The soybean sugar transporter GmSWEET6 participates in sucrose transport towards fungi during arbuscular mycorrhizal symbiosis.

In arbuscular mycorrhizal (AM) symbiosis, sugars in root cortical cells could be exported as glucose or sucrose into peri-arbuscular space for use by AM fungi. However, no sugar transporter has been identified to be involved in sucrose export. An AM-inducible SWEET transporter, GmSWEET6, was functionally characterised in soybean, and its role in AM symbiosis was investigated via transgenic plants. The expression of GmSWEET6 was enhanced by inoculation with the cooperative fungal strain in both leaves and roots. Heterologous expression in a yeast mutant showed that GmSWEET6 mainly transported sucrose. Transgenic plants overexpressing GmSWEET6 increased sucrose concentration in root exudates. Overexpression or knockdown of GmSWEET6 decreased plant dry weight, P content, and sugar concentrations in non-mycorrhizal plants, which were partly recovered in mycorrhizal plants. Intriguingly, overexpression of GmSWEET6 increased root P content and decreased the percentage of degraded arbuscules, while knockdown of GmSWEET6 increased root sugar concentrations in RNAi2 plants and the percentage of degraded arbuscules in RNAi1 plants compared with wild-type plants when inoculated with AM fungi. These results in combination with subcellular localisation of GmSWEET6 to peri-arbuscular membranes strongly suggest that GmSWEET6 is required for AM symbiosis by mediating sucrose efflux towards fungi.

Protein kinase C epsilon promotes de novo lipogenesis and tumor growth in prostate cancer cells by regulating the phosphorylation and nuclear translocation of pyruvate kinase isoform M2.

Protein kinase C epsilon (PKCε) belongs to a family of serine/threonine kinases that control cell proliferation, differentiation and survival. Aberrant PKCε activation and overexpression is a frequent feature of numerous cancers. However, its role in regulation of lipid metabolism in cancer cells remains elusive. Here we report a novel function of PKCε in regulating of prostate cancer cell proliferation by modulation of PKM2-mediated de novo lipogenesis. We show that PKCε promotes de novo lipogenesis and tumor cell proliferation via upregulation of lipogenic enzymes and lipid contents in prostate cancer cells. Mechanistically, PKCε interacts with NABD (1-388) domain of C-terminal deletion on pyruvate kinase isoform M2 (PKM2) and enhances the Tyr105 phosphorylation of PKM2, leading to its nuclear localization. Moreover, forced expression of mutant Tyr105 (Y105F) or PKM2 inhibition suppressed de novo lipogenesis and cell proliferation induced by overexpression of PKCε in prostate cancer cells. In a murine tumor model, inhibitor of PKM2 antagonizes lipogenic enzymes expression and prostate cancer growth induced by overexpression of PKCε in vivo. These data indicate that PKCε is a critical regulator of de novo lipogenesis, which may represent a potential therapeutic target for the treatment of prostate cancer.

CyanoOmicsDB: an integrated omics database for functional genomic analysis of cyanobacteria.

With their photosynthetic ability and established genetic modification systems, cyanobacteria are essential for fundamental and biotechnological research. Till now, hundreds of cyanobacterial genomes have been sequenced, and transcriptomic analysis has been frequently applied in the functional genomics of cyanobacteria. However, the massive omics data have not been extensively mined and integrated. Here, we describe CyanoOmicsDB (http://www.cyanoomics.cn/), a database aiming to provide comprehensive functional information for each cyanobacterial gene. CyanoOmicsDB consists of 8 335 261 entries of cyanobacterial genes from 928 genomes. It provides multiple gene identifiers, visualized genomic location, and DNA sequences for each gene entry. For protein-encoding genes, CyanoOmicsDB can provide predicted gene function, amino acid sequences, homologs, protein-domain super-families, and accession numbers for various public protein function databases. CyanoOmicsDB integrates both transcriptional and translational profiles of Synechocystis sp. PCC 6803 under various environmental culture coditions and genetic backgrounds. Moreover, CyanoOmicsDB includes 23 689 gene transcriptional start sites, 94 644 identified peptides, and 16 778 post-translation modification sites obtained from transcriptomes or proteomes of several model cyanobacteria. Compared with other existing cyanobacterial databases, CyanoOmicsDB comprises more datasets and more comprehensive functional information. CyanoOmicsDB will provide researchers in this field with a convenient way to retrieve functional information on cyanobacterial genes.

