A Novel Probiotic-Based Oral Vaccine against SARS-CoV-2 Omicron Variant B.1.1.529.

COVID-19 pandemic, caused by the SARS-CoV-2 virus, is still affecting the entire world via the rapid emergence of new contagious variants. Vaccination remains the most effective prevention strategy for viral infection, yet not all countries have sufficient access to vaccines due to limitations in manufacturing and transportation. Thus, there is an urgent need to develop an easy-to-use, safe, and low-cost vaccination approach. Genetically modified microorganisms, especially probiotics, are now commonly recognized as attractive vehicles for delivering bioactive molecules via oral and mucosal routes. In this study, Lactobacillus casei has been selected as the oral vaccine candidate based on its' natural immunoadjuvant properties and the ability to resist acidic gastric environment, to express antigens of SARS-CoV-2 Omicron variant B.1.1.529 with B-cell and T-cell epitopes. This newly developed vaccine, OMGVac, was shown to elicit a robust IgG systemic immune response against the spike protein of Omicron variant B.1.1.529 in Golden Syrian hamsters. No adverse effects were found throughout this study, and the overall safety was evaluated in terms of physiological and histopathological examinations of different organs harvested. In addition, this study illustrated the use of the recombinant probiotic as a live delivery vector in the initiation of systemic immunity, which shed light on the future development of next-generation vaccines to combat emerging infectious diseases.

Blocking protease-activated receptor 4 alleviates liver injury induced by brain death.

Brain death (BD) induces a systemic inflammatory response that influences donor liver quality. Protease-activated receptor 4 (PAR4) is a thrombin receptor that mediates platelet activation and is involved in inflammatory and apoptotic processes. Therefore, we investigated the role of PAR4 blockade in liver injury induced by BD and its associated mechanisms. In this study, we constructed a BD rat model and treated rats with TcY-NH2, a selective PAR4 antagonist, to block PAR4 signaling at the onset of BD induction. Our results revealed that PAR4 protein expression increased in the livers of rats with BD. PAR4 blockade alleviated liver injury induced by BD, as indicated by lower serum ALT/AST levels and an improvement in histomorphology. Blood platelet activation and hepatic platelet accumulation in BD rats were reduced by PAR4 blockade. Additionally, PAR4 blockade attenuated the inflammatory response and apoptosis in the livers of BD rats. Moreover, the activation of NF-κB and MAPK pathways induced by BD was inhibited by PAR4 blockade. Thus, our results suggest that PAR4 contributes to liver injury induced by BD by regulating inflammation and apoptosis through the NF-κB and MAPK pathways. Thus, PAR4 blockade may provide a feasible approach to improve the quality of organs from BD donors.

Expanding the clinicopathological spectrum of succinate dehydrogenase-deficient renal cell carcinoma with a focus on variant morphologies: a study of 62 new tumors in 59 patients.

Most succinate dehydrogenase (SDH)-deficient renal cell carcinomas (RCCs) demonstrate stereotypical morphology characterized by bland eosinophilic cells with frequent intracytoplasmic inclusions. However, variant morphologic features have been increasingly recognized. We therefore sought to investigate the incidence and characteristics of SDH-deficient RCC with variant morphologies. We studied a multi-institutional cohort of 62 new SDH-deficient RCCs from 59 patients. The median age at presentation was 39 years (range 19-80), with a slight male predominance (M:F = 1.6:1). A relevant family history was reported in 9 patients (15%). Multifocal or bilateral tumors were identified radiologically in 5 patients (8%). Typical morphology was present at least focally in 59 tumors (95%). Variant morphologies were seen in 13 (21%) and included high-grade nuclear features and various combinations of papillary, solid, and tubular architecture. Necrosis was present in 13 tumors, 7 of which showed variant morphology. All 62 tumors demonstrated loss of SDHB expression by immunohistochemistry. None showed loss of SDHA expression. Germline SDH mutations were reported in all 18 patients for whom the results of testing were known. Among patients for whom follow-up data was available, metastatic disease was reported in 9 cases, 8 of whom had necrosis and/or variant morphology in their primary tumor. Three patients died of disease. In conclusion, variant morphologies and high-grade nuclear features occur in a subset of SDH-deficient RCCs and are associated with more aggressive behavior. We therefore recommend grading all SDH-deficient RCCs and emphasize the need for a low threshold for performing SDHB immunohistochemistry in any difficult to classify renal tumor, particularly if occurring at a younger age.

