It is vital to understand the oxygen reduction reaction (ORR) mechanism at the molecular level for the rational design and synthesis of high activity fuel‐cell catalysts. Surface enhanced Raman ...spectroscopy (SERS) is a powerful technique capable of detecting the bond vibrations of surface species in the low wavenumber range, however, using it to probe practical nanocatalysts remains extremely challenging. Herein, shell‐isolated nanoparticle‐enhanced Raman spectroscopy (SHINERS) was used to investigate ORR processes on the surface of bimetallic Pt3Co nanocatalyst structures. Direct spectroscopic evidence of *OOH suggests that ORR undergoes an associative mechanism on Pt3Co in both acidic and basic environments. Density functional theory (DFT) calculations show that the weak *O adsorption arise from electronic effect on the Pt3Co surface accounts for enhanced ORR activity. This work shows SHINERS is a promising technique for the real‐time observation of catalytic processes.
SHINERS (shell‐isolated nanoparticle enhanced Raman spectroscopy) was used to reveal in situ the oxygen reduction reaction (ORR) process on Pt3Co nanocatalysts. An associative mechanism was proposed for ORR on nanocatalysts and the weaker *O adsorption lead to the improved activity.
α-Synucleinopathies are characterized by autonomic dysfunction and motor impairments. In the pure autonomic failure (PAF), α-synuclein (α-Syn) pathology is confined within the autonomic nervous ...system with no motor features, but mouse models recapitulating PAF without motor dysfunction are lacking. Here, we show that in TgM83
mice, inoculation of α-Syn preformed fibrils (PFFs) into the stellate and celiac ganglia induces spreading of α-Syn pathology only through the autonomic pathway to both the central nervous system (CNS) and the autonomic innervation of peripheral organs bidirectionally. In parallel, the mice develop autonomic dysfunction, featured by orthostatic hypotension, constipation, hypohidrosis and hyposmia, without motor dysfunction. Thus, we have generated a mouse model of pure autonomic dysfunction caused by α-Syn pathology. This model may help define the mechanistic link between transmission of pathological α-Syn and the cardinal features of autonomic dysfunction in α-synucleinopathy.
Objective
Arthroscopic release is effective for patients with shoulder stiffness, but the traditional inside‐out procedure cannot effectively alleviate the mobility of some severe stiff shoulder and ...even cause itrogenic injuries sometimes. The aim of this study is to evaluate the clinical efficacy and advantages of a modified outside‐in shoulder release approach for severe shoulder stiffness.
Methods
Included in this retrospective study were 15 patients (five male and 10 female) with severe shoulder stiffness who underwent modified outside‐in shoulder release surgery at our hospital between June 2019 and March 2021. Of them, 10 patients had a primary frozen shoulder and five had secondary shoulder stiffness, involving the right shoulder in six cases and the left shoulder in nine cases. The mean age of the 15 patients was 56.7 (34–69) years. The patients were instructed to exercise passively from second‐day post‐operation and enhance the rehabilitation exercise gradually. All patients received a range of motion (ROM) examination before and after surgery. The American Shoulder and Elbow Surgeon's Score (ASES), Constant Score (CS), and Visual Analog Scale (VAS) score for pain were recorded. All data were tested by normal distribution first and then by paired T test, otherwise by Wilcoxon rank sum test.
Results
The mean follow‐up period was 18.2 (12–33) months. Compared with the preoperative value, the mean ASES score at the final follow‐up improved from 38.4 ± 7.37 to 88.13 ± 6.33 points; the mean CS score from 43.27 ± 6.71 to 78.74 ± 6.93 points; the mean VAS score from 5.07 ± 1.03 to 0.81 ± 0.83 points; forward flexion from 81.93° ± 11.45° to 156.73° ± 9.12°; abduction from 65.93° ± 16.82° to 144.80° ± 8.83°; neutral external rotation from 13.53° ± 10.38° to 51.20° ± 4.77°; internal rotation from the buttock to waist (L3), all showing a significant difference (P < 0.0001). No serious complication was observed in any patient during the postoperative follow‐up periods.
Conclusion
The present study has demonstrated that the modified arthroscopic outside‐in shoulder release approach can improve ROM of patients and alleviate pain effectively, proving it to be an appropriate surgical option for the treatment of severe shoulder stiffness.
A modified arthroscopic outside‐in release approach can improve the range of motion and quality of patients with severe shoulder stiffness, making it an appropriate surgical option for the treatment of severe shoulder stiffness.
