Strong, tough and conductive single-network hydrogels based on deswelling and the salting-out effect.

In recent years, the continuous attention given to increasing the fracture toughness and Young's modulus of polymeric gels has gradually shifted from toughening strategies on double-network (DN) gels to single-network (SN) gels. The salt-soaking method has been adopted to realize the toughening of SN gels through the salting-out effect and deswelling, constructing dense network structures with simultaneously precipitated polymer chains and cross-links. By comparing the mechanical properties between salt-treated hydrogels and air-dried hydrogels, the increased polymer chain concentration is proved to promote energy transfer by enlarging the dissipation region size due to the unwinding and slippage of coiled chains during stretching. The newly formed cross-link points in salt-treated hydrogels are considered to consume more deformation energy during stretching. The synergistic effect in energy transfer and dissipation arising from increases in polymer fraction and cross-linking plays an indispensable role in toughening SN hydrogels. In addition, the soaking process introduces abundant free ions to endow hydrogels with prominent conductivity. Thus, this salt-soaking method provides a general approach to synthesize strong, tough and conductive hydrogels with applications in flexible electrical devices.

Strong and tough polysaccharide organohydrogels for strain, humidity and temperature sensors.

To avoid the potential toxicity of monomer residues in synthetic polymer based organohydrogels, natural polysaccharide-based organohydrogels are expected to be used in multi-functional wearable sensory systems, but most of them have unsatisfactory stiffness, strength and fracture toughness. Herein, a cooking and soaking strategy is proposed to prepare novel natural polysaccharide-based organohydrogels possessing outstanding stiffness, strength, toughness, freezing resistance, heating resistance and long-term durability. The agar organohydrogel exhibits a fracture stress of 3.3 MPa, a Young's modulus of 2.26 MPa and a fracture toughness of 14.8 kJ m-2, the κ-carrageenan organohydrogel exhibits a fracture stress of 3.3 MPa, a Young's modulus of 4.34 MPa and a fracture toughness of 11.0 kJ m-2, and the gellan organohydrogel exhibits a fracture stress of 1.2 MPa, a Young's modulus of 2.81 MPa and a fracture toughness of 5.4 kJ m-2. Furthermore, the agar organohydrogels are assembled into multi-functional wearable sensors by introducing NaCl as a conducting agent exhibiting responses to strain (5-150%), temperature (-15 to 60 °C) and humidity (11-97%), and possessing exceptional multi-sensory capabilities. Therefore, the developed strategy has shown a new pathway towards strengthening polysaccharide-based organohydrogels with potential for application in wearable sensory systems.

A bibliometric and visualized analysis of hepatic ischemia-reperfusion injury (HIRI) from 2002 to 2021.

Hepatic ischemia-reperfusion injury (HIRI) is a complex pathological phenomenon dominated by the innate immune system and involves a variety of immune cells. This condition frequently occurs during hepatectomy, liver transplantation or hemorrhagic shock. HIRI represents an important factor in the poor prognosis of patients after liver surgery. However, there is still a lack of effective intervention to reduce the incidence of HIRI. In this study, we aimed to describe the overall structure of scientific research on HIRI over the past 20 years and provide valuable information and guidelines for future researchers. Bibliometric analysis was used to comprehensively review developments in HIRI and changes in our understanding of HIRI over the past two decades. We identified a total of 4267 articles on HIRI that were published over the past 20 years of which basic research was predominant. Collaboration network analysis revealed that China, the University of California Los Angeles, and Ronald W Busuttil were the most influential country, institute, and scholar, respectively. Co-occurrence cluster analysis revealed that ischemic preconditioning, liver cirrhosis, hepatic I/R injury, autophagy, acute liver failure, oxygen, donation after circulatory death, Nlrp3, remote organ, and microdialysis were the top 10 clusters. Keyword burst detection indicated that autophagy, inflammation, and early allograft dysfunction represent the current research hotspots. In summary, this is the first bibliometric analysis of HIRI research. Our timely analysis of these hotpots and research trends may provide a framework for future researchers and further promote research on the key mechanisms and therapeutic measures in this field.

