First report of root rot in Trichosanthes kirilowii (Chinese cucumber) caused by Fusarium sulawesiense in China.

Trichosanthes kirilowii (Chinese cucumber) is one of the important perennial herbaceous vines in China, with putative pharmacological activities including anti-tumor and lowering blood lipids. In July 2022, T. kirilowii plants with brownish roots and chlorotic leaves were observed in several orchards in Qianshan, Anhui province, China (30°34'N, 116° 30'E). The disease incidence reached approximately 10% within an area spanning 20 ha, and was higher in poorly drained orchards. To investigate this root rot disease, five symptomatic plants were collected from the diseased orchards in Qianshan. Subsequently, small sections of the diseased roots were surface sterilized using 1% sodium hypochlorite and 75% ethanol for 45 seconds each. Then, sterilized roots were placed onto PDA (20% diced potato, 2% glucose, and 1.5% agar, and distilled water) and incubated at 28℃ in the dark for 6 days. A total of eight isolates with similar morphology were obtained and purified by single spore culturing. Two representative isolates (QSJ4 and QSJ5) were chosen for further analysis. When grown on PDA, the surface of each colony was white with dense aerial mycelium and pale orange color in the center with a white edge on the reverse side. Macroconidia produced on carnation leaf agar plates were falcate, slightly curved, and 3 to 5 septate, with papillate apical cells and indistinct basal cells. Macroconidia were 17.4-42.3 × 2.4-5.8 µm (n = 100). Microconidia were ellipsoidal in shape, slightly curved or not curved, and most were 1-septate, 9.6-16.7 × 1.5-3.8 µm (n = 40). The identity was determined by sequencing four loci (i. e., ITS, CAL, EF1-α and RPB2) from two representative isolates (Liu et al. 1999; O'Donnell et al. 1998, 2000; Reeb et al. 2004; White et al. 1990). Sequences were deposited in GenBank [ITS (OR267397, OR267398), CAL (OR296634, OR296635), EF1-α (OR296637, OR296638) and RPB2 (OR296640, OR296641)]. A phylogenetic analysis was performed with three loci (CAL, EF1-α, RPB2) comprising a concatenated dataset of 68 strains in the Fusarium incarnatum-equiseti species complex (Han et al., 2023). The results showed that isolates QSJ4 and QSJ5 clustered closely together with reference strains of F. sulawesiense. Pathogenicity tests were conducted by inoculating three-week-old healthy T. kirilowii seedings (cv. Wanlou No. 9) cultivated in substrate soil in pots with a diameter of 17 cm and a height of 10.5 cm. A 20 mL aliquot of spore suspension (106 conidia/mL) of F. sulawesiense was inoculated to the roots of potted seedlings by irrigation. Each strain was inoculated onto three seedlings. The potted seedlings were inoculated with sterile water as the negative control. Inoculated seedlings were incubated in a growth chamber at 25℃ and 75% relative humidity. After one week, typical symptoms of root necrosis and leaf chlorosis were observed on the inoculated seedlings. Disease symptoms were not observed on the control seedlings. All seedlings showing root necrosis and leaf chlorosis caused by the inoculations were subjected to fungal isolation, and the results showed that the reisolated colonies matched the inoculated ones for morphologies and ITS sequences. Fusarium sulawesiense has been previously reported to cause disease on Cucumis melo L. in Brazil (Medeiros Araujo et al. 2021), Musa acuminata Colla in south Sulawesi (Maryani et al. 2019), Luffa aegyptiaca Miller and Musa nana Lour. in China (Wang et al. 2019). To our knowledge, this is the first report of F. sulawesiense causing Fusarium root rot of T. kirilowii in China.

Biallelic missense variants in COG3 cause a congenital disorder of glycosylation with impairment of retrograde vesicular trafficking.