The Gram-negative bacterium Xanthomonas oryzae pv. oryzicola (Xoc) is the causal agent of rice bacterial leaf streak (BLS), one of the most destructive diseases of rice (Oryza sativa L.) that is the ...important staple crop. Xoc can invade host leaves via stomata and wounds and its type three secretion system (T3SS) is pivotal to its pathogenic lifestyle. In this study, using a novel dual RNA-seq approach, we examined transcriptomes of rice and Xoc in samples inoculated with wild type Xoc GX01 and its T3SS defective strain (T3SD), to investigate the global transcriptional changes in both organisms. Compared with T3SD strain, rice inoculated with wild type Xoc GX01 resulted in significant expression changes of a series of plant defence related genes, including ones altered in plant signalling pathway, and downregulated in phenylalanine metabolism, flavonoid and momilactone biosynthesis, suggesting repression of plant defence response and reduction in both callose deposition and phytoalexin accumulation. Also, some known transcription activator-like effector (TALE) targets were induced by Xoc GX01, e.g. OsSultr3;6 which contributes to rice susceptibility. Some cell elongation related genes, including several expansin genes, were induced by GX01 too, suggesting that Xoc may exploit this pathway to weaken cell wall strength, beneficial for bacterial infection. On the other hand, compared with wild type, the T3SD strain transcriptome in planta was characterized by downregulation of ATP, protein and polysaccharide synthesis, and upregulation of antioxidation and detoxification related genes, revealing that T3SD strain faced serious starvation and oxidation stresses in planta without a functional T3SS. In addition, comparative global transcript profiles of Xoc in planta and in medium revealed an upregulation of virulence factor synthesis and secretion in planta in favour of bacterial infection. Collectively, this study provides a comprehensive representation of cross talk between the host and bacterial pathogen, revealing insights into the Xoc-rice pathogenic dynamic and reveals novel strategies exploited by this important pathogen to cause disease.
Background Observational studies suggest that patients with immunoglobulin A nephropathy (IgAN) with active proliferative lesions show a good response to immunosuppressive treatment. Study Design ...Multicenter, prospective, randomized, controlled trial. Setting & Participants 176 patients with IgAN with active proliferative lesions (cellular and fibrocellular crescents, endocapillary hypercellularity, or necrosis), proteinuria with protein excretion ≥ 1.0 g/24 h, and estimated glomerular filtration rate > 30 mL/min/1.73 m2. Intervention Mycophenolate mofetil (MMF) group: MMF, 1.5 g/d, for 6 months and prednisone, 0.4 to 0.6 mg/kg/d, for 2 months and then tapered by 20% per month for the next 4 months; prednisone group: prednisone, 0.8 to 1.0 mg/kg/d, for 2 months and then tapered by 20% per month for the next 4 months. All patients were followed up for another 6 months. Outcomes The primary end point was complete remission rate at 6 and 12 months. Results At baseline, median estimated glomerular filtration rates were 90.2 and 94.3 mL/min/1.73 m2 and mean proteinuria was protein excretion of 2.37 and 2.47 g/24 h in the MMF and prednisone groups, respectively. At 6 months, complete remission rates were 37% (32 of 86 patients) and 38% (33 of 88 patients); the between-group difference was not statistically significant ( P = 0.9). At 12 months, complete remission rates were 48% (35 of 73 patients) and 53% (38 of 72 patients) in the MMF and prednisone groups, respectively; the between-group difference was not statistically significant ( P = 0.6). Incidences of Cushing syndrome and newly diagnosed diabetes mellitus were lower in the MMF group than in the prednisone group. Limitations Not all participants were treated with renin-angiotensin system blockers, relatively short follow-up. Conclusions MMF plus prednisone versus full-dose prednisone did not differ in reducing proteinuria, but patients treated with the former had fewer adverse events in patients with IgAN with active proliferative lesions.
Assisted reproductive technology (ART) is associated with an increased risk of adverse metabolic health in offspring, and these findings have been demonstrated in animal models without parental ...infertility issues. However, it is unclear what changes lead to abnormal metabolism. The activation of the renin-angiotensin system (RAS) has been related to various aspects of metabolic syndrome. Thus, we focused on the local RAS of the liver, which is the central organ for glucose and lipid metabolism in offspring conceived by in vitro fertilization (IVF), and studied the role of local liver RAS in metabolic diseases.
Male C57BL/6 mouse offspring obtained by natural pregnancy and IVF were fed a standard chow diet or a high-fat diet (HFD) from 4 weeks of age through 16 weeks of age. We assessed glucose and lipid metabolism, hepatic histopathology, and the gene and protein expression of key RAS components. In addition, the blocker losartan was used from 4 weeks of age through 16 weeks of age to investigate the regulatory mechanisms of abnormal local RAS on metabolic activity in the IVF offspring liver.
The growth trajectories of IVF offspring body and liver weights were different from those of naturally pregnant offspring. Impaired glucose tolerance (IGT) and insulin resistance (IR) occurred in IVF-conceived male offspring. After continuous HFD feeding, male offspring in the IVF group underwent earlier and more severe IR. Furthermore, there was a trend of lipid accumulation in the livers of chow-fed IVF offspring. Hepatic steatosis was also more serious in the IVF offspring after HFD treatment. Type 1 receptor (AT1R), which is the primary receptor mediating the action of angiotensin (Ang) II, has been confirmed to be upregulated in IVF offspring livers. Losartan reduced or even eliminated most of the significant differences between the IVF and NC groups after HFD consumption.