A meta-analysis for vaccine protection rate of duck hepatitis a virus in mainland China in 2009-2021.

BACKGROUND: Duck hepatitis A virus (DHAV) is a single-stranded, positive-strand small RNA virus that causes a very high mortality rate in ducklings. The DHAV-3 subtype incidence rate has recently increased in China, causing great economic losses to the waterfowl breeding industry. We analyzed the protection rate of DHAV vaccines used in mainland China from 2009 to 2021 and evaluated the effectiveness of vaccine prevention and control to reduce the economic losses caused by DHAV to the waterfowl breeding industry. We screened five electronic research databases and obtained 14 studies and patents on the protection efficiency of DHAV-1 and DHAV-3 vaccines. RESULTS: Meta-analysis demonstrated that immunized ducklings produced higher antibody levels and had a significantly higher survival rate than non-immunized ducklings [relative risk (RR) = 12, 95% confidence interval (CI) 6-26, P < 0.01]. The age of the ducks and vaccine valence did not affect protection efficiency. Data source analysis of the vaccine protection rate demonstrated that the vaccines conferred immune protection for ducklings in both small-scale experiments and large-scale clinical conditions. The analysis results revealed that although the vaccines conferred protection, the immune protective effect differed between small-scale experimental conditions and large-scale clinical conditions. This might have been due to non-standard vaccination and environmental factors. CONCLUSIONS: Domestic DHAV vaccines can protect ducklings effectively. The subjects immunized (breeding ducks or ducklings) and vaccine valence had no effect on the protective effect. Both small-scale experiments and large-scale clinical conditions conferred immune protection on ducklings, but vaccine immunization under small-scale experimental conditions had slightly better protective effects than large-scale clinical immunization.

Bismuth Incorporation in Palladium Hydride for the Electrocatalytic Ethanol Oxidation with Enhanced CO Tolerance.

Introducing nonmetal and oxophilic metal into palladium (Pd)-based catalysts is beneficial for boosting electrocatalysis, especially regarding the improvement of mass activity (MA) and CO tolerance. Herein, the stable bismuth-doped palladium hydride (Bi/PdH) networks have been successfully fabricated through a simple one-step method. The intercalation of interstitial H atoms expands the lattice of Pd, and the doping of oxophilic metal Bi restrains the adsorption of poisonous intermediates on the surface of Pd, thereby improving the activity and durability of the as-prepared catalysts in the ethanol oxidation reaction (EOR). The obtained Bi/PdH networks manifest a remarkable MA of 8.51 A·mgPd-1, which is 11.18 times higher than that of commercial Pd/C (0.76 A·mgPd-1). The CO-stripping analysis results indicate that Bi doping can significantly prohibit CO adsorption on the surface of the Bi/PdH networks. The density functional theory (DFT) calculations also reveal that Bi doping enhances the OH* adsorption on the catalyst surface and mitigates the interaction between Pd and CO* intermediates, providing deeper insights into the origin of the enhanced EOR activity and CO tolerance. This work describes an impactful path for producing high-performance and durable PdH-based nanocatalysts.

Cross talk between Cu excess and Fe deficiency in the roots of rice.

Copper (Cu) and iron (Fe) share similar characteristics and participate as coenzymes in several physiological processes. Both Cu excess and Fe deficiency result in chlorosis, however, the crosstalk between the two is not clear in rice. In this study, we performed transcriptome analysis for Cu excess and Fe deficiency in rice. Some WRKY family members (such as WRKY26) and some bHLH family members (such as late flowering) were selected as novel potential transcription factors involved in the regulation of Cu detoxification and Fe utilization, respectively. These genes were induced under corresponding stress conditions. Many Fe uptake-related genes were induced by Cu excess, while Cu detoxification-related genes were not induced by Fe deficiency. Meanwhile, some genes, such as metallothionein 3a, gibberellin 3beta-dioxygenase 2 and WRKY11, were induced by Cu excess but repressed by Fe deficiency. Concisely, our results highlight the crosstalk between Cu excess and Fe deficiency in rice. Cu excess caused Fe deficiency response, while Fe deficiency did not lead to Cu toxicity response. Metallothionein 3a might be responsible for Cu toxicity-induced chlorosis in rice. The crosstalk between Cu excess and Fe deficiency might be regulated by gibberellic acid.