Inhibition of phosphoglycerate dehydrogenase induces ferroptosis and overcomes enzalutamide resistance in castration-resistant prostate cancer cells.

Phosphoglycerate dehydrogenase (PHGDH), the rate-limiting enzyme in the first step of the serine synthesis pathway (SSP), is overexpressed in multiple types of cancers. The androgen receptor inhibitor enzalutamide (Enza) is the primary therapeutic drug for patients with castration-resistant prostate cancer (CRPC). However, most patients eventually develop resistance to Enza. The association of SSP with Enza resistance remains unclear. In this study, we found that high expression of PHGDH was associated with Enza resistance in CRPC cells. Moreover, increased expression of PHGDH led to ferroptosis resistance by maintaining redox homeostasis in Enza-resistant CRPC cells. Knockdown of PHGDH caused significant GSH reduction, induced lipid peroxides (LipROS) increase and significant cell death, resulting in inhibiting growth of Enza-resistant CRPC cells and sensitizing Enza-resistant CRPC cells to enzalutamide treatment both in vitro and in vivo. We also found that overexpression of PHGDH promoted cell growth and Enza resistance in CRPC cells. Furthermore, pharmacological inhibition of PHGDH by NCT-503 effectively inhibited cell growth, induced ferroptosis, and overcame enzalutamide resistance in Enza-resistant CRPC cells both in vitro and in vivo. Mechanically, NCT-503 triggered ferroptosis by decreasing GSH/GSSG levels and increasing LipROS production as well as suppressing SLC7A11 expression through activation of the p53 signaling pathway. Moreover, stimulating ferroptosis by ferroptosis inducers (FINs) or NCT-503 synergistically sensitized Enza-resistant CRPC cells to enzalutamide. The synergistic effects of NCT-503 and enzalutamide were verified in a xenograft nude mouse model. NCT-503 in combination with enzalutamide effectively restricted the growth of Enza-resistant CRPC xenografts in vivo. Overall, our study highlights the essential roles of increased PHGDH in mediating enzalutamide resistance in CRPC. Therefore, the combination of ferroptosis inducer and targeted inhibition of PHGDH could be a potential therapeutic strategy for overcoming enzalutamide resistance in CRPC.

Meta-analysis of peripheral blood eosinophils in clinical testing of chronic obstructive pulmonary disease patients.

Introduction: Meta-analysis was used to investigate the relationship between peripheral blood eosinophil (EOS) levels, clinical characteristics, and prognosis in chronic obstructive pulmonary disease (COPD)patients in previous literature. Aim: To analyse the correlation between peripheral blood EOS levels and clinical characteristics and prognosis of patients with COPD using meta-analysis. Material and methods: In databases such as PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wan Fang Data, literature related to the clinical characteristics or prognosis of COPD patients with high-level EOS published before July 2023 was searched for meta-analysis. Results: Through computer search and screening, 29 articles were ultimately included. The meta-analysis results showed that compared to conventional EOS levels, COPD patients with high EOS levels had a lower proportion of GOLD III-IV grade patients (OR = 00.78, 95% CI (0.68, 0.88), p < 0.001), lower CAT scores (OR = -1.01, 95% CI (-1.75, -0.28), p = 0.007), shorter hospital stay (OR = -1.33, 95% CI (-1.52, -1.14), p < 0.001), and lower mortality rate (OR = 0.53, 95% CI (0.42, 0.66), p < 0.001). The readmission rate was low (OR = 0.40, 95% CI (0.33, 0.48), p < 0.001), and there was no statistically significant difference in FEV1%pred (OR = -0.55, 95% CI (-1.33, 0.23), p = 0.17), higher FEV1/FVC values (OR = -0.45, 95% CI (-1.08, 0.18), p = 0.160), and mechanical ventilation usage rate (OR = 0.89, 95% CI (0.65, 1.21), p = 0.450) among COPD patients with different EOS levels. Conclusions: The levels of peripheral blood EOS in COPD patients are related to lung function, respiratory symptoms, etc.; Moreover, COPD patients with high-level EOS have shorter hospital stays, lower mortality and readmission rates. Therefore, ESO can be used as an auxiliary indicator for clinical symptom diagnosis of COPD patients and as an auxiliary indicator for predicting prognosis.

