissemination of antibiotic resistance genes. In this study, water samples were collected over one year from a WWTP in Jinan, Shandong province, China, from different functional sites in the wastewater treatment process. Carbapenem-resistant Escherichia coli (CREC) were isolated by selective cultivation and whole-genome sequenced to investigate the occurrence and characteristics of CREC in the WWTP. A total of 77 CREC isolates were included in the study and the detection rate of CREC in the WWTP water inlet was found to be 85%. An additional 10 CREC were isolated from a nearby teaching hospital during the sampling period and included for comparison to the environmental isolates. Susceptibility testing showed that all CREC were multidrug-resistant. 6 different carbapenem resistance genes (CRGs) were detected, including bla NDM-5 (n = 75), bla NDM-1 (n = 6), bla NDM-4 (n = 3), bla NDM-6 (n = 1), bla NDM-9 (n = 1), and bla KPC-2 (n = 4). 42 CREC isolates were whole-genome sequenced with Illumina short-read sequencing. 11 of these were also sequenced with Nanopore long-read sequencing. Plasmids carrying CRGs were found to belong to IncX3 (n = 35), IncFII (n = 12), IncFIA (n = 5), IncFIB (n = 2), IncC (n = 1), and IncP6 (n = 1). Clonal dissemination of CREC belonging to ST167, ST448, and ST746 was observed between different parts of the WWTP. Furthermore, isolates from the WWTP, including an isolate belonging to the high-risk ST167 strain, were found to be clonally related to CREC isolated at the hospital. The spread of CRGs is of considerable concern and strategies to prevent environmental dissemination of this contaminant urgently needs to be implemented., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The maintain of iron (Fe) homeostasis is essential for plant survival. In tomato, few transcription factors have been identified as regulators of Fe homeostasis, among which SlbHLH068 induced by iron deficiency, plays an important role. However, the upstream regulator(s) responsible for activating the expression of SlbHLH068 remain(s) unknown. In this study, the bHLH (basic helix-loop-helix) transcription factor SlbHLH152 was identified as an upstream regulator of SlbHLH068 using yeast one-hybrid screening. Deletion of SlbHLH152 led to a significant decline in Fe concentration, which was accompanied by reduced expression of Fe-deficiency-responsive genes. In contrast, SlbHLH152 overexpression plants displayed tolerance to iron deficiency, increased Fe accumulation, and elevated expression of Fe-deficiency-responsive genes. Further analysis indicated that SlbHLH152 directly activates the transcription of SlbHLH068. Taken together, our results suggest that SlbHLH152 may be involved in the regulation of iron homeostasis by directly activating the transcription of SlbHLH068 in tomato., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Preoperative diagnosis of the cause of adhesive small bowel obstruction (ASBO) is very challenging for surgeons. We aimed to develop a nomogram model for the identification of banded adhesions (BA) and matted adhesions (MA) of ASBO., Methods: This retrospective study enrolled patients with ASBO between January 2012 and December 2020, classified into BA and MA groups according to the intraoperative findings. A nomogram model was developed by using multivariable logistic regression analysis., Results: A total of 199 patients were included, with 117 (58.8%) cases of BA and 82 (41.2%) cases of MA. There were 150 patients designed for training the model, and the other 49 cases for validation. Multivariate logistic regression analysis showed that prior surgery for once (p = 0.008), white blood cells (WBC) (p = 0.001), beak sign (p < 0.001), fat notch sign (p = 0.013), and mesenteric haziness (p = 0.005) were independently associated with BA. The AREA under the receiver operating characteristic curve (AUC-ROC) of the nomogram model in the training and validation sets were 0.861 (95% CI 0.802-0.921) and 0.884 (95% CI 0.789-0.980), respectively. The calibration plot demonstrated a good agreement. A decision curve analysis demonstrated that the nomogram model was clinically useful., Conclusions: The multi-analysis of the nomogram model might have a favorable clinical applicability for the identification of BA and MA in patients with adhesive small bowel obstruction., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Plants deploy receptor-like kinases and nucleotide-binding leucine-rich repeat receptors to confer host plant resistance (HPR) to herbivores 1 . These gene-for-gene interactions between insects and their hosts have been proposed for more than 50 years 2 . However, the molecular and cellular mechanisms that underlie HPR have been elusive, as the identity and sensing mechanisms of insect avirulence effectors have remained unknown. Here we identify an insect salivary protein perceived by a plant immune receptor. The BPH14-interacting salivary protein (BISP) from the brown planthopper (Nilaparvata lugens Stål) is secreted into rice (Oryza sativa) during feeding. In susceptible plants, BISP targets O. satvia RLCK185 (OsRLCK185; hereafter Os is used to denote O. satvia-related proteins or genes) to suppress basal defences. In resistant plants, the nucleotide-binding leucine-rich repeat receptor BPH14 directly binds BISP to activate HPR. Constitutive activation of Bph14-mediated immunity is detrimental to plant growth and productivity. The fine-tuning of Bph14-mediated HPR is achieved through direct binding of BISP and BPH14 to the selective autophagy cargo receptor OsNBR1, which delivers BISP to OsATG8 for degradation. Autophagy therefore controls BISP levels. In Bph14 plants, autophagy restores cellular homeostasis by downregulating HPR when feeding by brown planthoppers ceases. We identify an insect saliva protein sensed by a plant immune receptor and discover a three-way interaction system that offers opportunities for developing high-yield, insect-resistant crops., (© 2023. The Author(s).)