Traditional Chinese Nursing Using Fennel With Coarse Salt for Ironing and Umbilical Moxibustion for Epigastric Pain With Spleen-stomach Vacuity Cold.

Context: Spleen-stomach vacuity cold is the primary TCM pattern for epigastric pain, accounting for 75% of the patients. According to the TCM theory of treating both the tip and the root, epigastric pain requires the caregiver to dissipate cold and relieve pain, the treatments for the tip, which warm and supplement the spleen and stomach, the treatments for the root. Objective: This study aimed to explore effectiveness of traditional Chinese nursing care using fennel mixed with coarse salt for ironing,with umbilical moxibustion, for epigastric pain, with a pattern of spleen-stomach vacuity cold. Design: The research team designed a randomized control trial (RCT). Setting: The study was conducted at Ruikang Affiliated Hospital of Guangxi University of Chinese Medicine in the capital city of the Guangxi Zhuang autonomous region in the People's Republic of China. Participants: Participants were 96 patients who had been admitted to the hospital between October and November 2020 with epigastric pain resulting from the TCM spleen-stomach vacuity cold pattern, equivalent to chronic atrophic gastritis in Western medicine. Intervention: The research team randomly divided participants into an intervention group (n = 48) and a control group (n = 48) using a random digits table. The intervention group received fennel mixed with coarse salt for ironing, combined with umbilical moxibustion, whereas the control group received routine care. Outcome Measures: The study's instruments included the Traditional Chinese Medicine (TCM) Syndrome Score Scale (TCMSSS), Medical Outcome Study (MOS) Short Form 36 (SF-36), and Satisfaction with TCM Nursing Program (STCMNP). Data were collected and analyzed through descriptive statistics a Chi-square test and independent t test. A significance level of P < .05 was accepted for all statistical analyses. Results: The intervention group had mean scores that indicated significantly higher decreases in epigastric pain, and increases in quality of life and level of satisfaction with the traditional Chinese nursing care than the control group did (P < .05). Conclusions: The traditional Chinese nursing care was able to improve epigastric pain, enhance quality of life, and increase satisfaction with the traditional Chinese nursing care.

Six-Transmembrane Epithelial Antigen of the Prostate 3 Deficiency in Hepatocytes Protects the Liver Against Ischemia-Reperfusion Injury by Suppressing Transforming Growth Factor-ß-Activated Kinase 1.

BACKGROUND AND AIMS: Hepatic ischemia-reperfusion (I/R) injury remains a major challenge affecting the morbidity and mortality of liver transplantation. Effective strategies to improve liver function after hepatic I/R injury are limited. Six-transmembrane epithelial antigen of the prostate 3 (Steap3), a key regulator of iron uptake, was reported to be involved in immunity and apoptotic processes in various cell types. However, the role of Steap3 in hepatic I/R-induced liver damage remains largely unclear. APPROACH AND RESULTS: In the present study, we found that Steap3 expression was significantly up-regulated in liver tissue from mice subjected to hepatic I/R surgery and primary hepatocytes challenged with hypoxia/reoxygenation insult. Subsequently, global Steap3 knockout (Steap3-KO) mice, hepatocyte-specific Steap3 transgenic (Steap3-HTG) mice, and their corresponding controls were subjected to partial hepatic warm I/R injury. Hepatic histology, the inflammatory response, and apoptosis were monitored to assess liver damage. The molecular mechanisms of Steap3 function were explored in vivo and in vitro. The results demonstrated that, compared with control mice, Steap3-KO mice exhibited alleviated liver damage after hepatic I/R injury, as shown by smaller necrotic areas, lower serum transaminase levels, decreased apoptosis rates, and reduced inflammatory cell infiltration, whereas Steap3-HTG mice had the opposite phenotype. Further molecular experiments showed that Steap3 deficiency could inhibit transforming growth factor-ß-activated kinase 1 (TAK1) activation and downstream c-Jun N-terminal kinase (JNK) and p38 signaling during hepatic I/R injury. CONCLUSIONS: Steap3 is a mediator of hepatic I/R injury that functions by regulating inflammatory responses as well as apoptosis through TAK1-dependent activation of the JNK/p38 pathways. Targeting hepatocytes, Steap3 may be a promising approach to protect the liver against I/R injury.