Evidence Supporting That C-to-U RNA Editing Is the Major Force That Drives SARS-CoV-2 Evolution.

Mutations of DNA organisms are introduced by replication errors. However, SARS-CoV-2, as an RNA virus, is additionally subjected to rampant RNA editing by hosts. Both resources contributed to SARS-CoV-2 mutation and evolution, but the relative prevalence of the two origins is unknown. We performed comparative genomic analyses at intra-species (world-wide SARS-CoV-2 strains) and inter-species (SARS-CoV-2 and RaTG13 divergence) levels. We made prior predictions of the proportion of each mutation type (nucleotide substitution) under different scenarios and compared the observed versus the expected. C-to-T alteration, representing C-to-U editing, is far more abundant that all other mutation types. Derived allele frequency (DAF) as well as novel mutation rate of C-to-T are the highest in SARS-CoV-2 population, and C-T substitution dominates the divergence sites between SARS-CoV-2 and RaTG13. This is compelling evidence suggesting that C-to-U RNA editing is the major source of SARS-CoV-2 mutation. While replication errors serve as a baseline of novel mutation rate, the C-to-U editing has elevated the mutation rate for orders of magnitudes and accelerates the evolution of the virus.

The continuing discovery on the evidence for RNA editing in SARS-CoV-2.

Recent studies have presented strong evidence that C-to-U RNA editing is the driving force that fuels severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolution. The findings finally ended the long-term debate on the evolutionary driving force behind SARS-CoV-2 evolution. Here, we would first acknowledge the breakthroughs made by the recent works, such as using the global SARS-CoV-2 data to demonstrate the major mutation source of this virus. Meanwhile, we would raise a few concerns on the accuracy of their interpretation on C-to-U RNA editing. By re-analysing the SARS-CoV-2 population data, we found that the editing frequency on C-to-U sites did not perfectly correlate with the binding motif of the editing enzyme APOBEC, suggesting that there might be false-positive sites among the C-to-U mutations or the original data did not fully represent the novel mutation rate. We hope our work could help people understand the molecular basis underlying SARS-CoV-2 mutation and also be useful to guide future studies on SARS-CoV-2 evolution.

Targeting proteasomal deubiquitinases USP14 and UCHL5 with b-AP15 reduces 5-fluorouracil resistance in colorectal cancer cells.

5-Fluorouracil (5-FU) is the first-line treatment for colorectal cancer (CRC) patients, but the development of acquired resistance to 5-FU remains a big challenge. Deubiquitinases play a key role in the protein degradation pathway, which is involved in cancer development and chemotherapy resistance. In this study, we investigated the effects of targeted inhibition of the proteasomal deubiquitinases USP14 and UCHL5 on the development of CRC and resistance to 5-FU. By analyzing GEO datasets, we found that the mRNA expression levels of USP14 and UCHL5 in CRC tissues were significantly increased, and negatively correlated with the survival of CRC patients. Knockdown of both USP14 and UCHL5 led to increased 5-FU sensitivity in 5-FU-resistant CRC cell lines (RKO-R and HCT-15R), whereas overexpression of USP14 and UCHL5 in 5-FU-sensitive CRC cells decreased 5-FU sensitivity. B-AP15, a specific inhibitor of USP14 and UCHL5, (1-5 µM) dose-dependently inhibited the viability of RKO, RKO-R, HCT-15, and HCT-15R cells. Furthermore, treatment with b-AP15 reduced the malignant phenotype of CRC cells including cell proliferation and migration, and induced cell death in both 5-FU-sensitive and 5-FU-resistant CRC cells by impairing proteasome function and increasing reactive oxygen species (ROS) production. In addition, b-AP15 inhibited the activation of NF-κB pathway, suppressing cell proliferation. In 5-FU-sensitive and 5-FU-resistant CRC xenografts nude mice, administration of b-AP15 (8 mg·kg-1·d-1, intraperitoneal injection) effectively suppressed the growth of both types of tumors. These results demonstrate that USP14 and UCHL5 play an important role in the development of CRC and resistance to 5-FU. Targeting USP14 and UCHL5 with b-AP15 may represent a promising therapeutic strategy for the treatment of CRC.