Biallelic variants in genes for seven out of eight subunits of the conserved oligomeric Golgi complex (COG) are known to cause recessive congenital disorders of glycosylation (CDG) with variable clinical manifestations. COG3 encodes a constituent subunit of the COG complex that has not been associated with disease traits in humans. Herein, we report two COG3 homozygous missense variants in four individuals from two unrelated consanguineous families that co-segregated with COG3-CDG presentations. Clinical phenotypes of affected individuals include global developmental delay, severe intellectual disability, microcephaly, epilepsy, facial dysmorphism, and variable neurological findings. Biochemical analysis of serum transferrin from one family showed the loss of a single sialic acid. Western blotting on patient-derived fibroblasts revealed reduced COG3 and COG4. Further experiments showed delayed retrograde vesicular recycling in patient cells. This report adds to the knowledge of the COG-CDG network by providing collective evidence for a COG3-CDG rare disease trait and implicating a likely pathology of the disorder as the perturbation of Golgi trafficking.

Time-Resolved Extensional Rheo-NMR Spectroscopy for Investigating Polymer Nanocomposites under Deformation.

Understanding the microstructure change of polymer nanocomposites (PNCs) under elongation deformation at the molecular level is the key to coupling structure-property relationships of PNCs. In this study, we developed our recently proposed in situ extensional rheology NMR device, Rheo-spin NMR, which can simultaneously obtain both the macroscopic stress-strain curves and the microscopic molecular information with the total sample weight of ∼6 mg. This enables us to conduct a detailed investigation of the evolution of the interfacial layer and polymer matrix in nonlinear elongational strain softening behaviors. A quantitative method is established for in situ analysis of (1) the fraction of the interfacial layer and (2) the network strand orientation distribution of the polymer matrix based on the molecular stress function model under active deformation. The results show that for the current highly filled silicone nanocomposite system, the influence of the interfacial layer fraction on mechanical property change during small amplitude deformation is quite minor, while the main role is reflected in rubber network strand reorientation. The Rheo-spin NMR device and the established analysis method are expected to facilitate the understanding of the reinforcement mechanism of PNC, which can be further applied to understand the deformation mechanism of other systems, i.e., glassy and semicrystalline polymers and the vascular tissues.

Biomimetic human eyes in adaptive lenses with conductive gels.

To investigate the imaging effect, adaptive robust lenses are prepared by sealing transparent liquid or gel. Lenses are fabricated using the negative-pressure method, which is a benefit for a stable biconvex shape. Under the action of an electric field, the soft lens deforms following the dielectric elastomer actuator (DEA). DE (dielectric elastomer) membranes expand in the plane perpendicular to the electric field lines. The toroidal driving area leads to a decrease in lens diameter and an increase in convex curvature. Therefore, the focal length of the lens becomes shorter. The experimental measurement utilizes the double focal length method. As a result, the largest focal length change that could be achieved was 44.7% (190 mm→105 mm) of the soft lens using a DEA with carbon grease electrodes. Furthermore, the ECG (electrocardiogram) conductive gel could replace traditional carbon grease for DEA electrodes in optics. This type of transparent electrode is creatively applied to a biomedical lens. Under the same conditions, the electrostriction rate in a DEA with ECG gel was achieved at 33%, which was greater than that of 28% in a DEA coupled with carbon grease electrode. Adaptive lenses have characteristics such as easy fabrication, low cost, and strong operability, and they possess great potential application value in biomedical feild.

Efficacy and safety of Paxlovid in severe adult patients with SARS-Cov-2 infection: a multicenter randomized controlled study.

