Development of cell-laden photopolymerized constructs with bioactive amorphous calcium magnesium phosphate for bone tissue regeneration via 3D bioprinting.

The synthesis of ideal bioceramics to guide the fate of cells and subsequent bone regeneration within the chemical, biological, and physical microenvironment is a challenging long-term task. This study developed amorphous calcium magnesium phosphate (ACMP) bioceramics via a simple co-precipitation method. The role of Mg2+ in the formation of ACMP is investigated using physicochemical and biological characterization at different Ca/Mg molar ratio of the initial reaction solution. Additionally, ACMP bioceramics show superior cytocompatibility and improved osteogenic differentiation of co-cultured MC3T3-E1 cells. Regulation of the microenvironment with Mg2+ can promote early-stage bone regeneration. For this, bioprinting technology is employed to prepare ACMP-modified 3D porous structures. Our hypothesis is that the incorporation of ACMP into methacrylated gelatin (GelMA) bioink can trigger the osteogenic differentiation of encapsulated preosteoblast and stimulate bone regeneration. The cell-laden ACMP composite structures display stable printability and superior cell viability and cell proliferation. Also, constructs loading the appropriate amount of ACMP bioceramic showed significant osteogenic differentiation activity compared to the pure GelMA. We demonstrate that the dissolved Mg2+ cation microenvironment in ACMP-modified composite constructs plays an effective biochemical role, and can regulate cell fate. Our results predict that GelMA/ACMP bioink has significant potential in patient-specific bone tissue regeneration.

Nanographene-Au fine-tuning to intensify plasmonic-resonance of polymeric hybrid bionanosystem for synergistic phototherapy and nerve photobiomodulation.

Here, we report the multi-photo-bioactivity of the plasmonic-nano graphitic coordinated polycaprolactone-based aligned nanofibrous scaffolds-based bionanosystem for photothermal breast and colon cancer therapies and peripheral nerve photobiomodulation. The size-optimized colloidal reduced graphene oxide (nRGO, 180 nm) nanosheets, for enhanced photothermal impact, were surface-functionalized with gold nanospheres (AuNPs) to prepare the nRGO@AuNP monodispersed nano-composite and then doped 2.0 mg of nRGO@AuNP in biocompatible and biodegradable polymer polycaprolactone (PCL) to fabricate the nRGO@AuNP-PCL (2.0 mg) plasmonic aligned nanofibrous scaffolds. More than 90% of cancer cells, breast cancer (MCF-7) as well as colon cancer (CT-26), ablated after 5 min of low NIR (808 nm) laser power (0.72 W/cm2) illumination with nRGO@AuNP-PCL (2.0 mg) aligned nanofibrous scaffolds. Besides, the nRGO@AuNP-PCL (2.0 mg) provided an extraordinary microenvironment for adhesion, nerve growth, proliferation, and differentiation of PC12 and S42 cells which mimics the natural extracellular matrix. The 2.5-fold increase in neurite length was observed with NIR illumination after 3 days whereas 1.7-fold was found without NIR illumination after 7 days in comparison to PCL (pure). The current findings will be useful to provide a new crucial approach for preparing biocompatible multifunctional composite plasmonic nanofibers as a highly efficient distinct platform for photothermal therapies and promising bioimplants to overcome the loss of sensation after cancer surgery through nerve photobiomodulation.

Conducting biointerface of spider-net-like chitosan-adorned polyurethane/SPIONs@SrO2-fMWCNTs for bone tissue engineering and antibacterial efficacy.

In pursuit of enhancing bone cell proliferation, this study delves into the fabrication of porous scaffolds through the integration of nanomaterials. Specifically, we present the development of highly conductive chitosan (CS) nanonets on fibro-porous polyurethane (PU) bio-membranes. These nanofibers comprise functionalized multiwall carbon nanotubes (fMWCNTs), well-dispersed superparamagnetic iron oxide (SPIONs), and strontium oxide (SrO2) nanoparticles. The resulting porous scaffold exhibits remarkable interfacial biocompatibility, antibacterial properties, and load-bearing capability. Through meticulous in vitro investigations, the CS-PU/SPIONs/SrO2-fMWCNTs nanofibrous scaffolds have demonstrated a propensity to promote bone cell regeneration. Notably, the integration of these nanomaterials has been found to upregulate crucial bone-related markers, including ALP, ARS, COL-I, RUNX2, and SPP-I. The evaluation of these markers, conducted through quantitative real-time polymerase chain reaction (qRT-PCR) and immunocytochemistry, substantiates the improved cell survival and enhanced osteogenic differentiation facilitated by the integrated nanomaterials. This comprehensive analysis underscores the efficacy of CS-PU/SPIONs/SrO2-fMWCNTs bioscaffolds in promoting MC3T3-E1 cell regeneration within, thereby holding promise for advancements in bone tissue engineering and regenerative medicine.