Evaluating the effects of Esmolol on cardiac function in patients with Septic cardiomyopathy by Speck-tracking echocardiography-a randomized controlled trial.

BACKGROUND: Esmolol as one treatment of sepsis induced cardiomyopathy (SIC) is still controversial. The objective of this study is to evaluate cardiac function after reducing heart rate by Esmolol in patients with SIC using speck-tracking echocardiography. METHODS: This study was a single-center, prospective, and randomized controlled study. A total of 100 SIC patients with a heart rate more than 100/min, admitted to the Intensive Care Department of Tianjin Third Central Hospital from March 1, 2020 to September 30, 2021, were selected as the research subjects. They were randomly divided into the Esmolol group (Group E) and the conventional treatment group (Group C), each with 50 cases. The target heart rate of patients in Group E was controlled between 80/min and 100/min. Speck-tracking echocardiography (STE) and pulse indicating continuous cardiac output monitoring (PICCO) were performed in both groups at 1 h, 24 h, 48 h, 72 h, 96 h and 7 d after admission, with data concerning left ventricular global longitudinal strain (GLS), left ventricular ejection fraction (LVEF) and global ejection fraction (GEF), left ventricular systolic force index (dP/dtmx) were obtained, respectively. Hemodynamics and other safety indicators were monitored throughout the whole process. These subjects were followed up to 90 d, with their mortality recorded at Day 28 and Day 90, respectively. Statistical analyses were performed using SPSS version 21. RESULTS: With 24 h of Esmolol, all patients in Group E achieved the target heart rate, and there was no deterioration of GLS, or adverse events. However, compared with those in Group C, their GLS, GEF and dP/dtmx were increased, and the difference was statistically significant (P > 0.05). Compared with patients in Group C, those in Group E had lower short-term mortality, and logistic regression analysis also suggested that Esmolol improved patient outcomes. CONCLUSION: In SIC patients, the application of Esmolol to lower heart rate decreased their short-term mortality while not making any impairment on the myocardial contractility. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2100047513. Registered June 20, 2021- Retrospectively registered, http://www.chictr.org.cn/index.aspx . The study protocol followed the CONSORT guidelines. The study protocol was performed in the relevant guidelines.

RTKN2 Inhibits the Growth, Migration, Invasion and Glycolysis of Lung Adenocarcinoma Cells by Inactivating the NF-κB Signalling Pathway.

BACKGROUND: Lung adenocarcinoma (LUAD) is a malignant tumour that seriously threatens the life and health of people worldwide. This research was carried out to investigate the role of Rhotekin 2 (RTKN2) in LUAD progression. METHODS AND RESULTS: The GEPIA online database was used to analyse abnormally expressed genes in lung adenocarcinoma and RTKN2 expression in various cancers. Cell proliferation was detected with CCK-8 and colony formation assays. Transwell assays were carried out to assess cell migration and invasion. The extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) were evaluated by a Seahorse XFe96 analyser. The interaction between RTKN2 and p65 was confirmed using a coimmunoprecipitation assay. RTKN2 expression was detected with qPCR, immunohistochemistry, and western blot assays. The p65 levels in the cytoplasm and nucleus were determined by western blot assays. RTKN2 levels were prominently decreased in LUAD tissues and cell lines. RTKN2 overexpression suppressed LUAD cell growth, invasion, migration, and glycolysis, while RTKN2 knockdown showed the opposite effects. Additionally, p65 could be negatively regulated by RTKN2. RTKN2 overexpression increased p65 levels in the cytoplasm but decreased p65 levels in the nucleus. Furthermore, blocking the NF-κB signalling pathway neutralized the effect of RTKN2 silencing in LUAD cells. CONCLUSION: RTKN2 inhibited the malignant behaviour and glycolysis of LUAD cells by blocking the NF-κB signalling pathway, implying that RTKN2 could be a cancer suppressor in LUAD progression.