The upregulation of AT1R expression in the liver increased the activity of the local RAS, resulting in abnormal glucose and lipid metabolism and lipid accumulation in the liver, significantly increasing the risk of nonalcoholic fatty liver disease (NAFLD) in IVF offspring.
Summary
Molecules of the diffusible signal factor (DSF)‐family are a class of quorum sensing (QS) signals used by the phytopathogens Xanthomonas. Studies during the last decade have outlined how ...Xanthomonas cells enter the QS phase. However, information on the mechanism underlying its exit from the QS phase is limited. RpfB has recently been reported as a fatty acyl‐CoA ligase (FCL) that activates a wide range of fatty acids to their CoA esters in vitro. Here, we establish an improved quantification assay for DSF‐family signals using liquid chromatography‐mass spectrometry in X. campestris pv. campestris (Xcc). We first demonstrated that RpfB represents a naturally occurring DSF‐family signal turnover system. RpfB effectively turns over DSF‐family signals DSF and BDSF in vivo. RpfB FCL enzymatic activity is required for DSF and BDSF turnover. Deletion of rpfB slightly increased Xcc virulence in the Chinese radish and overexpression of rpfB significantly decreased virulence. We further showed that the expression of rpfB is growth phase‐dependent, and its expression is significantly enhanced when Xcc cells enter the stationary phase. DSF regulates rpfB expression in a concentration‐dependent manner. rpfB expression is also negatively regulated by the DSF signalling components RpfC, RpfG and Clp. The global transcription factor Clp directly binds to the AATGC‐tgctgc‐GCATC motif in the promoter region of rpfB to repress its expression. Finally, RpfB‐dependent signal turnover system was detected in a wide range of bacterial species, suggesting that it is a conserved mechanism.
13-15% of breast cancer/BC patients diagnosed as pathological complete response/pCR after neoadjuvant systemic therapy/NST suffer from recurrence. This study aims to estimate the rationality of ...organoid forming potential/OFP for more accurate evaluation of NST efficacy.
OFPs of post-NST residual disease/RD were checked and compared with clinical approaches to estimate the recurrence risk. The phenotypes of organoids were classified via HE staining and ER, PR, HER2, Ki67 and CD133 immuno-labeling. The active growing organoids were subjected to drug sensitivity tests.
Of 62 post-NST BC specimens, 24 were classified as OFP-I with long-term active organoid growth, 19 as OFP-II with stable organoid growth within 3 weeks, and 19 as OFP-III without organoid formation. Residual tumors were overall correlated with OFP grades (P < 0.001), while 3 of the 18 patients (16.67%) pathologically diagnosed as tumor-free (ypT0N0M0) showed tumor derived-organoid formation. The disease-free survival/DFS of OFP-I cases was worse than other two groups (Log-rank P < 0.05). Organoids of OFP-I/-II groups well maintained the biological features of their parental tumors and were resistant to the drugs used in NST.
The OFP would be a complementary parameter to improve the evaluation accuracy of NST efficacy of breast cancers.
pv. campestris is the causative agent of black rot disease in crucifer plants. This Gram-negative bacterium utilizes the type III secretion system (T3SS), encoded by the
gene cluster, to aid in its ...resistance to host defenses and the ability to cause disease. The T3SS injects a set of proteins known as effectors into host cells that come into contact with the bacterium. The T3SS is essential for the virulence and hypersensitive response (HR) of
pv. campestris, making it a potential target for disease control strategies. Using a unique and straightforward high-throughput screening method, we examined a large collection of diverse small molecules for their potential to modulate the T3SS without affecting the growth of
pv. campestris. Screening of 13,129 different compounds identified 10 small molecules that had a significant inhibitory influence on T3SS. Moreover, reverse transcription-quantitative PCR (qRT-PCR) assays demonstrated that all 10 compounds repress the expression of the
genes. Interestingly, the effect of these small molecules on
genes may be through the HpaS and ColS sensor kinase proteins that are key to the regulation of the T3SS
Five of the compounds were also capable of inhibiting
pv. campestris virulence in a Chinese radish leaf-clipping assay. Furthermore, seven of the small molecules significantly weakened the HR in nonhost pepper plants challenged with
pv. campestris. Taken together, these small molecules may provide potential tool compounds for the further development of antivirulence agents that could be used in disease control of the plant pathogen
pv. campestris.
The bacterium
pv. campestris is known to cause black rot disease in many socioeconomically important vegetable crops worldwide. The management and control of black rot disease have been tackled with chemical and host resistance methods with variable success. This has motivated the development of alternative methods for preventing this disease. Here, we identify a set of novel small molecules capable of inhibiting
pv. campestris virulence, which may represent leading compounds for the further development of antivirulence agents that could be used in the control of black rot disease.
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