Electrochemical technique to develop surface-controlled polyaniline nano-tulips (PANINTs) on PCL-reinforced chitosan functionalized (CS-f-Fe2O3) scaffolds for stimulating osteoporotic bone regeneration.

Bone defects pose significant challenges in orthopedic surgery, often leading to suboptimal outcomes and complications. Addressing these challenges, we employed a three-electrode electrochemical system to fabricate surface-controlled polyaniline nano-tulips (PANINTs) decorated polycaprolactone (PCL) reinforced chitosan functionalized iron oxide nanoparticles (CS-f-Fe2O3) scaffolds. These structures were designed to emulate the natural extracellular matrix (ECM) and promote enhanced osseointegration by establishing a continuous interface between host bone and graft, thereby improving both biological processes and mechanical stability. In vitro experiments demonstrated that PANINTs-PCL/CS-f-Fe2O3 substrates significantly promoted the proliferation, differentiation, and spontaneous outgrowth and extension of MC3T3-E1 cell activity. The nanomaterials exhibited increased cell viability and osteogenic differentiation, as evidenced by elevated expression of bone-related markers such as ALP, ARS, COL-I, RUNX2, and SPP-I, as determined by qRT-PCR. Our findings underscore the regenerative potential of in situ cell culture systems for bone defects, emphasizing the targeted stimulation of essential cell subpopulations to facilitate rapid bone tissue regeneration.

Cu-MSNs and ZnO nanoparticles incorporated poly(ethylene glycol) diacrylate/sodium alginate double network hydrogel for simultaneous enhancement of osteogenic differentiation.

In this study, a double network (DN) hydrogel was synthesized using poly(ethylene glycol) diacrylate (PEGDA) and sodium alginate (SA), incorporating copper-doped mesoporous silica nanospheres (Cu-MSNs) and zinc oxide nanoparticles (ZnO NPs). The blending of PEGDA and SA (PS) facilitates the double network and improves the less porous microstructure of pure PEGDA hydrogel. Furthermore, the incorporation of ZnO NPs and Cu-MSNs into the hydrogel network (PS@ZnO/Cu-MSNs) improved the mechanical properties of the hydrogel (Compressive strength = ⁓153 kPa and Young's modulus = ⁓ 1.66 kPa) when compared to PS hydrogel alone (Compressive strength = ⁓ 103 kPa and Young's modulus = ⁓ 0.95 kPa). In addition, the PS@ZnO/Cu-MSNs composite hydrogel showed antibacterial activities against Staphylococcus aureus and Escherichia coli. Importantly, the PS@ZnO/Cu-MSNs hydrogel demonstrated excellent biocompatibility, enhanced MC3T3-E1 cell adhesion, proliferation, and significant early-stage osteoblastic differentiation, as evidenced by increased alkaline phosphatase (ALP), and improved calcium mineralization, as evidenced by increased alizarin red staining (ARS) activities. These findings point to the possible use of the PS@ZnO/Cu-MSNs composite hydrogel in bone tissue regeneration.

Noninvasive wearable sensor for the continuous monitoring of human sound and movement signals in real-time.

Recently, with the development of non-invasive human health monitoring technology including wearable devices, a flexible sensor that monitors 'human sound and movement signals' such as human voice and muscle movement is attracting attention. In this experiment, electrospun nanofibers were mixed with highly conductive nanoparticles and coated with polyaniline to detect the patient's electrical signals. Due to the high piezoelectric effect, nanofiber-based sensors do not require charging through a separate battery, so they can be used as self-powered devices. In addition, the LCR meter test confirmed that the sensor has a high capacitance due to its high conductivity and high sensitivity to electrical signals. The sensor produced in this study can visually estimate the electrical signal of the actual human body through real-time comparison with electromyography (EMG) measuring equipment, and it was confirmed that the error is small. This sensor is expected to be widely used in the medical field, from simple sound and movement signals to disease monitoring.