Periodontal disease and emotional disorders: A meta-analysis.

OBJECTIVE: The objective of this study was to evaluate the relationship of periodontal disease with depression and anxiety via a systematic review and meta-analysis. METHOD: We systematically searched the EMBASE, PubMed, Web of Science, PsycINFO, and SinoMed databases (until August 4, 2019) with language restricted to English and Chinese. Case-control, cross-sectional, and cohort studies that calculated the risk ratio (RR), odds ratio (OR)/prevalence OR (POR), and hazard ratio (HR) of depression/anxiety with periodontal disease or the OR/POR/RR/HR of periodontal disease caused by depression/anxiety were included. Observational studies that reported the depression/anxiety scale score of patients with periodontal disease and healthy periodontal subjects aged ≥14 years were also included. We used the standard format to extract the following information from each included study: author/s, survey year, study design, age of participants, periodontal disease definition, depression/anxiety measurement, and summary of results. The Newcastle-Ottawa scale was used to ascertain the quality of the included citations. RESULTS: After screening, 40 studies were included. A meta-analysis of the case-control studies showed that periodontal disease was positively associated with depression (OR = 1.70, 95% confidence interval [CI] â€Š= 1.01-2.83). A meta-analysis of 12 studies showed that periodontal disease was significantly correlated with anxiety (OR = 1.36, 95% CI = 1.11-1.66). A meta-analysis of 18 studies showed that subjects with periodontal disease had higher depression scale score (standardized mean difference [SMD] = 1.05, 95% CI = 0.68-1.41) and anxiety scale score (SMD = 0.70, 95% CI = 0.44-0.96). CONCLUSION: Periodontal disease is associated with emotional disorders. However, the high degree of heterogeneity among studies should be considered. More high-quality prospective studies are required to confirm the relationship.

Porphyromonas gingivalis induces depression via downregulating p75NTR-mediated BDNF maturation in astrocytes.

Many cross-sectional epidemiological studies have shown the incidence of periodontitis is positive correlated with that of depression. However, their causal relationship and underlying mechanism are largely unknown. Porphyromonas gingivalis (Pg) is the main pathogen for periodontitis. Employing female mice treated with Pg every other day for 4 weeks, we found that Pg-mice showed obvious depression-like behavior, an increased number of activated astrocytes and decreased levels of mature brain derived neurotrophic factor (BDNF) and astrocytic p75NTR in the hippocampus. Both hippocampal injection of BDNF and overexpression of p75NTR in astrocytes alleviated Pg-induced depression-like behavior in mice. Moreover, Pg-lipopolysaccharides (LPS) generated similar phenotypes, which were reversed by the TLR-4 inhibitor TAK242. Our results suggest that Pg-LPS decreases the level of astrocytic p75NTR and then downregulates BDNF maturation, leading to depression-like behavior in mice. Our study provides the first evidence that Pg is a modifiable risk factor for depression and uncovers a novel therapeutic target for the treatment of depression.

Ameliorative effect of sevoflurane on endoplasmic reticulum stress mediates cardioprotection against ischemia-reperfusion injury 1.