Development of a Diagnostic Nomogram to Predict CAP in Hospitalized Patients with AECOPD.

The purpose of this study was to establish a nomogram for predicting community-acquired pneumonia (CAP) in hospitalized patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD). The retrospective cohort study included 1249 hospitalized patients with AECOPD between January 2012 and December 2019. The patients were divided into pneumonia-complicating AECOPD (pAECOPD) and non-pneumonic AECOPD (npAECOPD) groups. The least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression were utilized to identify prognostic factors. A prognostic nomogram model was established, and the bootstrap method was used for internal validation. Discrimination and calibration of the nomogram model were evaluated by receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA). Logistic and LASSO regression analysis showed that C-reactive protein (CRP) >10 mg/L, albumin (Alb) <40 g/L, alanine transferase (ALT) >50 U/L, fever, bronchiectasis, asthma, previous hospitalization for pAECOPD in the past year (Pre-H for pAECOPD), and age-adjusted Charlson score (aCCI) ≥6 were independent predictors of pAECOPD. The area under the ROC curve (AUC) of the nomogram model was 0.712 (95% CI: 0.682-0.741). The corrected AUC of internal validation was 0.700. The model had well-fitted calibration curves and good clinical usability DCA curve. A nomogram model was developed to assist clinicians in predicting the risk of pAECOPD.China Clinical Trials Registry: ChiCTR2000039959.

Analysis of the characteristics of major pollutants discharged from wastewater in China's provinces.

In recent years, the discharge of major pollutants in China's wastewater has been decreasing but remains at a high level. Controlling the discharge of pollutants in sewage is of great importance for protecting water quality and maintaining ecological balance. Based on data collected from 31 provinces in China from 2011 to 2020 (except 2018), this study analyzes the spatiotemporal variation emissions of the wastewater pollutants: chemical oxygen demand (COD), ammonia nitrogen (NH3-N), total nitrogen (TN), and total phosphorus (TP). The entropy method was used to evaluate the effectiveness of water pollution control in different provinces. Our results revealed that the total emission per gross domestic product (GDP) for COD, NH3-N, TN and TP in China decreased by 50.7%, 81.9%, 65.4% and 70.8%, respectively. In terms of regional annual emission differences, the Northwest region was the lowest compared with other regions, accounting for 4.87%-6.59% of the national pollutant emissions, and the Central China region was the highest, accounting for 22.4%-26.05% of the national pollutant emissions. The average value of pollutant emissions per unit of GDP decreased year-to-year overall, but Guangxi and Tibet showed a trend of first decreasing and then increasing. The correlation results indicated a significant correlation (0.977) between TN and TP emissions in wastewater in China during 2011-2020. Through clustering and Multidimensional Scaling model (MDS) analysis, Beijing and Shanghai have been performing well in controlling water pollution discharge, while the provinces of Tibet and Guangxi must still increase their efforts in water pollution control. Furthermore, these results demonstrate the experience and achievements of the Chinese government in the treatment of wastewater pollution and provide a useful reference for treatment of wastewater pollution in the world.

Effects of feeding methods on growth and slaughter performance, blood biochemical indices, and intestinal morphology in Minxinan black rabbits (Oryctolagus cuniculus).