C-Mos , a proto-oncogene, regulates oocyte maturation by activating the classical MAPK pathway in cells. To examine the function of C-Mos in Hyriopsis cumingii , C-Mos was identified in this study. The full-length cDNA of C-Mos was 2213 bp, including 144 bp in the 5' UTR, 923 bp in 3' the UTR, and 1146 bp in the open reading frame (ORF) region. During early gonad development, the expression of C-Mos from 4 to 6 months of age in H. cumingii was significantly higher than that in other months, with the highest expression in 6-month-old H. cumingii , suggesting that C-Mos may be involved in early gonadal development in H. cumingii . Clear hybridization signals were found by in situ hybridization in the oocytes, oocyte nucleus and oogonium, and a small number of hybridization signals were found in the follicular wall of the male gonads. In addition, the C-Mos RNA interference (RNAi) assay results showed that the knockdown of C-Mos caused a down-regulation of ERK and P90rsk . In summary, these results indicate that C-Mos has a crucial part to play in gonadal development in H. cumingii .

Despite unequivocal roles in disease, transcription factors (TFs) remain largely untapped as pharmacologic targets due to the challenges in targeting protein-protein and protein-DNA interactions. Here we report a chemical strategy to generate modular synthetic transcriptional repressors (STRs) derived from the bHLH domain of MAX. Our synthetic approach yields chemically stabilized tertiary domain mimetics that cooperatively bind the MYC/MAX consensus E-box motif with nanomolar affinity, exhibit specificity that is equivalent to or beyond that of full-length TFs and directly compete with MYC/MAX protein for DNA binding. A lead STR directly inhibits MYC binding in cells, downregulates MYC-dependent expression programs at the proteome level and inhibits MYC-dependent cell proliferation. Co-crystallization and structure determination of a STR:E-box DNA complex confirms retention of DNA recognition in a near identical manner as full-length bHLH TFs. We additionally demonstrate structure-blind design of STRs derived from alternative bHLH-TFs, confirming that STRs can be used to develop highly specific mimetics of TFs targeting other gene regulatory elements., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Copper (Cu) and cadmium (Cd) are common heavy metal pollutants. When Cd and excessive Cu accumulate in plants, plant growth is reduced. Our previous study showed that Germin-like proteins (GLPs), which exist in tandem on chromosomes, are a class of soluble glycoproteins that respond to Cu stress. In this study, hydroponic cultures were carried out to investigate the effect of GLP on Cd and Cu tolerance and accumulation in rice. The results showed that knockout of a single OsGLP8 - 2 gene or ten OsGLP genes ( OsGLP8 - 2 to OsGLP8 - 11 ) resulted in a similar sensitivity to Cd and Cu toxicity. When subjected to Cu and Cd stress, the glp8 - 2 and glp8 - (2 - 11) mutants displayed a more sensitive phenotype based on the plant height, root length, and dry biomass of the rice seedlings. Correspondingly, Cu and Cd concentrations in the glp8 - 2 and glp8 - (2 - 11) mutants were significantly higher than those in the wild-type (WT) and OsGLP8 - 2 -overexpressing line. However, Cu and Cd accumulation in the cell wall was the opposite. Furthermore, we determined lignin accumulation. The overexpressing- OsGLP8 - 2 line had a higher lignin accumulation in the shoot and root cell walls than those of the WT, glp8 - 2 , and glp8 - (2 - 11) . The expression of lignin synthesis genes in the OsGLP8 - 2 -overexpressing line was significantly higher than that in the WT, glp8 - 2 , and glp8 - (2 - 11) . The SOD activity of OsGLP8 - 2 , Diaminobe-nzidine (DAB), propidium iodide (PI) staining, and Malondialdehyde (MDA) content determination suggested that OsGLP8 - 2 is involved in heavy metal-induced antioxidant defense in rice. Our findings clearly suggest that OsGLPs participate in responses to heavy metal stress by lignin deposition and antioxidant defense capacity in rice, and OsGLP8-2 may play a major role in the tandem repeat gene clusters of chromosome 8 under heavy metal stress conditions., Competing Interests: Author AW was employed by the company CNTC. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 ShangGuan, Qi, Wang, Ren, Wang, Xiao, Shen, Wang and Xia.)