A strong and tough gelatin/polyvinyl alcohol double network hydrogel actuator with superior actuation strength and fast actuation speed.

Hydrogels are widely used in actuators that are applied in numerous fields such as multifunctional sensors, soft robots, artificial muscles, manipulators and microfluidic valves, and yet their applications in soft robots and artificial muscles are often limited by low actuation strength and slow actuation speed. Here, we develop a hydrogel actuator with high actuation strength (contraction strength of 850 kPa), fast actuation speed (response time of 90 s) and high energy density (output working density of 72 kJ m-3) by introducing a storing-releasing elastic potential energy method into a double network hydrogel. The high actuation strength is owing to the double network hydrogel, which possesses a high elastic modulus of 1.3 MPa, fracture strength of 1.8 MPa, and fracture energy of 16 kJ m-2. The fast actuation speed is due to the storing-releasing elastic potential energy method, which stretches the hydrogel and locks the hydrogel at deformed shape under external stimuli to store the elastic potential energy and then makes the hydrogel contract rapidly under new stimuli to release the pre-stored energy. A capture actuator and a hand muscle actuator are fabricated to achieve strong and fast actuation. The hydrogel actuator has shown potential applications in soft robots and artificial muscles.

A rare presentation of type II Abernethy malformation and nephrotic syndrome: Case report and review.

Type II Abernethy malformation is an extremely reported congenital extrahepatic portosystemic shunt in complication with nephrotic syndrome. We present the case of an 8-year-old boy who presented with symptoms of type II Abernethy malformation and nephrotic syndrome. This diagnosis of this type II Abernethy malformation was based on physical examination, blood tests, urinalysis, nephrotic and hepatic function tests, routine clinical lipid measurements, abdominal ultrasonography, and computed tomographic angiography. A kidney biopsy revealed the pathological features of nephrotic syndrome. This is the second reported patient diagnosed with type II Abernethy malformation and nephrotic syndrome. Captopril treatment was effective in improving the symptoms of this case. A patient with type II Abernethy malformation related to immune complex-mediated glomerular injury was effectively improved with medication. Type II Abernethy malformation is a causative factor of immune complex-mediated glomerular injury in nephrotic syndrome. Captopril treatment significantly improved the symptoms in this case.

Effect of Rubus extract on TLR4/NF-kappa B signaling pathway in alcoholic liver fibrosis rats.

This study aims to explore the effect of the Rubus extract on the TLR4/NF-κB signaling pathway in alcoholic liver fibrosis rats. The alcoholic liver rat model was established by continuous ethanol gavage administration. Rats were divided randomly into six groups (i.e., blank control, model, 0.05g/kg Rubus extract, 0.125g/kg Rubus extract, 0.259 g/kg Rubus extract and positive control groups). Liver tissue and blood were collected after treatment for four weeks. The pathological changes in the liver were observed by HE and Masson staining methods. The hyaluronic acid (HA), TNF-α and IL-6 levels were determined by ELISA kits. The TLR4 and p-p65 protein expression levels in liver were detected by Western blot. The liver lesion degree was significantly decreased in the Rubus extract group, and a high concentration of the Rubus extract indicated a significant improvement. The TNF-α, HA and IL-6 levels in the Rubus extract and positive control groups were significantly lower than those of the model group (P<0.05). The TLR4 and p-p65 protein expression levels were also significantly decreased in the Rubus extract and positive control groups (P< 0.05) with a concentration dependence of Rubus extract. The Rubus extract could delay the development of alcoholic liver fibrosis through inhibiting the TLR4/NF-κB pathway activity.