We aimed to investigate whether the cardioprotection of sevoflurane against ischemia-reperfusion (IR) injury is via inhibiting endoplasmic reticulum stress. The rat in vivo model of myocardial IR injury was induced by ligation of the left anterior descending coronary artery. Sevoflurane significantly ameliorated the reduced cardiac function, increased infarct size, and elevated troponin I level and lactate dehydrogenase activity in plasma induced by IR injury. Sevoflurane suppressed the IR-induced myocardial apoptosis. The increased protein levels of glucose-regulated protein 78 and C/EBP homologous protein (CHOP) after myocardial IR were significantly reduced by sevoflurane. The protein levels of phosphorylated protein kinase RNA-like endoplasmic reticulum kinase (PERK), phosphorylated eukaryotic initiation factor 2 (eIF2α), and activating transcription factor 4 (ATF4) were significantly increased in rats with IR and attenuated by sevoflurane treatment. The phosphorylation of Akt was further activated by sevoflurane. The cardioprotection of sevoflurane could be blocked by wortmannin, a PI3K/Akt inhibitor. Our results suggest that the cardioprotection of sevoflurane against IR injury might be mediated by suppressing PERK/eIF2a/ATF4/CHOP signaling via activating the Akt pathway, which helps in understanding the novel mechanism of the cardioprotection of sevoflurane.

Endovascular interventional modalities for haemorrhage control in abnormal placental implantation deliveries: a systematic review and meta-analysis.

OBJECTIVES: To examine the evidence regarding the effectiveness and safety of endovascular interventional modalities for haemorrhage control in abnormal placentation deliveries. METHODS: MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched from inception to July 2017. Blood loss volume was regarded as the primary endpoint. Other important results are described. Random and fixed effects models were used for the meta-analysis. RESULTS: Of 385 studies identified, 69 (1,811 patients, mean age 32.9 years, range 23-39 years) were included. Mean gestational age at delivery was 35.1 weeks (range 27-38 weeks). Of 1,395 patients who underwent endovascular intervention, 587 (42%) had placenta accreta, 254 (18%) placenta increta and 313 (22%) placenta percreta. Prophylactic balloon occlusion of the internal iliac arteries (PBOIIA) was performed in 470 patients (33.6%), of the abdominal aorta (PBOAA) in 460 patients (33%), of the uterine artery (PBOUA) in 181 patients (13%), and of the common iliac arteries (PBOCIA) in 21 patients (1.5%). Primary embolization of the UA was performed in 246 patients (18%), of the pelvic collateral arteries in 12 patients (0.9%), and of the anterior division of the IIA in 5 patients (0.3%). Follow-up ranged from 0.5 to 42 months. Endovascular intervention was associated with less blood loss than no endovascular intervention (p < 0.001) with the lowest blood loss volume in patients who underwent PBOAA (p < 0.001). PBOAA was associated with a lower rate of hysterectomy (p = 0.030). Endovascular intervention did not result in increases in operative time or hospital stay. CONCLUSIONS: Endovascular intervention is effective in controlling haemorrhage in abnormal placentation deliveries. PBOAA was associated with a lower rate of hysterectomy and less blood loss than other modalities. KEY POINTS: • Endovascular intervention in abnormal placentation deliveries is effective in reducing blood loss. • Endovascular intervention did not result in longer operative time or hospital stay. • Prophylactic balloon occlusion of the abdominal aorta is superior to other modalities.

A methodology review on the incremental prognostic value of computed tomography biomarkers in addition to Framingham risk score in predicting cardiovascular disease: the use of association, discrimination and reclassification.