Feed restriction after weaning is a common strategy used in commercial rabbit farms to improve feed efficiency, promote health, and reduce mortality. However, few studies have investigated the feed restrictions of Minxinan black rabbits (Oryctolagus cuniculus). Thus, the effects of feed restriction on growth and slaughter performance, intestinal morphology, and blood biochemical indices of Minxinan black rabbits were evaluated in this study. Rabbits in group A (control group) had ad libitum intake, while those in feed restriction groups (groups B, C, and D) were restricted to 80% of the average daily feed intake (ADFI) of group A the day before. The rabbits in group B were fed once per day at 8:00 am. Rabbits in groups C and D were fed twice per day at 8:00 am (50%) and 4:00 pm (50%) and 8:00 am (30%) and 4:00 pm (70%), respectively. The experimental period lasted for 8 weeks. Compared to that in group A, the diarrhea rate of group C was significantly decreased (P < 0.05), and the ADFI, feed conversion ratio, abdominal fat weight, abdominal fat rate, total protein, albumin, globulin, alanine aminotransferase (ALT), low-density lipoprotein, and intestinal crypt depth of all feed restriction groups were significantly reduced (P < 0.01). Feed conversion ratio in group D was significantly better than that in groups B and C (P < 0.05). The efficiency index (EI) of groups C and D was higher than that of groups A and B (P < 0.01). Triglyceride levels in groups C and D were significantly lower than those in group A. The villus length to crypt depth of the duodenum and jejunum in group D was significantly higher than that in group A (P < 0.01). In conclusion, the following parameters can be improved by feed restriction: feed conversion ratio, diarrhea rate, abdominal fat rate, serum ALT, lipid indices and intestinal health of Minxinan black rabbits, and the EI of the farm. Feeding twice per day, 30% at 8:00 am and 70% at 4:00 pm, had the best comprehensive effects.

The Sponge Interaction Between Circular RNA and microRNA Serves as a Fast-Evolving Mechanism That Suppresses Non-small Cell Lung Cancer (NSCLC) in Humans.

Non-small cell lung cancer (NSCLC) is one of the most lethal cancer types in the world. Currently, the molecular mechanisms and pathways underlying NSCLC oncogenesis are poorly understood. Using multiple Omics data, we systematically explored the differentially expressed circular RNAs (circRNAs) in NSCLC. We also investigated potential microRNA sponges (that absorb circRNAs) in NSCLC and downstream target genes with experimental verifications. hsa_circ_0003497 was down-regulated in NSCLC and played an inhibitory role in tumorigenesis. In contrast, miR-197-3p was up-regulated in NSCLC. hsa_circ_0003497 directly interacts with miR-197-3p and releases a target gene of miR-197-3p termed CTNND1 (a known tumor suppressor gene). Evolutionary analysis reveals fast evolution of this hsa_circ_0003497-miR-197-3p-CTNND1-NSCLC axis in mammals. This work clarified the biological functions and molecular mechanisms of how hsa_circ_0003497 suppresses NSCLC through miR-197-3p and CTNND1. We discovered molecular markers for the prognosis of NSCLC and provided potential intervention targets for its treatment.

Pathogenic and genomic characterisation of a rabbit sourced Pasteurella multocida serogroup F isolate s4.

BACKGROUND: Pasteurella multocida is one of the most significant pathogens for a number of animals. In rabbits, the infection is generally associated with the P. multocida serogroups A and D, and the knowledge about the serogroup F is limited. In the present study, a P. multocida serogroup F isolate designated s4 was recovered from the lungs of rabbits died of respiratory disease in Fujian, in the southeast of China. The pathogenicity and genomic features of the s4 were then determined. RESULTS: The serotype and sequence type of s4 were F:L3 and ST12, respectively. The s4 was pathogenic for rabbits, but it was a low virulent strain comparing to the previously reported highly pathogenic P. multocida serogroup F strains J-4103, C21724H3km7, P-4218 and HN07. The whole genome of the s4 was then sequenced to understand the genomic basis for pathogenicity. Particularly, a large-sized fragment of approximate 275 kb in length was truncated from the chromosome to form a plasmid. Moreover, the in-frame deletion of natC and N-terminal redundance of gatF would resulted in the production of a mutant L3 outer core structure that was distinct from those of the other P. multocida strains belonging to the lipopolysaccharide genotype L3. We deduced that these features detected in the genome of s4 might impair the pathogenicity of the bacterium. CONCLUSIONS: This study evaluated the pathogenicity and determined the genomic features of the rabbit sourced P. multocida serogroup F isolate s4, the observations and findings would helpful for the understanding of the pathogenicity variability and genetic diversity of P. multocida.

Re-interpretation of the mechanism of type 2 diabetes mellitus based on a framework of psychosomatic medicine: a real-world study.