Treating intrauterine adhesion using conditionally reprogrammed physiological endometrial epithelial cells.

BACKGROUND: There is unmet need for effective therapies of intrauterine adhesions (IUAs) that are common cause of menstrual disturbance and infertility, since current clinical procedures do not improve prognosis for patients with moderate to severe IUA, with a recurrence rate of 23-50%. Stem cell-based therapy has emerged as a therapeutic option with unsolved issues for IUA patients in the past few years. Primary endometrial epithelial cells for cell therapy are largely hampered with the extremely limited proliferation capacity of uterine epithelial cells. This study was to evaluate whether IUA is curable with conditionally reprogrammed (CR) endometrial epithelial cells. METHODS: Mouse endometrial epithelial cells (MEECs) were isolated from C57BL female mice, and long-term cultures of MEECs were established and maintained with conditional reprogramming (CR) method. DNA damage response analysis, soft agar assay, and matrigel 3D culture were carried out to determine the normal biological characteristics of CR-MEECs. The tissue-specific differentiation potential of MEECs was analyzed with air-liquid interface (ALI) 3D culture, hematoxylin and eosin (H&E) staining, Masson's trichrome and DAB staining, immunofluorescence assay. IUA mice were constructed and transplanted with CR-MEECs. Repair and mechanisms of MEECs transplantation in IUA mice were measured with qRT-PCR, Masson's trichrome, and DAB staining. RESULTS: We first successfully established long-term cultures of MEECs using CR approach. CR-MEECs maintained a rapid and stable proliferation in this co-culture system. Our data confirmed that CR-MEECs retained normal biological characteristics and endometrium tissue-specific differentiation potential. CR-MEECs also expressed estrogen and progesterone receptors and maintained the exquisite sensitivity to sex hormones in vitro. Most importantly, allogeneic transplantation of CR-MEECs successfully repaired the injured endometrium and significantly improved the pregnancy rate of IUA mice. CONCLUSIONS: Conditionally reprogrammed physiological endometrial epithelial cells provide a novel strategy in IUA clinics in a personalized or generalized manner and also serve as a physiological model to explore biology of endometrial epithelial cells and mechanisms of IUA.

Listeriosis during pregnancy: a retrospective cohort study.

BACKGROUND: Pregnancy-associated listeriosis is a severe infectious disease and potentially leads to fetal/neonatal fatal, while limited information on pregnancy-associated listeriosis is available in China. This study aimed to reveal the clinical characteristics and outcomes of pregnancy-associated listeriosis cases and provide references for treating and managing this disease. METHODS: We performed a retrospective study on maternal and neonatal patients with pregnancy-associated listeriosis. The clinical characteristics of pregnancy-associated listeriosis were studied, and the outcome determinants of neonatal listeriosis were explored. RESULTS: 14 cases of pregnancy-associated listeriosis were identified. The incidence of pregnancy-associated listeriosis in our hospital was 16.69/100,000 births. All of the 14 maternal patients eventually recovered after delivery shortly with no sequelae. None of the 12 mothers who delivered in this hospital received antepartum first-line empirical treatment. Among the 14 neonatal cases, 1 was late-onset listeriosis and 13 were early-onset cases; 11 survived and 3 died. Fatality rates were significantly higher in outborn neonates (P = 0.005). Besides, higher mortality rates were observed in neonates with lower birth weight (P = 0.038), gestational age < 28 weeks (P = 0.056), and Apgar score (5th min) < 5 (P = 0.056), with marginally significant differences. CONCLUSIONS: Pregnancy-associated listeriosis would bring disastrous effects to the neonatal cases, especially to the outborn, low birth weight, and low gestational age of neonates. Timely detection and treatment should be taken seriously for the key neonates. How to early detect L. monocytogenes infected cases, especially in the prenatal stage, remains a serious challenge.

Stiff and strong hydrogel tube with great mechanical properties and high stability in various solutions.