BACKGROUND: Computed tomography (CT) biomarkers claim to improve cardiovascular risk stratification. This review focuses on significant differences in incremental measures between adequate and inadequate reporting practise. METHODS: Studies included were those that used Framingham Risk Score as a baseline and described the incremental value of adding calcium score or CT coronary angiogram in predicting cardiovascular risk. Searches of MEDLINE, EMBASE, Web of Science and Cochrane Central were performed with no language restriction. RESULTS: Thirty five studies consisting of 206,663 patients (men = 118,114, 55.1%) were included. The baseline Framingham Risk Score included the 1998, 2002 and 2008 iterations. Selective reporting, inconsistent reference groupings and thresholds were found. Twelve studies (34.3%) had major and 23 (65.7%) had minor alterations and the respective Δ AUC were significantly different (p = 0.015). When the baseline model performed well, the Δ AUC was relatively lower with the addition of a CT biomarker (Spearman coefficient = - 0.46, p < 0.0001; n = 33; 76 pairs of data). Other factors that influenced AUC performance included exploration of data analysis, calibration, validation, multivariable and AUC documentation (all p < 0.05). Most studies (68.7%) that reported categorical NRI (n = 16; 46 pairs of data) subjectively drew strong conclusions along with other poor reporting practices. However, no significant difference in values of NRI was found between adequate and inadequate reporting. CONCLUSIONS: The widespread practice of poor reporting particularly association, discrimination, reclassification, calibration and validation undermines the claimed incremental value of CT biomarkers over the Framingham Risk Score alone. Inadequate reporting of discrimination inflates effect estimate, however, that is not necessarily the case for reclassification.

Intra-patient comparison of reduced-dose model-based iterative reconstruction with standard-dose adaptive statistical iterative reconstruction in the CT diagnosis and follow-up of urolithiasis.

OBJECTIVES: To evaluate the accuracy of reduced-dose CT scans reconstructed using a new generation of model-based iterative reconstruction (MBIR) in the imaging of urinary tract stone disease, compared with a standard-dose CT using 30% adaptive statistical iterative reconstruction. METHODS: This single-institution prospective study recruited 125 patients presenting either with acute renal colic or for follow-up of known urinary tract stones. They underwent two immediately consecutive scans, one at standard dose settings and one at the lowest dose (highest noise index) the scanner would allow. The reduced-dose scans were reconstructed using both ASIR 30% and MBIR algorithms and reviewed independently by two radiologists. Objective and subjective image quality measures as well as diagnostic data were obtained. RESULTS: The reduced-dose MBIR scan was 100% concordant with the reference standard for the assessment of ureteric stones. It was extremely accurate at identifying calculi of 3 mm and above. The algorithm allowed a dose reduction of 58% without any loss of scan quality. CONCLUSIONS: A reduced-dose CT scan using MBIR is accurate in acute imaging for renal colic symptoms and for urolithiasis follow-up and allows a significant reduction in dose. KEY POINTS: • MBIR allows reduced CT dose with similar diagnostic accuracy • MBIR outperforms ASIR when used for the reconstruction of reduced-dose scans • MBIR can be used to accurately assess stones 3 mm and above.

Stigmatic exudate in the Annonaceae: Pollinator reward, pollen germination medium or extragynoecial compitum?

Although "dry-type" stigmas are widely regarded as ancestral in angiosperms, the early-divergent family Annonaceae has copious stigmatic exudate. We evaluate three putative functions for this exudate: as a nutritive reward for pollinators; as a pollen germination medium; and as an extragynoecial compitum that enables pollen tube growth between carpels. Stigmatic exudate is fructose dominated (72.2%), but with high levels of glucose and sucrose; the dominance of hexose sugars and the diversity of amino acids observed, including many that are essential for insects, support a nutritive role for pollinators. Sugar concentration in pre-receptive flowers is high (28.2%), falling during the peak period of stigmatic receptivity (17.4%), and then rising again toward the end of the pistillate phase (32.9%). Pollen germination was highest in sugar concentrations <20%. Sugar concentrations during the peak pistillate phase therefore provide optimal osmolarity for pollen hydration and germination; subsequent changes in sugar concentration during anthesis reinforce protogyny (in which carpels mature before stamens), enabling the retention of concentrated exudate into the staminate phase as a pollinator food reward without the possibility of pollen germination. Intercarpellary growth of pollen tubes was confirmed: the exudate therefore also functions as a suprastylar extragynoecial compitum, overcoming the limitations of apocarpy.

Drastic reduction of plastome size in the mycoheterotrophic Thismia tentaculata relative to that of its autotrophic relative Tacca chantrieri.