OBJECTIVE: Using bipolar disorder (BD) as a control, we explored the possible developmental process of impaired glucose metabolism rhythm. METHODS: In total, 441 subjects (77, 162, 134, 54, and 14 in the pre-diabetes [pre-DM], DM, BD, BD + pre-DM, and BD + DM groups, respectively) and 160 controls were included. All subjects were assessed using the Neuroticism Extraversion Openness Five-Factor Inventory (NEO-FFI). The hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-thyroid (HPT) axes were measured. RESULTS: Cluster analysis showed that the BD, BD + DM, and DM groups were classified as the 'disease group, the BD + pre-DM group as the 'mixed period group', and the pre-DM group as the 'pre-disease group'. The conscientiousness factor scores of the NEO-FFI in the 'disease group' were higher than the norm but lower than the norm in the 'pre-disease group'. The scores of neurotic factors in the 'pre-disease' and 'mixed period' groups were both significantly higher than that in the 'disease group' (corrected p < 0.001). The incidences of the abnormal HPA axis decreased gradually from the 'pre-disease group' to the 'mixed period group' then to the 'disease group', while those of the HPT axis slightly increased at first and then significantly decreased. The overall prediction rate of the multiple logistic regression model was 92.7%. CONCLUSION: This study suggests that progression of pre-diabetes to DM is a continuous process from local abnormalities to rhythm disorder of glucose metabolism. This understanding can be applied to the whole course management and early intervention of DM and to the future development of optimised treatment based on rhythm regulation. TRIAL REGISTRATION: Clinical trial registration number: ChiCTR1800019064. Name of trial registration: Identify and the optimization of treatment for non-infectious chronic diseases under the "stress-dysrhythmia" theory hypothesis (Registration date: 24/10/2018). The full trial protocol can be accessed at the Chinese Clinical Trial Registry ( http://www.chictr.org.cn/ ).

CDC48B facilitates the intercellular trafficking of SHORT-ROOT during radial patterning in roots.

CELL DIVISION CONTROL PROTEIN48 (CDC48) is essential for membrane fusion, protein degradation, and other cellular processes. Here, we revealed the crucial role of CDC48B in regulating periclinal cell division in roots by analyzing the recessive gen1 mutant. We identified the GEN1 gene through map-based cloning and verified that GEN1 encodes CDC48B. gen1 showed severely inhibited root growth, increased periclinal cell division in the endodermis, defective middle cortex (MC) formation, and altered ground tissue patterning in roots. Consistent with these phenotypes, CYCLIND 6;1(CYCD6;1), a periclinal cell division marker, was upregulated in gen1 compared to Col-0. The ratio of SHRpro :SHR-GFP fluorescence in pre-dividing nuclei versus the adjacent stele decreased by 33% in gen1, indicating that the trafficking of SHORT-ROOT (SHR) decreased in gen1 when endodermal cells started to divide. These findings suggest that the loss of function of CDC48B inhibits the intercellular trafficking of SHR from the stele to the endodermis, thereby decreasing SHR accumulation in the endodermis. These findings shed light on the crucial role of CDC48B in regulating periclinal cell division in roots.

Establishment of a Systemic Inflammatory Response Syndrome Model and Evaluation of the Efficacy of Umbilical Cord Mesenchymal Stem Cell Transplantation.

Based on the characteristics of modern weapon injury, a repetitive model of traumatic systemic inflammatory response syndrome (SIRS) and an evaluation system were established. The models were treated with GFP-labeled tree shrew umbilical cord mesenchymal stem cells (UCMSCs). Forty out of 50 tree shrews were used to make a unilateral femoral comminuted fracture. Lipopolysaccharide was injected intravenously to create a traumatic SIRS model. The other 10 shrews were used as normal controls. After the model was established for 10 days, 20 tree shrews were injected intravenously with GFP-labeled UCMSCs, and 18 tree shrews were not injected as the model control group. The distribution of GFP-labeled cells in vivo was measured at 2 and 10 days after injection. Twenty days after treatment, the model group, the normal control group, and the treatment group were taken to observe the pathological changes in each tissue, and blood samples were taken for the changes in liver, renal, and heart function. Distribution of GFP-positive cells was observed in all tissues at 2 and 10 days after injection. After treatment, the HE staining results of the treatment group were close to those of the normal group, and the model group had a certain degree of lesions. The results of liver, renal, and heart function tests in the treatment group were returned to normal, and the results in the model group were abnormally increased. UCMSCs have a certain effect on the treatment of traumatic SIRS and provide a new technical solution for modern weapon trauma treatment.