Background: Nirmatrelvir plus ritonavir (Paxlovid) reduced the risk of hospitalization or death by 89% in high-risk, ambulatory adults with COVID-19. We aimed at studying the efficacy and safety of Paxlovid in hospitalized adult patients with SARS-Cov-2 (Omicron BA.2.2 variant) infection and severe comorbidities. Methods: We conducted an open-label, multicenter, randomized controlled trial in which hospitalized adult patients with severe comorbidities were eligible and assigned in a 1:1 ratio to receive either 300 mg of nirmatrelvir plus 100 mg of ritonavir every 12 h for 5 days with standard treatment or only standard treatment. All-cause mortality on day 28, the duration of SARS-CoV-2 RNA clearance, and safety were evaluated. Findings: 264 patients (mean age, 70.35 years; 122 [46.21%] female) who met the criteria were enrolled at 5 sites in Shanghai from April 10 to May 19 in 2022. After randomization, a total of 132 patients were assigned to receive Paxlovid treatment plus standard treatment, and 132 patients were assigned to receive only standard treatment. The overall 28-day mortality was 4.92%, 8 patients died in the standard treatment group and 5 died in the Paxlovid plus standard treatment group. There was no significant difference in mortality from any cause at 28 days between the Paxlovid plus standard treatment group and the standard treatment group (absolute risk difference [ARD], 2.27; 95% CI -2.94 to 7.49, P = 0.39). There was no significant difference in the duration of SARS-CoV-2 RNA clearance among the two groups (mean days, 10 in Paxlovid plus standard treatment group and 10.50 in the standard treatment group; ARD, -0.62; 95% CI -2.29 to 1.05, P = 0.42). The incidence of adverse events that occurred during the treatment period was similar in the two groups (any adverse event, 10.61% with Paxlovid plus standard treatment vs. 7.58% with the standard, P = 0.39; serious adverse events, 4.55% vs. 3.788%, P = 0.76). Interpretation: Paxlovid showed no significant reduction in the risk of all-cause mortality on day 28 and the duration of SARS-CoV-2 RNA clearance in hospitalized adult COVID-19 patients with severe comorbidities. Funding: National Natural Science Foundation of China (grant number: 82172152, 81873944).

The Swedish COG6-CDG experience and a comprehensive literature review.

Here, we present the first two Swedish cases of Conserved Oligomeric Golgi complex subunit 6-congenital disorders of glycosylation (COG6-CDG). Their clinical symptoms include intellectual disability, Attention Deficit/Hyperactivity Disorder (ADHD), delayed brain myelinization, progressive microcephaly, joint laxity, hyperkeratosis, frequent infections, and enamel hypoplasia. In one family, compound heterozygous variants in COG6 were identified, where one (c.785A>G; p.Tyr262Cys) has previously been described in patients of Moroccan descent, whereas the other (c.238G>A; p.Glu80Lys) is undescribed. On the other hand, a previously undescribed homozygous duplication (c.1793_1795dup) was deemed the cause of the disease. To confirm the pathogenicity of the variants, we treated patient and control fibroblasts with the ER-Golgi transport inhibitor Brefeldin-A and show that patient cells manifest a significantly slower anterograde and retrograde ER-Golgi transport.

GLUT1 is a highly efficient L-fucose transporter.

Understanding L-fucose metabolism is important because it is used as a therapy for several congenital disorders of glycosylation. Exogenous L-fucose can be activated and incorporated directly into multiple N- and O-glycans via the fucose salvage/recycling pathway. However, unlike for other monosaccharides, no mammalian L-fucose transporter has been identified. Here, we functionally screened nearly 140 annotated transporters and identified GLUT1 (SLC2A1) as an L-fucose transporter. We confirmed this assignment using multiple approaches to alter GLUT1 function, including chemical inhibition, siRNA knockdown, and gene KO. Collectively, all methods demonstrate that GLUT1 contributes significantly to L-fucose uptake and its utilization at low micromolar levels. Surprisingly, millimolar levels of D-glucose do not compete with L-fucose uptake. We also show macropinocytosis, but not other endocytic pathways, can contribute to L-fucose uptake and utilization. In conclusion, we determined that GLUT1 functions as the previously missing transporter component in mammalian L-fucose metabolism.

COG4 mutation in Saul-Wilson syndrome selectively affects secretion of proteins involved in chondrogenesis in chondrocyte-like cells.