PREMISE OF THE STUDY: Heterotrophic angiosperms tend to have reduced plastome sizes relative to those of their autotrophic relatives because genes that code for proteins involved in photosynthesis are lost. However, some plastid-encoded proteins may have vital nonphotosynthetic functions, and the plastome therefore may be retained after the loss of photosynthesis. METHODS: We sequenced the plastome of the mycoheterotrophic species Thismia tentaculata and a representative of its sister genus, Tacca chantrieri, using next-generation technology, and we compared sequences and structures of genes and genomes of these species. KEY RESULTS: The plastome of Tacca chantrieri is similar to those of other autotrophic taxa of Dioscoreaceae, except in a few local rearrangements and one gene loss. The plastome of Thismia tentaculata is ca. 16 kbp long with a quadripartite structure and is among the smallest known plastomes. Synteny is minimal between the plastomes of Tacca chantrieri and Thismia tentaculata. The latter includes only 12 candidate genes, with all except accD involved in protein synthesis. Of the 12 genes, trnE, trnfM, and accD are frequently among the few that remain in depauperate plastomes. CONCLUSIONS: The plastome of Thismia tentaculata, like those of most other heterotrophic plants, includes a small number of genes previously suggested to be essential to plastome survival.

Molecular simulation assisted identification of Ca(2+) binding residues in TMEM16A.

Calcium-activated chloride channels (CaCCs) play vital roles in a variety of physiological processes. Transmembrane protein 16A (TMEM16A) has been confirmed as the molecular counterpart of CaCCs which greatly pushes the molecular insights of CaCCs forward. However, the detailed mechanism of Ca(2+) binding and activating the channel is still obscure. Here, we utilized a combination of computational and electrophysiological approaches to discern the molecular mechanism by which Ca(2+) regulates the gating of TMEM16A channels. The simulation results show that the first intracellular loop serves as a Ca(2+) binding site including D439, E444 and E447. The experimental results indicate that a novel residue, E447, plays key role in Ca(2+) binding. Compared with WT TMEM16A, E447Y produces a 30-fold increase in EC50 of Ca(2+) activation and leads to a 100-fold increase in Ca(2+) concentrations that is needed to fully activate the channel. The following steered molecular dynamic (SMD) simulation data suggests that the mutations at 447 reduce the Ca(2+) dissociation energy. Our results indicated that both the electrical property and the size of the side-chain at residue 447 have significant effects on Ca(2+) dependent gating of TMEM16A.

Proteomic profiling of N-linked glycoproteins identifies ConA-binding procathepsin D as a novel serum biomarker for hepatocellular carcinoma.

The aim of this study was to identify novel biomarkers for the diagnosis of, and potential therapeutic targets for, hepatocellular carcinoma (HCC). Multilectin affinity chromatography was used to enrich N-linked glycoproteins from nontumorous liver and HCC tissues followed by 2DE and protein identification by MS. Twenty-eight differentially expressed proteins were identified. Western blotting validated consistently lower concentrations of human liver carboxylesterase 1 and haptoglobin, and higher concentration of procathepsin D (pCD) in HCC tissues. Knockdown of cathepsin D (CD) expression mediated by siRNA significantly inhibited the in vitro invasion of two HCC cell lines, SNU449 and SNU473, which normally secrete high-levels of CD. Prefractionation using individual lectins demonstrated an elevation in ConA-binding glycoforms of proCD and CD in HCC tissues. In the serum of HCC patients, "ConA-binding proCD" (ConA-pCD) is significantly increased in concentration and this increase is comprised of several distinct upregulated acidic isoforms (pI 4.5-5.5). Receiver operating characteristic analysis showed that the sensitivity and specificity of serum ConA-pCD for HCC diagnosis were 85% and 80%, respectively. This is the first report that serum ConA-pCD is increased significantly in HCC and is potentially useful as a serological biomarker for diagnosis of HCC.

FXR1 promotes proliferation, invasion and migration of hepatocellular carcinoma in vitro and in vivo.