Benchtop and in Vitro Experiments of Novel Transform Stents for Trigeminal Neuralgia Treatment.

BACKGROUND: Trigeminal neuralgia (TN) is a debilitating condition characterized by sudden, excruciating facial pain due to neurovascular compression of the trigeminal nerve. Stent deployment can change the course of the superior cerebellar artery upwards, possibly releasing the root entry zone of the trigeminal nerve. We developed a novel stent, the Transform stent, for TN treatment, and evaluated its mechanical properties using benchtop and in vitro hemocompatibility tests. METHODS: We compared the performance of Transform and Enterprise stents in treating TN because they share similar self-expanding closed-cell features in the manufacturing process, are derived from nitinol tubes, and are fabricated through a laser-cutting process, but also because only the safety of Enterprise stents deployed in intracranial arteries has been reported clinically. All benchtop measurements, including radial force, trackability, bending stiffness, and conformability, were performed thrice for each stent model, and their average values are presented. RESULTS: Transform stents showed higher radial forces in vessels of diameters ranging from 1.0 mm than Enterprise stents. The trackability of the Transform stent was better than that of the Enterprise stent in a neurovascular model. Bending stiffness was stronger in the Transform stent whereas conformability was superior in the Enterprise stent. No significant thrombogenic issues were observed in the in vitro hemocompatibility tests. CONCLUSIONS: This study demonstrated the Transform stent as a potential option and paved the way for innovative endovascular approaches for the future TN treatment. Namely, the study confirmed that the characteristics of Transform stents at benchtop and in vitro evaluations may be used as a first step for studies such as in vivo pre- and clinical studies.

Strong intramolecular charge-transfer effect strengthening naphthoquinone-based chemosensor: Experimental and theoretical evaluation.

An aminophenol-linked naphthoquinone-based fluorometric and colorimetric chemosensor 2-chloro-3-((3-hydroxyphenyl) amino) naphthalene-1,4-dione (2CAN-Dione) was synthesized for selective detection of Sn2+ ion in aqueous solution. The amine and conversion of carbonyl into carboxyl groups play a vital role in the sensing mechanism when Sn2+ is added to 2CAN-Dione. Comprehensive characterization of the sensor was carried out using standard spectral and analytical approaches. Because of the intramolecular charge transfer (ICT) effect and the turn-on sensing mode, the strong fluorometric emission towards Sn2+ was observed at about 435 nm. The chemosensor exhibited good selectivity for Sn2+ in the presence of coexisting metal ions. An improved linear connection was established with a low limit of detection (0.167 µM). FT-IR, 1H NMR, 13C NMR, and quantum chemistry methods were performed to verify the binding coordination mechanism. The chemosensing probe 2CAN-Dione was successfully employed in bioimaging investigations, demonstrating that it is a reliable fluorescent marker for Sn2+ in human cancer cells.

Construction of a PEGDA/chitosan hydrogel incorporating mineralized copper-doped mesoporous silica nanospheres for accelerated bone regeneration.

Hydrogels, integrating diverse biocompatible materials, have emerged as promising candidates for bone repair applications. This study presents a double network hydrogel designed for bone tissue engineering, combining poly(ethylene glycol) diacrylate (PEGDA) and chitosan (CS) crosslinked through UV polymerization and ionic crosslinking. Concurrently, copper-doped mesoporous silica nanospheres (Cu-MSNs) were synthesized using a one-pot method. Cu-MSNs underwent additional modification through in-situ biomineralization, resulting in the formation of an apatite layer. Polydopamine was employed to facilitate the deposition of Calcium (Ca) and Phosphate (P) ions on the surface of Cu-MSNs (Cu-MSNs/PDA@CaP). Composite hydrogels were created by integrating varied concentrations of Cu-MSNs/PDA@CaP (25, 50, 100, 150, 200 µg/mL). Characterization unveiled distinctive interconnected porous structures within the composite hydrogel, showcasing a notable 169.6 % enhancement in compressive stress (elevating from 89.01 to 240.19 kPa) compared to pure PEGDA. In vitro biocompatibility experiments illustrated that the composite hydrogel maintained elevated cell viability (up to 106.6 %) and facilitated rapid cell proliferation over 7 days. The hydrogel demonstrated a substantial 57.58 % rise in ALP expression and a surprising 235.27 % increase in ARS staining. Moreover, it significantly enhanced the expression of crucial osteogenic genes, such as run-related transcription factors 2 (RUNX2), collagen 1a1 (Col1a1), and secreted phosphoprotein 1 (Spp1), establishing it as a promising scaffold for bone regeneration. This study shows how Cu-MSNs/PDA@CaP were successfully integrated into a double network hydrogel, resulting in a composite material with good biological responses. Due to its improved characteristics, this composite hydrogel holds the potential for advancing bone regeneration procedures.