Saul-Wilson syndrome is a rare skeletal dysplasia caused by a heterozygous mutation in COG4 (p.G516R). Our previous study showed that this mutation affected glycosylation of proteoglycans and disturbed chondrocyte elongation and intercalation in zebrafish embryos expressing the COG4p.G516R variant. How this mutation causes chondrocyte deficiencies remain unsolved. To analyze a disease-relevant cell type, COG4p.G516R variant was generated by CRISPR knock-in technique in the chondrosarcoma cell line SW1353 to study chondrocyte differentiation and protein secretion. COG4p.G516R cells display impaired protein trafficking and altered COG complex size, similar to SWS-derived fibroblasts. Both SW1353 and HEK293T cells carrying COG4p.G516R showed very modest, cell-type dependent changes in N-glycans. Using 3D culture methods, we found that cells carrying the COG4p.G516R variant made smaller spheroids and had increased apoptosis, indicating impaired in vitro chondrogenesis. Adding WT cells or their conditioned medium reduced cell death and increased spheroid sizes of COG4p.G516R mutant cells, suggesting a deficiency in secreted matrix components. Mass spectrometry-based secretome analysis showed selectively impaired protein secretion, including MMP13 and IGFBP7 which are involved in chondrogenesis and osteogenesis. We verified reduced expression of chondrogenic differentiation markers, MMP13 and COL10A1 and delayed response to BMP2 in COG4p.G516R mutant cells. Collectively, our results show that the Saul-Wilson syndrome COG4p.G516R variant selectively affects the secretion of multiple proteins, especially in chondrocyte-like cells which could further cause pleiotropic defects including hampering long bone growth in SWS individuals.

Origin of cytoplasmic GDP-fucose determines its contribution to glycosylation reactions.

Biosynthesis of macromolecules requires precursors such as sugars or amino acids, originating from exogenous/dietary sources, reutilization/salvage of degraded molecules, or de novo synthesis. Since these sources are assumed to contribute to one homogenous pool, their individual contributions are often overlooked. Protein glycosylation uses monosaccharides from all the above sources to produce nucleotide sugars required to assemble hundreds of distinct glycans. Here, we demonstrate that cells identify the origin/heritage of the monosaccharide, fucose, for glycosylation. We measured the contribution of GDP-fucose from each of these sources for glycan synthesis and found that different fucosyltransferases, individual glycoproteins, and linkage-specific fucose residues identify and select different GDP-fucose pools dependent on their heritage. This supports the hypothesis that GDP-fucose exists in multiple, distinct pools, not as a single homogenous pool. The selection is tightly regulated since the overall pool size remains constant. We present novel perspectives on monosaccharide metabolism, which may have a general applicability.

A cryo-bulge apparatus for in situ weather balloon crystallization capturing during blowing by synchrotron radiation x-ray scattering.

A cryo-bulge apparatus, which can be directly installed in the synchrotron radiation x-ray scattering beamline, is designed and manufactured. Using the cryo-bulge apparatus, the crystallization of natural rubber during blowing can be captured in situ. For mechanical measurements, the rubber film is tightly clamped at the periphery of a circular window. A low temperature measurement is achieved by the presence of a large iron block, which ensures low temperature variation (<±2 °C in 1 h) during x-ray data acquisition. Since the incident x-ray beam passes through the top-most position of the rubber film, the information obtained by the current equipment is essentially under an equibiaxial deformation mode. Owing to precisely controlled internal pressure and temperature, the crystallization of rubber can be observed in situ by wide-angle x-ray scattering. The onset of crystallization is observed at a temperature T < 0 °C with an internal pressure P > 21 kPa. This suggests that the crystallization of rubber during blowing can occur under the equibiaxial deformation condition at low temperatures. The power scaling law is found to be 0.52%/kPa. The cryo-bulge apparatus is capable of clarifying the microstructural evolution of rubber during multi-dimensional deformation, which can provide guidance for the optimization of a weather balloon.

Self-Attention-Augmented Generative Adversarial Networks for Data-Driven Modeling of Nanoscale Coating Manufacturing.