Hepatocellular carcinoma (HCC) is a common malignancy that is associated with a poor prognosis. The extensively studied TGF-ß pathway is mediated by SMAD proteins. FXR1, a protein-coding gene belonging to the fragile X-related (FXR) family, is involved in the TGF-ß pathway. Previous studies have shown that FXR1 promotes the proliferation, invasion, and migration of colorectal cancer cells. The aim of the present study was to explore the effects of FXR1 on HCC via the TGF-ß/SMAD signaling pathway. Immunohistochemical analysis was used to detect the expression of FXR1 in HCC and normal tissues. Western blotting was used to detect protein expression levels in the HCC cell lines, cell migration and invasion were assessed using Transwell assays, and cell proliferation was assessed using a colony formation assay. The ability of the liver cancer cells to grow in vivo was investigated using a nude mouse tumor-bearing model. The results showed that FXR1 expression was upregulated in HCC tissues compared with normal tissues. Knockdown of FXR1 resulted in reduced expression of SMAD2/3 and EMT-related proteins in HCC cells. In addition, FXR1 knockdown inhibited the proliferation, migration, and invasion of HCC cells. FXR1 knockdown also reversed the promoting effect of TGF-ß on the invasive ability of HCC cells. Knockdown of SMAD2/3 reversed the increase in HCC cell invasion induced by FXR1 overexpression. Finally, upregulated FXR1 expression was associated with a poorer prognosis in patients with HCC. In conclusion, FXR1 promoted HCC proliferation, migration, and invasion through the regulation of SMAD2/3.

Characterization of the Gut Microbiome in Healthy Dogs and Dogs with Diabetes Mellitus.

With a close pathogenetic resemblance to human diabetes, canine Diabetes Mellitus, a chronic metabolic disease featuring abnormally high blood sugar levels, is increasing in prevalence worldwide. Unlike humans, canine glycemic control requires life-long insulin injections and dietary control in most cases, thereby jeopardizing diabetic dogs' quality of life and increasing the difficulty of disease control. While many research studies have focused on elucidating the relationship between the canine gut microbiome and diseases, there is currently no research on the subject of diabetes mellitus in dogs. We hypothesized that the gut microbiome of canines with diabetes mellitus is different from that of healthy controls. Thus, we performed targeted 16S rRNA sequencing and comprehensive bioinformatic analysis to compare the gut microbiome profiles of 16 diabetic dogs with those of 32 healthy dogs. Clostridioides difficile, Phocaeicola plebeius, Lacrimispora indolis, and Butyricicoccus pullicaecorum were found to be enriched in diabetic dogs. A distinct shift towards carbohydrate degradation metabolic pathways was found to be differentially abundant in the diabetic subjects. Alteration of the co-occurrence network was also evident in the diabetic group. In conclusion, our study suggests that the gut microbial landscape differs in diabetic canines at the genera, species, functional, and network levels. These findings have significant implications for disease management, and thus warrant further research.

[Role of glucocorticoid receptor in the pathogenesis of systemic lupus erythematosus].