Amikacin sulphate loaded chitosan-diopside nanoparticles composite scaffold for infectious wound healing.

A wound dressing material should inhibit infections that may occur at the wound site, and at the same time, it should enhance the healing process. In this study, we developed an amikacin sulphate (AK) incorporated chitosan (Ch) and Diopside nanoparticles composite dressing (Ch-nDE-AK) for controlling wound infection and healing. The diopside nanoparticles (nDE) were prepared using sol-gel synthesis and characterized using XRD, FT-IR, and FESEM. nDE shows a size range of 142 ± 31 nm through FESEM analysis. Later, the developed composite dressing was characterized using SEM, EDS, and FT-IR analysis. Ch-nDE-AK dressing possesses a porous nature that will aid in easy cell infiltration and proliferation. The swelling studies indicated the expansion capability of the scaffold when applied to the injured site. Ch-nDE-AK scaffold showed a 69.6 ± 8.2 % amikacin sulphate release up to 7 days, which indicates the sustained release of the drug from Ch-nDE-AK scaffold. The drug release data was subjected to various kinetics models and was observed to follow the Higuchi model. The scaffold showed antibacterial activity against ATCC strains of S. aureus and E. coli for 7 days by in vitro. Ch-nDE-AK scaffold also showed antibacterial activity against S. aureus and E. coli clinical strains in vitro. The ex vivo antibacterial study confirmed the antibacterial ability of Ch-nDE-AK scaffold against S. aureus and E. coli. Ch-nDE-AK scaffold also exhibits anti-biofilm activity against S. aureus and E. coli. The Ch-nDE-AK scaffold showed cytocompatibility and cell attachment to fibroblast cells. Additionally, the scratch assay using fibroblast cells confirmed the role of the nDE in the scaffold, helping in cell migration. Thus, the developed Ch-nDE-AK dressing can potentially be used to treat infectious wound healing.

Uncovering the clinicopathological features of early recurrence after surgical resection of pancreatic cancer.

To identify risk factors and biomarker for early recurrence in patients diagnosed with pancreatic cancer who undergo curative resection. Early recurrence after curative resection of pancreatic cancer is an obstacle to long-term survival. We retrospectively reviewed 162 patients diagnosed with pancreatic cancer who underwent curative resection. Early recurrence was defined as recurrence within 12 months of surgery. We selected S100A2 as a biomarker and investigated its expression using immunohistochemistry. Of the total, 79.6% (n = 129) of patients received adjuvant chemotherapy after surgery and 117 (72.2%) experienced recurrence, of which 73 (45.1%) experience early recurrence. In multivariate analysis, age < 60 years, presence of lymph node metastasis, and no adjuvant chemotherapy were significantly associated with early recurrence (all P < 0.05). The proportion of patients with high S100A2 expression (H-score > 5) was significantly lower in the early recurrence group (41.5% vs. 63.3%, P = 0.020). The cumulative incidence rate of early recurrence was higher in patients with an S100A2 H-score < 5 (41.5% vs. 63.3%, P = 0.012). The median overall survival of patients with higher S100A2 expression was longer than those with lower S100A2 expression (median 30.1 months vs. 24.2 months, P = 0.003). High-risk factors for early recurrence after surgery for pancreatic cancer include young age, lymph node metastasis, and no adjuvant therapy. Neoadjuvant treatment or intensive adjuvant therapy after surgery may improve the prognosis of patients with high-risk signatures. In patients who receive adjuvant therapy, high S100A2 expression is a good predictor.

Integrative analysis of spatial and single-cell transcriptome data from human pancreatic cancer reveals an intermediate cancer cell population associated with poor prognosis.