Nanoscale coating manufacturing (NCM) process modeling is an important way to monitor and modulate coating quality. The multivariable prediction of coated film and the data augmentation of the NCM process are two common issues in smart factories. However, there has not been an artificial intelligence model to solve these two problems simultaneously. Focusing on the two problems, a novel auxiliary regression using a self-attention-augmented generative adversarial network (AR-SAGAN) is proposed in this paper. This model deals with the problem of NCM process modeling with three steps. First, the AR-SAGAN structure was established and composed of a generator, feature extractor, discriminator, and regressor. Second, the nanoscale coating quality was estimated by putting online control parameters into the feature extractor and regressor. Third, the control parameters in the recipes were generated using preset parameters and target quality. Finally, the proposed method was verified by the experiments of a solar cell antireflection coating dataset, the results of which showed that our method performs excellently for both multivariable quality prediction and data augmentation. The mean squared error of the predicted thickness was about 1.6~2.1 nm, which is lower than other traditional methods.

Practice and Evaluation of a Protocol for Collating Information Related to the Emergency Clinical Pathway for Patients With Acute ST-Segment Elevation Myocardial Infarction.

Acute ST elevation myocardial infarction (STEMI) is a common acute and critical disease that requires rapid treatment within a limited window of time. In this study, we attempt to introduce a clinical pathway for the whole-process management of emergency STEMI based on the creation of a specific information system that matches the characteristics of emergency clinical work and evaluates their clinical value by quality control analysis. We deployed this system for 3 years and found that complications, heart failure, and medical costs during hospitalization were significantly reduced (p = 0.019) in patients with STEMI. By analyzing each link in the clinical pathway, our research indicates the clear clinical importance of developing methods to continuously improve data quality. Collectively, out research led to the optimization of an information system that will facilitate the clinical management of patients with STEMI.

An in situ stretching instrument combined with low field nuclear magnetic resonance (NMR): Rheo-Spin NMR.

An in situ stretching instrument combined with low field nuclear magnetic resonance (LF-NMR) was designed and developed, namely, Rheo-Spin NMR. The time resolved stress-strain curve together with the corresponding NMR signal can be simultaneously obtained. The Rheo-Spin NMR contains the functional modules, including (1) the in situ stretching module, (2) the NMR signal acquisition module, and (3) the cavity of the NMR positioning module. The unique ring-like shape of the sample is used to replace the traditional dumbbell sample due to limited space in the NMR probe, and the whole ring-like sample will be deformed during the uniaxial stretching process, which avoids the generation of interference signals from the undeformed sample. The designed stretching assembly made by zirconia ceramics is manufactured to match and stretch the ring-like samples. The strain rate can be tuned within the range of 10-5-10-2 s-1 with the maximum stretching ratio λmax of ∼3.8. The in situ stretching experiments combined with LF-NMR were carried out successfully with natural rubber of different fractions of carbon black. The time-resolved T2 relaxometry was adopted to evaluate segmental relaxation during uniaxial deformation which, for the first time, provides the direct and in situ molecular dynamics information. The Rheo-Spin NMR is promising to provide more in-depth insights into the structure and dynamics evolution of polymer products under real service conditions.

Artificial Intelligence of Manufacturing Robotics Health Monitoring System by Semantic Modeling.

Robotics is widely used in nearly all sorts of manufacturing. Steady performance and accurate movement of robotics are vital in quality control. Along with the coming of the Industry 4.0 era, oceans of sensor data from robotics are available, within which the health condition and faults are enclosed. Considering the growing complexity of the manufacturing system, an automatic and intelligent health-monitoring system is required to detect abnormalities of robotics in real-time to promote quality and reduce safety risks. Therefore, in this study, we designed a novel semantic-based modeling method for multistage robotic systems. Experiments show that sole modeling is not sufficient for multiple stages. We propose a descriptor to conclude the stages of robotic systems by learning from operational data. The descriptors are akin to a vocabulary of the systems; hence, semantic checking can be carried out to monitor the correctness of operations. Furthermore, the stage classification and its semantics were used to apply various regression models to each stage to monitor the quality of each operation. The proposed method was applied to a photovoltaic manufacturing system. Benchmarks on production datasets from actual factories show the effectiveness of the proposed method to realize an AI-enabled real-time health-monitoring system of robotics.

Spectrum Analysis Enabled Periodic Feature Reconstruction Based Automatic Defect Detection System for Electroluminescence Images of Photovoltaic Modules.