Hydrogel tubes are widely used in fields such as artificial blood vessels, drug delivery, biomedical scaffolds and cell adhesion, yet their application is often limited by unsatisfactory mechanical properties and poor stability in various solutions. Herein, a novel hydrogel tube exhibiting a remarkable mechanical performance and stability in various solutions is prepared by introducing a dual physically cross-linked double network (DN) hydrogel matrix. The obtained hydrogel tube can withstand ∼60 N load without fracture and be stretched to over twice its original length before and after immersing in various solutions. The great mechanical properties and stability in various solutions of hydrogel tubes are due to the introduction of a dual physically cross-linked poly(acrylamide-co-acrylic acid)/carboxymethylcellulose sodium/Fe3+ DN hydrogel, which possesses high elastic modulus (3.71 MPa), fracture energy (15.4 kJ m-2), and great stability in various solutions. In addition, the hydrogel tubes with different thickness, diameters, shapes and the multiple branched hydrogel tubes can also be fabricated to enable further functionalization for application requirements. Therefore, this new type of hydrogel tube presents tremendous potential for applications in biomedical and engineering fields.

GINS2 regulates the proliferation and apoptosis of colon cancer cells through PTP4A1.

Colon cancer is associated with high death rates worldwide and poses a serious threat to public health. GINS complex subunit 2 (GINS2) serves a carcinogenic role in many cancers, including gastric adenocarcinoma, ovarian cancer and pancreatic cancer. However, the specific function of GINS2 in the development of colon cancer has not been described in detail. The present study aimed to clarify the role of GINS2 in colon cancer. A Cell Counting Kit­8 assay, EdU staining, TUNEL and flow cytometry analyses were performed to determine the levels of cell viability, proliferation and apoptosis and to evaluate the cell cycle. Through the analysis of BioGrid, a Protein­Protein Interaction database, it was hypothesized that protein tyrosine phosphatase 4A1 (PTP4A1) is a protein that might interact with GINS2, which was then validated using a co­immunoprecipitation assay. mRNA and protein levels were measured using reverse transcription­quantitative PCR and western blotting, respectively. The results of the present study demonstrated that GINS2 expression levels were increased in colon cancer cells. Furthermore, GINS2 knockdown inhibited the proliferation of colon cancer cells, while the levels of cell cycle arrest and apoptosis were increased. By interacting with PTP4A1, GINS2 promoted the expression of PTP4A1, a novel p53 target. GINS2 knockdown was increased, while PTP4A1 overexpression decreased the protein level of p53. Notably, PTP4A1 overexpression partly reversed the effects of GINS2 downregulation on colon cancer cells. Therefore, the present study demonstrated that GINS2 regulated the proliferation and apoptosis of colon cancer cells through PTP4A1/p53 pathway, highlighting that GINS2 may serve as a novel molecular marker for colon cancer prevention and therapy.

The clinical characteristics and microbiological investigation of pediatric burn patients with wound infections in a tertiary hospital in Ningbo, China: A ten-year retrospective study.

Burn is one of the leading causes of death and disability in children worldwide, and wound infection is an excellent challenge in burn treatment. We performed a retrospective review of pediatric burn patients with wound infections to reveal their clinical data and investigate pathogens' distribution and drug resistance patterns to provide references for treatment. As a result, 330 pediatric burn patients with wound infections were identified; 65.8% (217/330) were < 2 years old. Most of the injuries were scalded and involved <10% total body surface area in size (TBSA), mainly causing II-degree burn and II + III-degree burn. Three hundred and fifty nine strains of pathogens were isolated, the primary pathogens were Staphylococcus aureus (45.4%) and Pseudomonas aeruginosa (18.7%). Both S. aureus and P. aeruginosa isolated from 2012 to 2016 were more likely to be multi-resistant than those isolated from 2017 to 2021, as they were significantly associated with resistance to ≥4 Clinical and Laboratory Standard Institute (CLSI) classes (p = 0.040 and 0.006, respectively). In conclusion, children aged <2 years old were the main pediatric burn patients with wound infections. The primary bacteria isolated from the wound were S. aureus and P. aeruginosa, with a decreasing tendency of multi-resistance.