BACKGROUND: Recent studies using single-cell transcriptomic analysis have reported several distinct clusters of neoplastic epithelial cells and cancer-associated fibroblasts in the pancreatic cancer tumor microenvironment. However, their molecular characteristics and biological significance have not been clearly elucidated due to intra- and inter-tumoral heterogeneity. METHODS: We performed single-cell RNA sequencing using enriched non-immune cell populations from 17 pancreatic tumor tissues (16 pancreatic cancer and one high-grade dysplasia) and generated paired spatial transcriptomic data from seven patient samples. RESULTS: We identified five distinct functional subclusters of pancreatic cancer cells and six distinct cancer-associated fibroblast subclusters. We deeply profiled their characteristics, and we found that these subclusters successfully deconvoluted most of the features suggested in bulk transcriptome analysis of pancreatic cancer. Among those subclusters, we identified a novel cancer cell subcluster, Ep_VGLL1, showing intermediate characteristics between the extremities of basal-like and classical dichotomy, despite its prognostic value. Molecular features of Ep_VGLL1 suggest its transitional properties between basal-like and classical subtypes, which is supported by spatial transcriptomic data. CONCLUSIONS: This integrative analysis not only provides a comprehensive landscape of pancreatic cancer and fibroblast population, but also suggests a novel insight to the dynamic states of pancreatic cancer cells and unveils potential therapeutic targets.

Current status of nutritional provision and effects of nutritional support on the clinical outcomes of acute kidney injury requiring continuous renal replacement therapy in the surgical intensive care unit.

BACKGROUND AND OBJECTIVES: Patients with acute kidney injury requiring continuous renal replacement therapy are at high risk of malnutrition. Nutritional support is an important part of treatment for patients with critical illness admitted to the intensive care unit. We aimed to investigate the status of nutritional provision and the effects of nutritional support on clinical outcomes. METHODS AND STUDY DESIGN: Our institution's medical records (from January 1, 2020, to December 31, 2021) were analyzed in this retrospective cohort study. We included 43 patients aged >18 years who received continuous renal replacement therapy for acute kidney injury in the surgical intensive care unit. RESULTS: The demographic characteristics were similar between the survivor and non-survivor groups. The protein supply per body weight (0.88 ± 0.37 g/kg vs. 0.47 ± 0.53 g/kg, p = 0.029) and the proportion of patients who met the target protein level (58.9 ± 24.9% vs. 30.8 ± 34.9%, p = 0.022) were significantly higher in the survivor group. Approximately 79.1% of the patients had a high malnutrition risk with a modified Nutrition Risk in the Critically Ill score of ≥5. The lengths of hospital and intensive care unit stays were longer in the high nutritional risk group compared with that in the low nutritional risk group, but the result was not significant. CONCLUSIONS: The nutritional amount provided in patients with critical illness is significantly lesser than the recommended amount. Ensuring proper nutritional support can improve the clinical outcomes.

Successful perioperative management with damage control surgery following cardiac arrest due to massive postpartum hemorrhage: A case report.

INTRODUCTION: Although declining, maternal mortality due to postpartum hemorrhage (PPH) remains significant. Here we report the case of a 31-year-old primipara patient admitted with cardiac arrest due to PPH. CASE PRESENTATION: Labor was induced at gestational week 39, and the infant was delivered rapidly. Cardiac arrest due to PPH occurred during the transfer to our hospital, and the patient underwent cardiopulmonary resuscitation upon arrival to the emergency room. On admission, her hemoglobin level was 0.7 g/dL and she was in hypovolemic shock. Resuscitation and hysterectomy were performed immediately, including damage control surgery and gauze packing, to control the diffuse oozing bleeding due to severe disseminated intravascular coagulation. Relaparotomy for hemostasis was subsequently performed because of a decrease in hemoglobin level and blood pressure, and gauze packing was reinserted with temporary abdominal closure. Two days later, the abdominal wall was closed after confirming the absence of bleeding and the patient recovered well without further intervention. CONCLUSION: A prompt and assertive intensive response through collaborative efforts, utilizing feasible damage control surgery, can elegantly salvage uncontrolled bleeding in PPH patients with disseminated intravascular coagulation.

Synergistic Trimetallic Nanocomposites as Visible-NIR-Sunlight-Driven Photocatalysts for Efficient Artificial Photosynthesis.