Electroluminescence (EL) imaging is a widely adopted method in quality assurance of the photovoltaic (PV) manufacturing industry. With the growing demand for high-quality PV products, automatic inspection methods based on machine vision have become an emerging area concern to replace manual inspectors. Therefore, this paper presents an automatic defect-inspection method for multi-cell monocrystalline PV modules with EL images. A processing routine is designed to extract the defect features of the PV module, eliminating the influence of the intrinsic structural features. Spectrum domain analysis is applied to effectively reconstruct an improved PV layout from a defective one by spectrum filtering in a certain direction. The reconstructed image is used to segment the PV module into cells and slices. Based on the segmentation, defect detection is carried out on individual cells or slices to detect cracks, breaks, and speckles. Robust performance has been achieved from experiments on many samples with varying illumination conditions and defect shapes/sizes, which shows the proposed method can efficiently distinguish intrinsic structural features from the defect features, enabling precise and speedy defect detections on multi-cell PV modules.

A practical scoring model to predict the occurrence of critical illness in hospitalized patients with SARS-CoV-2 omicron infection.

Background: The variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged repeatedly, especially the Omicron strain which is extremely infectious, so early identification of patients who may develop critical illness will aid in delivering proper treatment and optimizing use of resources. We aimed to develop and validate a practical scoring model at hospital admission for predicting which patients with Omicron infection will develop critical illness. Methods: A total of 2,459 patients with Omicron infection were enrolled in this retrospective study. Univariate and multivariate logistic regression analysis were performed to evaluate predictors associated with critical illness. Moreover, the area under the receiver operating characteristic curve (AUROC), continuous net reclassification improvement, and integrated discrimination index were assessed. Results: The derivation cohort included 1721 patients and the validation cohort included 738 patients. A total of 98 patients developed critical illness. Thirteen variables were independent predictive factors and were included in the risk score: age > 65, C-reactive protein > 10 mg/L, lactate dehydrogenase > 250 U/L, lymphocyte < 0.8*10^9/L, white blood cell > 10*10^9/L, Oxygen saturation < 90%, malignancy, chronic kidney disease, chronic cardiac disease, chronic obstructive pulmonary disease, diabetes, cerebrovascular disease, and non-vaccination. AUROC in the derivation cohort and validation cohort were 0.926 (95% CI, 0.903-0.948) and 0.907 (95% CI, 0.860-0.955), respectively. Moreover, the critical illness risk scoring model had the highest AUROC compared with CURB-65, sequential organ failure assessment (SOFA) and 4C mortality scores, and always obtained more net benefit. Conclusion: The risk scoring model based on the characteristics of patients at the time of admission to the hospital may help medical practitioners to identify critically ill patients and take prompt measures.

Clinical Value of the Lactate/Albumin Ratio and Lactate/Albumin Ratio × Age Score in the Assessment of Prognosis in Patients With Sepsis.