Characteristics of viral pneumonia in non-HIV immunocompromised and immunocompetent patients: a retrospective cohort study.

BACKGROUND: Concerning viral pneumonia, few large-scale comparative studies have been published describing non-HIV immunocompromised and immunocompetent patients, but the epidemiological characteristics of different viruses or underlying diseases in immunocompromised hosts are lacking. METHODS: We retrospectively recruited patients hospitalised with viral pneumonia from six academic hospitals in China between August 2016 and December 2019. We measured the prevalence of comorbidities, coinfections, nosocomial infections, and in-hospital mortalities. RESULTS: Of the 806 patients, 370 were immunocompromised and 436 were immunocompetent. The disease severity and in-hospital mortality of immunocompromised patients were higher than those of immunocompetent patients. During the influenza season, an increased number of cases of influenza virus (IFV) infection were found in the immunocompromised group, followed by cases of cytomegalovirus (CMV) and respiratory syncytial virus (RSV) infection. During the non-influenza season, CMV was the main virus detected in the immunocompromised group, while RSV, adenovirus (AdV), parainfluenza virus (PIV), and rhinovirus (HRV) were the main viruses detected in the immunocompetent group. Pneumonia caused by Pneumocystis jirovecii (22.4%), Aspergillus spp. (14.1%), and bacteria (13.8%) were the most frequently observed coinfections in immunocompromised patients but not in immunocompetent patients (Aspergillus spp. [10.8%], bacteria [7.1%], and Mycoplasma spp. [5.3%]). CMV infection and infection with two-or-more viruses were associated with a higher in-hospital mortality rate than non-IFV infection. However, patients with IFV and non-IFV infection in immunocompromised patients had similar disease severity and prognosis. CONCLUSIONS: Immunocompromised patients have a high frequency of coinfections, and a higher mortality rate was observed among those infected with CMV and two-or-more viruses. In addition, patients with IFV and non-IFV infection in immunocompromised patients had similar same disease severity and prognosis. The type of viral infection varied with seasons.

Duration of antibiotic treatment using procalcitonin-guided treatment algorithms in older patients: a patient-level meta-analysis from randomized controlled trials.

BACKGROUND: Older patients have a less pronounced immune response to infection, which may also influence infection biomarkers. There is currently insufficient data regarding clinical effects of procalcitonin (PCT) to guide antibiotic treatment in older patients. OBJECTIVE AND DESIGN: We performed an individual patient data meta-analysis to investigate the association of age on effects of PCT-guided antibiotic stewardship regarding antibiotic use and outcome. SUBJECTS AND METHODS: We had access to 9,421 individual infection patients from 28 randomized controlled trials comparing PCT-guided antibiotic therapy (intervention group) or standard care. We stratified patients according to age in four groups (<75 years [n = 7,079], 75-80 years [n = 1,034], 81-85 years [n = 803] and >85 years [n = 505]). The primary endpoint was the duration of antibiotic treatment and the secondary endpoints were 30-day mortality and length of stay. RESULTS: Compared to control patients, mean duration of antibiotic therapy in PCT-guided patients was significantly reduced by 24, 22, 26 and 24% in the four age groups corresponding to adjusted differences in antibiotic days of -1.99 (95% confidence interval [CI] -2.36 to -1.62), -1.98 (95% CI -2.94 to -1.02), -2.20 (95% CI -3.15 to -1.25) and - 2.10 (95% CI -3.29 to -0.91) with no differences among age groups. There was no increase in the risk for mortality in any of the age groups. Effects were similar in subgroups by infection type, blood culture result and clinical setting (P interaction >0.05). CONCLUSIONS: This large individual patient data meta-analysis confirms that, similar to younger patients, PCT-guided antibiotic treatment in older patients is associated with significantly reduced antibiotic exposures and no increase in mortality.