Here, we report monodispersed tricomponent MnNSs-SnO2@Pt and MnNFs-SnO2@Pt nanocomposites prepared by simultaneous SnO2 and Pt nanodot coating on Mn nanospheres (MnNSs) and Mn nanoflowers (MnNFs) for highly efficient CO2 photoreduction in visible-NIR-sunlight irradiation. MnNFs-SnO2@Pt showed higher efficiency with a quantum yield of 3.21% and a chemical yield of 5.45% for CO2 conversion under visible light irradiation for HCOOH formation with 94% selectivity. Similarly, MnNFs-SnO2@Pt displayed significant photocatalytic efficiency in NIR and sunlight irradiation for HCOOH yield. MnNFs-SnO2@Pt nanocomposites also showed robust morphology and sustained structural stability with shelf-life for at least 1 year and were utilized for at least 10 reaction cycles without losing significant photocatalytic efficiency. The high surface area (94.98 m2/g), efficient electron-hole separation, and Pt-nanodot support in MnNFs--SnO2@Pt contributed to a higher photocatalytic efficacy toward CO2 reduction.

Development and Application of an Active Pharmacovigilance Framework Based on Electronic Healthcare Records from Multiple Centers in Korea.

INTRODUCTION: With the availability of retrospective pharmacovigilance data, the common data model (CDM) has been identified as an efficient approach towards anonymized multicenter analysis; however, the establishment of a suitable model for individual medical systems and applications supporting their analysis is a challenge. OBJECTIVE: The aim of this study was to construct a specialized Korean CDM (K-CDM) for pharmacovigilance systems based on a clinical scenario to detect adverse drug reactions (ADRs). METHODS: De-identified patient records (n = 5,402,129) from 13 institutions were converted to the K-CDM. From 2005 to 2017, 37,698,535 visits, 39,910,849 conditions, 259,594,727 drug exposures, and 30,176,929 procedures were recorded. The K-CDM, which comprises three layers, is compatible with existing models and is potentially adaptable to extended clinical research. Local codes for electronic medical records (EMRs), including diagnosis, drug prescriptions, and procedures, were mapped using standard vocabulary. Distributed queries based on clinical scenarios were developed and applied to K-CDM through decentralized or distributed networks. RESULTS: Meta-analysis of drug relative risk ratios from ten institutions revealed that non-steroidal anti-inflammatory drugs (NSAIDs) increased the risk of gastrointestinal hemorrhage by twofold compared with aspirin, and non-vitamin K anticoagulants decreased cerebrovascular bleeding risk by 0.18-fold compared with warfarin. CONCLUSION: These results are similar to those from previous studies and are conducive for new research, thereby demonstrating the feasibility of K-CDM for pharmacovigilance. However, the low quality of original EMR data, incomplete mapping, and heterogeneity between institutions reduced the validity of the analysis, thus necessitating continuous calibration among researchers, clinicians, and the government.

Rice husk-derived mesoporous biogenic silica nanoparticles for gravity chromatography.

Biogenic silica nanoparticle is a superb alternative to synthetic silica because of their highly active, polar, and porous nanostructure with a large interior area. Among the available agricultural bioresources, biogenic silica extracted from rice husks could be a simple, easily available, and cost-effective resource to use as the stationary phase for the column chromatographic technique. In the present study, highly pure amorphous biogenic silica nanoparticles (bSNPs) were synthesized using rice husk by a controlled combustion route followed by the sol-gel method. The bSNPs show better performance for the separation and isolation of ortho- and para-nitrophenol and nitroaniline. The outstanding performance of the as-synthesized bSNPs is attributed to the high surface area, high porosity, and presence of Si-OH polar bonds. These preliminary findings imply that rice husk, an agricultural waste, could be an alternative source of silica and applicable as a stationary phase in column chromatography.

A TEAD2-Driven Endothelial-Like Program Shapes Basal-Like Differentiation and Metastasis of Pancreatic Cancer.

BACKGROUND & AIMS: Pancreatic ductal adenocarcinoma (PDA), with its highly metastatic propensity, is one of the most lethal subtypes of pancreatic cancer. Although recent large-scale transcriptomic studies have demonstrated that heterogeneous gene expressions play an essential role in determining molecular phenotypes of PDA, biological cues for and consequences of distinct transcriptional programs remain unclear. METHODS: We developed an experimental model that enforces the transition of PDA cells toward a basal-like subtype. We combined epigenome and transcriptome analyses with extensive in vitro and in vivo evaluations of tumorigenicity to demonstrate the validity of basal-like subtype differentiation in association with endothelial-like enhancer landscapes via TEA domain transcription factor 2 (TEAD2). Finally, we used loss-of-function experiments to investigate the importance of TEAD2 in regulating reprogrammed enhancer landscape and metastasis in basal-like PDA cells. RESULTS: Aggressive characteristics of the basal-like subtype are faithfully recapitulated in vitro and in vivo, demonstrating the physiological relevance of our model. Further, we showed that basal-like subtype PDA cells acquire a TEAD2-dependent proangiogenic enhancer landscape. Genetic and pharmacologic inhibitions of TEAD2 in basal-like subtype PDA cells impair their proangiogenic phenotypes in vitro and cancer progression in vivo. Last, we identify CD109 as a critical TEAD2 downstream mediator that maintains constitutively activated JAK-STAT signaling in basal-like PDA cells and tumors. CONCLUSIONS: Our findings implicate a TEAD2-CD109-JAK/STAT axis in the basal-like differentiated pancreatic cancer cells and as a potential therapeutic vulnerability.