Extremely stretchable and tough hybrid hydrogels based on gelatin, κ-carrageenan and polyacrylamide.

Nowadays, several approaches are being suggested to endow hydrogels with improved mechanical properties for practical applications as cartilage and skin replacements, soft electronics, and actuators. However, it remains a challenge to develop DN gels with both high fracture toughness and fracture stretch. Here, we introduce (bio)polyelectrolyte complexes (PECs) consisting of gelatin and κ-carrageenan as the first brittle network and covalently crosslinked polyacrylamide (PAAm) as the second stretchable network to fabricate a highly stretchable and notch-insensitive gelatin/κ-carrageenan/PAAm hydrogel. The unprecedented high stretchability (∼51.7) is ascribed to the reduction of stress concentration and defects in the network structure through the fracture of the PEC gel. In addition, a high fracture toughness (∼16053.34 J m-2) is achieved by effective energy transfer between the PECs and PAAm gel due to their covalent crosslinking, and efficient energy dissipation through destroying inter- and intramolecular interactions in the PEC gel.

DFT insights into the Ni-catalyzed regioselective hydrocarboxylation of unsaturated alkenes with CO2.

The nickel-catalyzed hydrocarboxylation of alkenes using carbon dioxide has recently become an appealing method to prepare functionalized carboxylic acids with high efficiency and regioselectivity. Herein, density functional theory (DFT) calculations were conducted on the Ni-catalyzed hydrocarboxylation of aryl-/alkyl-substituted alkenes with CO2. The α- and ß-carboxylation of aromatic and aliphatic olefins originate from distinct catalytic cycles: H-transfer-carboxylation and carboxylation-H-transfer pathways. The typical hydrometallation-carboxylation mechanism is unlikely because water/carbonic acid (H-resource) are inferior hydride donors.

An extremely tough and ionic conductive natural-polymer-based double network hydrogel.

Hydrogels are widely used in fields such as drug delivery, tissue regeneration, soft robotics and flexible smart electronic devices, yet their application is often limited by unsatisfactory mechanical behaviors. Among the various improvement strategies, double network (DN) hydrogels from synthetic polymers demonstrated impressive mechanical properties, while those from natural polymers were usually inferior. Here, a novel DN hydrogel composed fully of natural polymers exhibiting remarkable mechanical properties and conductivity is prepared by simply soaking a virgin gellan gum/gelatin composite hydrogel in a mixed solution of Na2SO4 and (NH4)2SO4. This hydrogel exhibits a tunable Young's modulus (0.08 to 42.6 MPa), good fracture stress (0.05 to 7.5 MPa), good fracture stretch (1.4 to 7.1), high fracture toughness (up to 27.7 kJ m-2), and high ionic conductivity (up to 11.4 S m-1 at f = 1 kHz). The improvement in the mechanical properties of the DN gel is attributed to the chain-entanglement crosslinking points introduced by SO42- in the gelatin network and the electrostatic interaction crosslinking points introduced by Na+ in the gellan gum network. The high ionic conductivity of the DN gel is attributed to the infiltration of the DN gel in a salt solution of high concentration. The developed gellan gum/gelatin DN hydrogel has shown a new pathway towards strengthening natural-polymer-based DN hydrogels and towards potential applications in biomedical engineering and flexible electronic devices.

Personalized drug testing in a patient with non-small-cell lung cancer using cultured cancer cells from pleural effusion.

