Clinical implication by differential analytical performances of serum free light chain quantitation analysis using fully automated analyzers.

OBJECTIVES: Free light chain (FLC) is used for the diagnosis and prediction with regard to the progression risk of plasma cell disorders and Freelite reagent using the SPAplus analyzer (The Binding Site) has been one of the widely used option. However, N Latex FLC reagent with the Atellica CH 930 analyzer (Siemens Healthineers) has shown the advantages of automation and high throughput. We aimed to evaluated clinical implication by differential analytical performances of two assays. METHODS: A total of 322 serum samples were collected from 193 patients requested for FLC analysis including 131 multiple myeloma patients. The precision, linearity, dilution recovery of N Latex FLC assay was evaluated. We compared the two assays and analyzed the monomer-dimer pattern for discrepant results. RESULTS: The precision, linearity, and dilution recovery performance was appropriate for the routine use in clinical laboratories. Despite the good correlation within normal range, proportional bias up-to 170% was observed in samples with high concentrations especially for lambda. The higher value samples with N Latex FLC assay contained more monomer forms than controls. All opposite changes of FLC burden by the N Latex FLC assay proved to present concordant dynamic changes when assessed by serum protein electrophoresis. CONCLUSIONS: Clinical laboratories should be aware of the inter-assay variability of FLC quantitative measurements using different platforms, especially for high concentrations of both kappa and lambda measurements, possibly due to monomer/dimer ratio diversity. Clinical interpretations for multiple myeloma disease status might not be dramatically affected only when the same assay is utilized during follow-up periods.

TMED3 Complex Mediates ER Stress-Associated Secretion of CFTR, Pendrin, and SARS-CoV-2 Spike.

Under ER stress conditions, the ER form of transmembrane proteins can reach the plasma membrane via a Golgi-independent unconventional protein secretion (UPS) pathway. However, the targeting mechanisms of membrane proteins for UPS are unknown. Here, this study reports that TMED proteins play a critical role in the ER stress-associated UPS of transmembrane proteins. The gene silencing results reveal that TMED2, TMED3, TMED9 and TMED10 are involved in the UPS of transmembrane proteins, such as CFTR, pendrin and SARS-CoV-2 Spike. Subsequent mechanistic analyses indicate that TMED3 recognizes the ER core-glycosylated protein cargos and that the heteromeric TMED2/3/9/10 complex mediates their UPS. Co-expression of all four TMEDs improves, while each single expression reduces, the UPS and ion transport function of trafficking-deficient ΔF508-CFTR and p.H723R-pendrin, which cause cystic fibrosis and Pendred syndrome, respectively. In contrast, TMED2/3/9/10 silencing reduces SARS-CoV-2 viral release. These results provide evidence for a common role of TMED3 and related TMEDs in the ER stress-associated, Golgi-independent secretion of transmembrane proteins.

The role of Jagged1 as a dynamic switch of cancer cell plasticity in PDAC assembloids.

Background: Pancreatic ductal adenocarcinoma (PDAC), which commonly relapses due to chemotherapy resistance, has a poor 5-year survival rate (< 10%). The ability of PDAC to dynamically switch between cancer-initiating cell (CIC) and non-CIC states, which is influenced by both internal and external events, has been suggested as a reason for the low drug efficacy. However, cancer cell plasticity using patient-derived PDAC organoids remains poorly understood. Methods: First, we successfully differentiated CICs, which were the main components of PDAC organoids, toward epithelial ductal carcinomas. We further established PDAC assembloids of organoid-derived differentiated ductal cancer cells with endothelial cells (ECs) and autologous immune cells. To investigate the mechanism for PDAC plasticity, we performed single-cell RNA sequencing analysis after culturing the assembloids for 7 days. Results: In the PDAC assembloids, the ECs and immune cells acted as tumor-supporting cells and induced plasticity in the differentiated ductal carcinomas. We also observed that the transcriptome dynamics during PDAC re-programming were related to the WNT/beta-catenin pathway and apoptotic process. Interestingly, we found that WNT5B in the ECs was highly expressed by trans interaction with a JAG1. Furthermore, JAG1 was highly expressed on PDAC during differentiation, and NOTCH1/NOTCH2 were expressed on the ECs at the same time. The WNT5B expression level correlated positively with those of JAG1, NOTCH1, and NOTCH2, and high JAG1 expression correlated with poor survival. Additionally, we experimentally demonstrated that neutralizing JAG1 inhibited cancer cell plasticity. Conclusions: Our results indicate that JAG1 on PDAC plays a critical role in cancer cell plasticity and maintenance of tumor heterogeneity.

A case of delivery of a pregnant woman with COVID-19 infection in Daegu, Korea.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is affiliated with the ß-coronavirus subgroup, which includes SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), but is far more infectious than the 2. Because it is potentially life-threatening to infants and pregnant women with weak immune systems, clinical manifestations and vertical transmission of COVID-19 are matters of interest. Staff of the obstetrics department of university hospitals in Daegu and of the Daegu metropolitan government designated Daegu Fatima Hospital for the delivery of pregnant women with suspected and confirmed SARS-CoV-2 infection. Thirteen pregnant women with laboratory-confirmed COVID-19 were identified. Among them was a 28-year-old pregnant woman who had recovered from COVID-19 and had given birth to a healthy girl at 38 weeks of gestational age. We present our uncommon experience with a brief review of literatures.