Objectives: Distracted driving such as reading phone messages during driving is risky, as it increases the probability of severe crashes. This study proposes an XGBoost model for visual distraction detection based on vehicle dynamics data from a driving simulation study., Methods: A simulated driving experiment involving thirty-six drivers was launched. We obtained the vehicle dynamics parameters required for the model using the time window and fast Fourier transform methods, totaling 26 items. Meanwhile, the effects of varied time window sizes (1-7 s) and amount of input indications on model performance were studied., Results: By conducting a comparative analysis, it has been determined that the ideal time window size is 5 s. Additionally, the optimal number of input indicators was found to be 23. The XGBoost model for distinguishing distractions achieved an accuracy rate of 85.68%, a precision rate of 85.83%, a recall rate of 83.85%, an F1 score of 84.82%, and an AUC value of 0.9319, which were higher than SVM and RF. The gain-based feature rank demonstrated that the standard deviation of vehicle sideslip rate and the mean amplitude of the 0-1 Hz spectrum component of the steering wheel angle were more crucial than other features., Conclusions: The research results indicate that the steering wheel angle and vehicle sideslip angle may be more conducive to identifying distractions. This XGBoost model could potentially be applied in advanced driving assistant systems (ADAS) to warn driver and reduce cellphone involved distracted driving.

The Ti600/TC18 dissimilar titanium alloy joints were prepared by inertia friction welding (IFW). Then, stress-relief annealing and two-stage annealing were performed to optimize the microstructure and properties of the original joints, the purpose of them is to improve the structure and performance of the joints. Then, the microstructure, phase composition, tensile properties, microhardness, and fracture morphology of the joints after heat treatments were investigated. The results showed that after stress-relief annealing, the microstructure of the joints was almost similar to that of the specimen before annealing; the weld zone (WZ) of the joints was composed of fine recrystallized grains and α', and the more β phases underwent a martensitic transformation. The shapes and sizes of α p phases were increased after two-stage annealing; its percentage content was decreased. The tensile properties and the microhardness values of the joints undergoing stress-relief annealing were relatively higher than that of the joints undergoing two-stage annealing; there was no obvious change in the plasticity of the joints. It was confirmed that the stress-relief annealing microstructure was composed of α' and β phases, which were beneficial to the properties of the joints. However, the α s phases were coarsened after two-stage annealing, and the properties of the joints were reduced.

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&#95;A07G0817/GH&#95;D07G0819) and GhMETTL3 (GH&#95;A12G2586/GH&#95;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., Competing Interests: The authors declare no conflict of interest.

Studying economic development in China is a very important topic recently because China's economy is moving toward high-quality development and local governments face the dilemma of environmental governance and economic development. To contribute to the literature in this area further, this paper assesses the impact of tax competition and environmental regulation on high-quality economic development through the spatial Durbin model and instrumental variable and by using the data from 278 prefecture-level and above cities from 2007 to 2017 in China. Our empirical analysis shows that tax competition inhibits high-quality economic development and a positive spatial spillover effect, environmental regulation has a significant direct promoting effect on high-quality economic development and a negative spatial spillover effect, and local government tax competition inhibits the promotion effect of environmental regulation on high-quality economic development. Further heterogeneity analysis conducted in our study shows that both the direct and spatial spillover effects of tax competition and environmental regulation on high-quality economic development in large and medium-sized cities are significantly lower than those in small cities. Our empirical analysis infers that since the 18th National Congress of the Communist Party of China, the promotion effect of environmental regulation on high-quality economic development and the synergistic effect with tax competition has become more and more significant. The findings in our paper are useful for both the central government and the local governments in making better decisions for economic development in China as well as in other countries., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shangguan, Hashmi, Hu and Wong.)