OBJECTIVE: Patients with non-small-cell lung cancer (NSCLC) and primary or acquired resistance do not respond to targeted drugs. We explored whether cancer cells can be cultured from liquid biopsies from patients with primary resistance to tyrosine kinase inhibitors (TKIs). We aimed to predict patients' responses to drugs according to in vitro drug testing results. METHODS: Cancer cell cultures were established from the pleural effusion of a patient with TKI-resistant NSCLC using a conditional reprogramming technique. Phenotypic drug sensitivity tests were performed using the Cell Counting Kit-8 assay. We tested individual drugs and compared the synergistic and inhibitory effects of drug combinations. RESULTS: The results of our in vitro sensitivity test using the combination of cisplatin and pemetrexed were correlated with the patient's response. CONCLUSION: This represents the first successful report of predictive testing for combination therapy in patients with epidermal growth factor receptor-mutant NSCLC and primary TKI resistance. This strategy should be applicable to both chemotherapies and targeted therapies, and it will significantly improve the clinical treatment and management of patients with NSCLC and primary or acquired resistance to targeted therapies, as well as patients lacking targetable mutations.

Monoclonal Antibodies Specific to the Extracellular Domain of Histidine Kinase YycG of Staphylococcus epidermidis Inhibit Biofilm Formation.

Staphylococcus epidermidis is frequently associated with biofilm-related infections. Biofilms drastically reduce the efficacy of conventional antibiotics and the host immune system. In S. epidermidis biofilm formation, a major role is played by the YycG/YycF two-component system, and previous findings have indicated that inhibitors targeting the cytoplasmic HATPase_c domain of YycG kinase in S. epidermidis exhibit bactericidal and biofilm-killing activities. Therefore, we hypothesized that monoclonal antibodies (mAbs) against YycG extracellular (YycGex) domain would block the signal transduction and influence the biofilm formation of S. epidermidis. In this study, we screened out two YycGex-specific mAbs showing the highest affinity for the target, mAbs 2F3 and 1H1. These mAbs inhibited S. epidermidis biofilm formation in a dose-dependent manner, and at a concentration of 160 µg/mL, mAbs 2F3 and 1H1 caused 78.3 and 93.1% biofilm reduction, respectively, relative to normal mouse IgG control. When co-cultivated with YycGex mAbs, S. epidermidis cells showed diminished initial-adherence capacity, and the antibody treatment further led to a marked decrease in the synthesis of polysaccharide intercellular adhesin and in the transcriptional level of genes encoding proteins involved in biofilm formation. Lastly, we determined that the epitopes recognized by the two YycGex mAbs are located within aa 59-70 of the YycGex domain. It indicates that the YycGex domain may be a potential candidate as a vaccine for the prevention of S. epidermidis biofilm infections.

Long Term Culture of Human Kidney Proximal Tubule Epithelial Cells Maintains Lineage Functions and Serves as an Ex vivo Model for Coronavirus Associated Kidney Injury.

The mechanism of how SARS-CoV-2 causes severe multi-organ failure is largely unknown. Acute kidney injury (AKI) is one of the frequent organ damage in severe COVID-19 patients. Previous studies have shown that human renal tubule cells could be the potential host cells targeted by SARS-CoV-2. Traditional cancer cell lines or immortalized cell lines are genetically and phenotypically different from host cells. Animal models are widely used, but often fail to reflect a physiological and pathogenic status because of species tropisms. There is an unmet need for normal human epithelial cells for disease modeling. In this study, we successfully established long term cultures of normal human kidney proximal tubule epithelial cells (KPTECs) in 2D and 3D culture systems using conditional reprogramming (CR) and organoids techniques. These cells had the ability to differentiate and repair DNA damage, and showed no transforming property. Importantly, the CR KPTECs maintained lineage function with expression of specific transporters (SLC34A3 and cubilin). They also expressed angiotensin-converting enzyme 2 (ACE2), a receptor for SARS-CoV and SARS-CoV-2. In contrast, cancer cell line did not express endogenous SLC34A3, cubilin and ACE2. Very interestingly, ACE2 expression was around twofold higher in 3D organoids culture compared to that in 2D CR culture condition. Pseudovirion assays demonstrated that SARS-CoV spike (S) protein was able to enter CR cells with luciferase reporter. This integrated 2D CR and 3D organoid cultures provide a physiological ex vivo model to study kidney functions, innate immune response of kidney cells to viruses, and a novel platform for drug discovery and safety evaluation.