Objective: To examine the clinical significance of the blood lactate (Lac)/serum albumin (Alb) ratio and the Lac/Alb × age score for assessing the severity and prognosis of patients with sepsis. Methods: A total of 8,029 patients with sepsis, aged >18 years were enrolled between June 2001 to October 2012 from the latest version of the Medical Information Mart for Intensive Care III (MIMIC-III v.1.4). The general data of the patients were obtained from hospital records and included gender, age, body mass index (BMI), laboratory indices, the sequential organ failure assessment (SOFA) score, and simplified acute physiology score II (SAPS II). The patients were graded and scored according to their age and then divided into a survival or death group based on their prognosis. The Lac/Alb ratio after ICU admission was calculated and compared between the two groups. The risk factors for death in patients with sepsis were determined using multivariate logistic regression analysis, while mortality was examined using receiver operating characteristic (ROC) curve and survival curve plots. Finally, the values of the Lac/Alb ratio and Lac/Alb × age score for assessing prognosis of patients with sepsis were analyzed and compared. Results: After items with default values were excluded, a total of 4,555 patients with sepsis were enrolled (2,526 males and 2,029 females). 2,843 cases were classified as the death group and 1,712 cases in the survival group. (1) The mean age, BMI, SOFA and SAPS II scores were higher in the death group than those in the survival group. Significant differences in baseline data between the two groups were also observed. (2) The patients in the death group were divided further into four subgroups according to the quartile of the Lac/Alb ratio from low to high. Comparison of the four subgroups showed that the death rate rose with an increase in the Lac/Alb ratio, while analysis of the survival curve revealed that patients with a higher Lac/Alb ratio had a worse prognosis. (3) Multivariate logistic regression analysis showed that age ≥ 60 years, overweight (BMI ≥ 24 kg/m2), Lac/Alb ratio ≥ 0.16, SOFA score ≥ 2 points, and SAPS II ≥ 40 points were independent risk factors for death in patients with septic. (4) ROC curve analysis indicated that the SAPS II, Lac/Alb x age score, SOFA, and Lac/Alb ratio were the best predictors of death in patients with sepsis. The Lac/Alb × age score was characterized by its simple acquisition and ability to quickly analyze the prognosis of patients. Conclusion: (1)A high Lac/Alb ratio is an independent risk factor for death in patients with sepsis. (2) Although the prognosis of sepsis can be accurately and comprehensively assessed by multi-dimensional analysis of multiple indices, the Lac/Alb × age score is more accurate and convenient for providing a general assessment of prognosis, so is worthy of further clinical recognition.

Protease-dependent defects in N-cadherin processing drive PMM2-CDG pathogenesis.

The genetic bases for the congenital disorders of glycosylation (CDG) continue to expand, but how glycosylation defects cause patient phenotypes remains largely unknown. Here, we combined developmental phenotyping and biochemical studies in a potentially new zebrafish model (pmm2sa10150) of PMM2-CDG to uncover a protease-mediated pathogenic mechanism relevant to craniofacial and motility phenotypes in mutant embryos. Mutant embryos had reduced phosphomannomutase activity and modest decreases in N-glycan occupancy as detected by matrix-assisted laser desorption ionization mass spectrometry imaging. Cellular analyses of cartilage defects in pmm2sa10150 embryos revealed a block in chondrogenesis that was associated with defective proteolytic processing, but seemingly normal N-glycosylation, of the cell adhesion molecule N-cadherin. The activities of the proconvertases and matrix metalloproteinases responsible for N-cadherin maturation were significantly altered in pmm2sa10150 mutant embryos. Importantly, pharmacologic and genetic manipulation of proconvertase activity restored matrix metalloproteinase activity, N-cadherin processing, and cartilage pathology in pmm2sa10150 embryos. Collectively, these studies demonstrate in CDG that targeted alterations in protease activity create a pathogenic cascade that affects the maturation of cell adhesion proteins critical for tissue development.

A case report of community-acquired Raoultella ornithinolytica infection in a healthy, young individual.

BACKGROUND: Raoultella ornithinolytica is a Gram-negative bacillus that resembles Klebsiella. This bacterium is present in many soil and aquatic environments and is a major causative agent of healthcare-associated infections (HAIs) in medical staff. Clinically, it has been reported to contribute to nosocomial infections in patients that include but are not limited to gastrointestinal, skin, and genitourinary tract infections. These complications are most common in hospitalized patients with underlying immunodeficiency, multiple comorbidities, or those receiving invasive surgery. CASE PRESENTATION: We present a case of a 25-year-old patient with a R. ornithinolytica infection. The patient had no history of any disease. Her main complaints were high fever, a scattered maculopapular rash, and superficial lymph node enlargement (SLNE). Peripheral blood samples were collected for high-throughput sequencing analysis to identify pathogenic microorganisms. The results confirmed a R. ornithinolytica infection, which was treated successfully using meropenem. Loratadine was also administered to treat the patient's compromised skin condition caused by an allergic reaction. CONCLUSIONS: To our knowledge, this is the first case of a systemic maculopapular rash and superficial lymphadenopathy caused by a R. ornithinolytica infection acquired at the community level. Based on this case, we recommend a combination of antibiotic and antiallergic drugs to treat a R. ornithinolytica infection and associated allergic reaction to the bacteria.