Emergency cesarean section performed in a patient with confirmed severe acute respiratory syndrome Coronavirus-2 -a case report.

BACKGROUND: Since the first case of severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) occurred in Wuhan in December 2019, the virus has spread globally. The World Health Organization declared the virus outbreak a pandemic on March 11, 2020. On January 19, 2020, a 35-year-old woman who returned from China was confirmed as the first SARS-CoV-2 infected case in Korea. Since then, it has spread all over Korea. CASE: We report the first case of a SARS-CoV-2 positive woman delivering a baby through cesarean section at 37+6 weeks of pregnancy in the Republic of Korea. CONCLUSIONS: This case suggested that negative pressure operating room, skillful medical team, and enhanced personal protective equipment including N95 masks, surgical cap, double gown, double gloves, shoe covers, and powered air-purifying respirator are required at the hospital for safe delivery in such a case.

IRE1α kinase-mediated unconventional protein secretion rescues misfolded CFTR and pendrin.

The most prevalent pathogenic mutations in the CFTR (ΔF508) and SLC26A4/pendrin (p.H723R), which cause cystic fibrosis and congenital hearing loss, respectively, evoke protein misfolding and subsequent defects in their cell surface trafficking. Here, we report that activation of the IRE1α kinase pathway can rescue the cell surface expression of ΔF508-CFTR and p.H723R-pendrin through a Golgi-independent unconventional protein secretion (UPS) route. In mammalian cells, inhibition of IRE1α kinase, but not inhibition of IRE1α endonuclease and the downstream effector XBP1, inhibited CFTR UPS. Treatment with the IRE1α kinase activator, (E)-2-(2-chlorostyryl)-3,5,6-trimethyl-pyrazine (CSTMP), rescued cell surface expression and functional activity of ΔF508-CFTR and p.H723R-pendrin. Treatment with a nontoxic dose of CSTMP to ΔF508-CFTR mice restored CFTR surface expression and CFTR-mediated anion transport in the mouse colon. These findings suggest that UPS activation via IRE1α kinase is a strategy to treat diseases caused by defective cell surface trafficking of membrane proteins, including ΔF508-CFTR and p.H723R-pendrin.

Ferrihydrite-impregnated granular activated carbon (FH@GAC) for efficient phosphorus removal from wastewater secondary effluent.

Adsorptive removal of phosphorus from wastewater effluents has attracted attention because of its reduced sludge production and potential P recovery. In this study, we investigated granular activated carbons (GACs) impregnated with amorphous ferrihydrite (FH@GAC) for the sorption of phosphorus from aqueous solutions. Preoxidation of intact GAC surfaces using an oxidant (e.g., hypochlorite) and strong acids (e.g., HNO3/H2SO4) was performed to create active functional groups (e.g., carboxyl or phenolic) for enhanced iron binding, leading to greater phosphorus uptake. Both the rate and the capacity of phosphorus sorption onto FH@GAC had significant, positive relationships (Pearson correlation coefficient r > 0.9) with the product of surface area and Fe content. The pseudo-second-order reaction kinetics explained the P sorption rate better than the pseudo-first-order reaction kinetics, whereas the Langmuir model fit the P sorption isotherm better than the Freundlich model. The iron content in the FH@GAC increased significantly (>10 mg/g) when GAC (e.g., BMC1050) was preoxidized by a 1:1 (w/w) concentrated HNO3/H2SO4 mixture. The Langmuir maximum P sorption capacity of a functionalized FH@BMC1050 adsorbent prepared with acid pretreatment was estimated to be substantial (5.73 mg P/g GAC corresponding to 526 mg P/g Fe). This sorption capacity was superior to that of a FH slurry, possibly because the nano-sized FH formed inside the GAC pores (<2.5 nm) can bind phosphate ions more effectively than FH aggregates. Fixed-bed column reactor operation with bicarbonate regeneration showed potential for efficient, continuous phosphorus removal by FH@GAC media.

Activated carbons impregnated with iron oxide nanoparticles for enhanced removal of bisphenol A and natural organic matter.

The removal of bisphenol A (BPA) is important for the provision of safe drinking water, but its removal in the presence of natural organic matter (NOM) is challenging. Thus, the present study involved the fabrication and characterization of powdered activated carbons impregnated with iron oxide nanoparticles (IONPACs) with respect to the simultaneous removal of BPA and NOM. The number of Fe ions loaded into the PAC pores was optimized in terms of exposure time. Impregnation with iron oxide reduced the surface area and pore volume, but the pore size was maintained. IONPAC adsorbents had considerably greater sorption capabilities for BPA and NOM compared to native, bare PAC particles. The adsorption capacities of BPA and NOM were in the following sequence: bare PAC

Nondestructive imaging of hidden figures on license plates by X-ray radiograph.

In this case, we investigated the modified license plates. The evidences had new embossing pressed serial numbers after erasing the original numbers on the license plates by hammering. The X-ray radiograph could visualize the hidden figures; those were virtually unseen by naked eyes or undetectable by ordinary photography. To reveal the erased figures, we performed image processing with computer software after X-ray radiographs. It proved to be an efficient nondestructive way to visualize the hidden original figures on metals.