An unprecedented copper-catalyzed four-component reaction of arylcyclopropanes, nitriles, carboxylic acids and N -fluorobenzenesulfonimide (NFSI) has been successfully developed, which represents the first example of a four-component reaction of non-donor-acceptor cyclopropanes. A wide range of imide derivatives were efficiently synthesized in excellent yields under mild conditions., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Objectives: The patients' attitude is critical in disease control. This study aims to explore the determinants of patients' attitude and satisfaction., Methods: A total of 844 patients in the rural areas of Shandong, Henan, and Sichuan provinces with hypertension or diabetes were randomly selected for investigation. The outcome variables were the patients' attitude and satisfaction toward chronic disease control, which were measured through patient self-reported. Binary logistic regression models were used to explore the determinants of patients' attitude and satisfaction., Results: Teachers were more likely to regard that chronic disease management was helpful in their chronic disease control than that in farmers (OR = 3.994, 95% confidence interval (CI) = 1.309-12.188). Moreover, the probability of health institutions recording chronic diseases changes and guiding rehabilitation for patients regularly is considered helpful 2.688 times more than those that are not. In addition, receiving chronic disease management services can make patients repute that chronic disease management services are helpful in controlling chronic diseases more capably (OR = 1.582, 95% CI = 2.198-10.771). In terms of satisfaction, patients who do not know regular follow-up tend to be dissatisfied with chronic diseases control result (OR = 0.376, 95% CI = 0.192-0.737; OR = 0.592, 95%CI = 0.417-0.841)., Conclusion: The government increases the promotion of chronic disease management in rural areas to improve patients' awareness. Health institutions also can provide diversified services to meet the needs of more people. At last, paying more attention to the timeliness of health services need to be considered to develop a health plan., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer XG declared a shared affiliation with author(s) YL, YZ, XS, and RH to the handling editor at the time of the review., (Copyright © 2022 Lu, Zhao, Shangguan, Lv and Huang.)

Metacognition plays an important role in young children's learning and daily life activities. Based on Anji Play, we designed a metacognition enhancement program named Circling Curriculum for Metacognition Training (CCMT). With a quasi-experimental design, we examined the effects of the CCMT program on the metacognition of 5-6 year old Chinese children. Two classes of 5-6 year old children were randomly assigned into an experimental group (n = 25, 10 girls, mean age = 65.92 months, SD = 3.58) and a control group (n = 22, 10 girls, mean age = 66.77, SD = 3.87). The experimental group received the three-month CCMT, while the control group received routine teaching activities without imposing any interventions. All children took the metacognition test before and after the intervention. Results indicated that (1) there was no significant difference between the experimental group and the control group in all dimensions of metacognitive ability in the pre-test; (2) the experimental group exhibited better metacognitive ability than the control group in most dimensions of metacognitive ability in the post-test; and (3) the gain scores in the metacognitive ability of experimental group were significantly higher than those of the control group. The results are very encouraging and suggest that CCMT can foster the development of the metacognitive ability of young children.

Background: Existing studies have indicated that gut microbiota is closely related to the occurrence and development of coronary heart disease(CHD). Gut microbiota and its metabolites may be important diagnostic markers for CHD in the future and are expected to become new targets for the prevention and treatment of CHD. However, the current studies exploring the link between CHD and gut microbiota are miscellaneous and poorly targeted, without bibliometric analysis available., Objective: The purpose of this research was to perform a bibliometric and visual analysis of published papers on the relationship between CHD and gut microbiota. The study also sought to identify principal authors, institutions, and countries to analyze the research status and trends of gut microbiota research in the field of CHD., Methods: The Web of Science Core Collection (WoSCC) database was searched for publications on CHD and gut microbiota between 2002 and 2022. CiteSpace 5.8. R1, VOSviewer 1.6.16, and Microsoft Excel 2019 software tools were utilized to perform this bibliometric analysis and visualization., Results: There were 457 qualified publications found in total, with the annual number of publications increasing. The United States dominated in this field. Hazen, Stanley l was the author of the most papers. Cleveland Clinic published the most papers of any institution. The six main clusters' specific characteristics were discovered through analysis of the co-occurrence of keywords: inflammation, diet, trimethylamine n-oxide, metabolism, cardiovascular disease, and myocardial infarction. Newly emerging research has focused predominantly on gut microbiota metabolites and recent strategies for intervention in coronary atherosclerosis., Conclusion: These results provided a useful perspective on current research and future prospects for the research on the link between CHD and gut microbiota, which may help researchers to select suitable collaborators and facilitate their research to elucidate the underlying molecular mechanisms of CHD, including the causes, prevention, and treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Long, Mao, Zhang, Liu, Shangguan, Zou, Zhu and Wang.)