OBJECTIVE: To investigate the expressions of GRα mRNA and GRß mRNA in the peripheral blood mononuclear cells (PBMCs) of systemic lupus erythematosus (SLE) patients, in order to reveal the role of GR mRNA in the pathogenesis of SLE and analyze the relationship between GR mRNA and SLEDAI score, dsDNA, cardiovascular involvement. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) technique was applied to semiquantitatively analyze GRα mRNA and GRß mRNA expressions in 104 SLE patients and 56 volunteers. RESULTS: The level of GRα mRNA was lower in the SLE group (the relative level was 1.24±0.97)than in the control group (the relative level was 2.31±1.42, P<0.05), and the level of GRß mRNA was higher in the SLE group(the relative level was 0.61±1.23) than in the control group(the relative level was 0.18±0.21, P<0.05). The level of GRα was lower in the active group (the relative level was 0.68±0.40) than in the inactive group(the relative level was 1.65±1.06, P<0.01), but the level of GRß was higher in the active group(the relative level was 0.88±1.56) than in the inactive group(the relative level was 0.24±0.23, P<0.01); GRα mRNA was related negatively to the SLEDAI score and dsDNA, but GRß mRNA was related positively to the SLEDAI score and dsDNA(P<0.01).The level of GRα mRNA was lower in the dsDNA positive group(the relative level was 0.89±0.66) than in the dsDNA negative group (the level was 1.54±1.10), the level of GRß mRNA was higher in the dsDNA positive group (the relative level was 0.95±1.60) than in the dsDNA negative group (the relative level was 0.22±0.21). The level of GRß mRNA and the value of GRß mRNA/ GRα mRNA was obviously higher in the SLE group with cardiac involvement (the relative level was 1.02 ±1.76, the valve of GRß / GRα was 1.10±2.02)than in the SLE group without cardiac involvement (the relative level was 0.28±0.31, the valve of GRß / GRα was 0.32±0.32, P<0.05), and the level of GRα mRNA wasn't significant in the two groups (P>0.05). CONCLUSION: The levels of GRα mRNA and GRß mRNA maybe play an important role in the pathogenesis of SLE. And the levels of GRα mRNA and GRß mRNA are related to the activity of SLE. The level of GRß mRNA and the value of GRß mRNA/ GRα mRNA are related with cardiovascular involvement in SLE.

Hexa-kis-(µ2-4-amino-3,5-dimethyl-4H-1,2,4-triazole)hexa-aqua-tricobalt(II) naphthalene-1,5-disulfonate tetra-chloride.

In the centrosymmetric trinuclear cation of the title compound, [Co3(C4H(8)N4)6(H2O)6](C10H6O6S2)Cl4, the three Co(II) atoms are bridged by six triazole mol-ecules via the N atoms in the 1,2-positions. The central Co(II) atom, lying on an inversion center, is coordinated by six triazole N atoms while the terminal Co(II) atoms are coordinated by three triazole N atoms and three water O atoms in a distorted octa-hedral geometry. The naphthalene-disulfonate anion is also centrosymmetric. The four chloride counter anions are half-occupied; the H atoms of the amino groups show an occupancy of 2/3. O-H⋯Cl, O-H⋯O and N-H⋯O hydrogen bonds link the complex cations and the chloride and naphthalene-1,5-disulfonate anions.

[Structure dynamics of communities after cutting Phyllostachys edulis along altitude in Mount Tianmu, China.] / 天目山不同海拔毛竹伐除区群落结构变化.

We examined the dynamics of community structure in forests formed after cutting all Phyllostachys edulis at altitude of 480, 580, 700 and 800 m of the Mount Tianmu National Nature Reserve in Zhejiang Province, from 2017 to 2020, using phytocommunity method. Results showed that the total number of plant individuals was 515 belonging to 50 species, 43 genera and 27 families in 2017. After three years, 30 new plant species emerged, belonging to 23 genera and 14 families, and the number of individuals increased by 116.9% in 2020. The new species were mainly P. edulis, Callicarpa bodinieri, Lindera glauca, Litsea cubeba and Broussonetia papyrifera, which primarily distributed at the altitude of 580 and 700 m. The tree species with the largest importance value in the communities at altitude of 580, 700 and 800 m remained stable, including Cunninghamia lanceolata, Ailanthus altis-sima and Liquidambar formosana, whereas that in community at altitude of 480 m changed from C. lanceolata to Camellia oleifera. Meanwhile, the diameter distributions of community significantly differed across different altitudes. The diameter distribution of the community at altitude of 480 m displayed a single peak left skewness from the reverse 'J' type, whilst that at altitude of 700 m developed from a reverse 'J' type to an exponential type. The diameter distribution in the community at altitude of 800 m followed a normal pattern and the peak value shifted from 24 to 30 cm. Both the Simpson dominance index and Shannon diversity index of the four communities increased across the three years, and all decreased significantly with the increase of altitude. Meanwhile, ß diversity increased with rising altitude and increasing distance among altitudes. The recruitment of new species in 2020 provided sufficient seedlings and saplings for natural regeneration, but it had not yet succeeded to the subtropical climax community.