L-cysteine aided polyaniline capped SrO2 nanoceramics: Assessment of MC3T3-E1-arbitrated osteogenesis and anti-bactericidal efficacy on the polyurethane 2D nanofibrous substrate.

Fabricating bioartificial bone graft ceramics retaining structural, mechanical, and bone induction properties akin to those of native stem-cell niches is a major challenge in the field of bone tissue engineering and regenerative medicine. Moreover, the developed materials are susceptible to microbial invasion leading to biomaterial-centered infections which might limit their clinical translation. Here, we successfully developed biomimetic porous scaffolds of polyurethane-reinforcedL-cysteine-anchored polyaniline capped strontium oxide nanoparticles to improve the scaffold's biocompatibility, osteo-regeneration, mechanical, and antibacterial properties. The engineered nanocomposite substrate PU/L-Cyst-SrO2 @PANI (0.4 wt%) significantly promotes bone repair and regeneration by modulating osteolysis and osteogenesis. ALP activity, collagen-I, ARS staining, as well as biomineralization of MC3T3-E1 cells, were used to assess the biocompatibility and cytocompatibility of the developed scaffolds in vitro, confirming that the scaffold provided a favorable microenvironment with a prominent effect on cell growth, proliferation, and differentiation. Furthermore, osteogenic protein markers were studied using qRT-PCR with expression levels of runt-related transcription factor 2 (RUNX2), secreted phosphoprotein 1 (Spp-I), and collagen type I (Col-I). The overall results suggest that PU/L-Cyst-SrO2 @PANI (0.4 wt%) scaffolds showed superior interfacial biocompatibility, antibacterial properties, load-bearing ability, and osteoinductivity as compared to pristine PU. Thus, prepared bioactive nanocomposite scaffolds perform as a promising biomaterial substrate for bone tissue regeneration.

Risk factors for Pneumocystis pneumonia with acute respiratory failure among kidney transplant recipients.

PURPOSE: One of the rare life-threatening fungal infections is pneumocystis pneumonia (PCP). Immunocompromised patients are the main vulnerable population. We investigate the risk factors associated with the development of severe PCP infection with acute respiratory failure after kidney transplantation. MATERIALS AND METHODS: This is a retrospective, single-center, case-control study. PCP patients who are kidney transplant recipients and required high-flow oxygen support or mechanical ventilation between March 2009 and February 2017 were included in the study. The comparison was conducted between the non-severe and severe PCP groups. To identify associated risk factors, we performed univariate and multivariate logistic regression. RESULTS: Among the total 2,330 kidney transplant recipients, 50 patients (2.1%) were diagnosed with PCP. Of these, 27 patients (54.0%) had severe PCP and 7 patients (14.0%) died, all of them were severe PCP patients. In the severe PCP group, the time from transplantation to PCP diagnosis (23.4 ± 24.9 months vs. 13.7 ± 9.9 months, p = 0.090) was insignificantly faster than in the non-severe PCP group. According to multiple logistic regression analysis, the significant risk factors associated with severe PCP were as follows, age (odds ratios (OR) 1.07; 95% confidence intervals (CI): 1.01-1.13; p = 0.027), time from transplantation to PCP diagnosis (odds ratios (OR) 0.92; 95% confidence intervals (CI): 0.86-0.99; p = 0.024), lymphopenia (OR 6.48; 95% CI: 1.05-40.09; p = 0.044), and history of acute rejection within 1 year (OR 8.28; 95% CI: 1.29-53.20; p = 0.026). CONCLUSION: Patients who have lymphopenia at the time of hospital admission or have been recently treated with acute rejection are more likely to progress to severe PCP, requiring intensive monitoring and aggressive treatment.