The impact of restrictive blood transfusion on the safety of patients with esophageal varices after endoscopic variceal ligation: A single-center retrospective study.

An investigation was conducted to examine the impact of restrictive blood transfusion on the safety of early rebleeding following endoscopic variceal ligation (EVL) in patients with liver cirrhosis. Data were collected from patients with cirrhosis and esophageal varices who underwent EVL at the Affiliated Hospital of North Sichuan Medical College between September 2021 and March 2023. Clinical information, including serum albumin levels, hemoglobin (Hb) levels, liver function classification, and the occurrence of early rebleeding, was recorded. Patients were divided into 2 groups based on their Hb levels: 60 g/L to 90 g/L (restrictive blood transfusion) or Hb ≥ 90 g/L after EVL. The impact of restrictive transfusion on the post-ligation safety of EVL was observed. A total of 246 cirrhotic patients were included in the analysis. Significant differences were found in Hb levels, liver function classification, early rebleeding rates, length of hospital stay, and hospitalization expenses between the restrictive transfusion and Hb ≥ 90 g/L groups. The early rebleeding rate was significantly varied between the groups with different Hb levels after EVL. Multivariate logistic analysis revealed that restrictive blood transfusion (OR = 4.61, 95% CI: 1.06-19.99; P = .041), Hb (OR = 0.96, 95% CI: 0.95-0.97; P < .001), and Child-Pugh class C (OR = 6.37, 95% CI: 1.28-31.67; P = .024) were identified as independent factors influencing early rebleeding. Our findings suggest that the risk of early rebleeding in cirrhotic patients after EVL may be increased by restrictive blood transfusion, and this should be further investigated in future research.

A Review of Type 1 and Type 2 Intraductal Papillary Neoplasms of the Bile Duct.

Intraductal papillary neoplasm of the bile duct (IPNB) is a heterogeneous disease similar to intraductal papillary mucinous neoplasm of the pancreas. These lesions have been recognized as one of the three major precancerous lesions in the biliary tract since 2010. In 2018, Japanese and Korean pathologists reached a consensus, classifying IPNBs into type l and type 2 IPNBs. IPNBs are more prevalent in male patients in East Asia and are closely related to diseases such as cholelithiasis and schistosomiasis. From a molecular genetic perspective, IPNBs exhibit early genetic variations, and different molecular pathways may be involved in the tumorigenesis of type 1 and type 2 IPNBs. The histological subtypes of IPNBs include gastric, intestinal, pancreaticobiliary, or oncocytic subtypes, but type 1 IPNBs typically exhibit more regular and well-organized histological features than type 2 IPNBs and are more commonly found in the intrahepatic bile ducts with abundant mucin. Due to the rarity of these lesions and the absence of specific clinical and laboratory features, imaging is crucial for the preoperative diagnosis of IPNB, with local bile duct dilation and growth along the bile ducts being the main imaging features. Surgical resection remains the optimal treatment for IPNBs, but negative bile duct margins and the removal of lymph nodes in the hepatic hilum significantly improve the postoperative survival rates for patients with IPNBs.

LbSakA-mediated phosphorylation of the scaffolding protein LbNoxR in the ectomycorrhizal basidiomycete Laccaria bicolor regulates NADPH oxidase activity, ROS accumulation and symbiosis development.

Ectomycorrhizal symbiosis, which involves mutually beneficial interactions between soil fungi and tree roots, is essential for promoting tree growth. To establish this symbiotic relationship, fungal symbionts must initiate and sustain mutualistic interactions with host plants while avoiding host defense responses. This study investigated the role of reactive oxygen species (ROS) generated by fungal NADPH oxidase (Nox) in the development of Laccaria bicolor/Populus tremula × alba symbiosis. Our findings revealed that L. bicolor LbNox expression was significantly higher in ectomycorrhizal roots than in free-living mycelia. RNAi was used to silence LbNox, which resulted in decreased ROS signaling, limited formation of the Hartig net, and a lower mycorrhizal formation rate. Using Y2H library screening, BiFC and Co-IP, we demonstrated an interaction between the mitogen-activated protein kinase LbSakA and LbNoxR. LbSakA-mediated phosphorylation of LbNoxR at T409, T477 and T480 positively modulates LbNox activity, ROS accumulation and upregulation of symbiosis-related genes involved in dampening host defense reactions. These results demonstrate that regulation of fungal ROS metabolism is critical for maintaining the mutualistic interaction between L. bicolor and P. tremula × alba. Our findings also highlight a novel and complex regulatory mechanism governing the development of symbiosis, involving both transcriptional and posttranslational regulation of gene networks.

Hybrid Microneedle-Mediated Transdermal Delivery of Atorvastatin Calcium-Loaded Polymeric Micelles for Hyperlipidemia Therapy.

Hyperlipidemia has been a huge challenge to global health, leading to the cardiovascular disease, hypertension, and diabetes. Atorvastatin calcium (AC), a widely prescribed drug for hyperlipidemia, faces huge challenges with oral administration due to poor water solubility and hepatic first-pass effects, resulting in low therapeutic efficacy. In this work, we designed and developed a hybrid microneedle (MN) patch system constructed with soluble poly(vinyl alcohol) (PVA) and AC-loaded polymeric micelles (AC@PMs) for transdermal delivery of AC to enhance the hyperlipidemia therapy. We first prepared various AC@PM formulations self-assembled from mPEG-PLA and mPEG-PLA-PEG block copolymers using a dialysis method and evaluated the physicochemical properties in combination with experiment skills and dissipative particle dynamics (DPD) simulations. Then, we encapsulated the AC@PMs into the PVA MN patch using a micromold filling method, followed by characterizing the performances, especially the structural stability, mechanical performance, and biosafety. After conducting in vivo experiments using a hyperlipidemic rat model, our findings revealed that the hybrid microneedle-mediated administration exhibited superior therapeutic efficacy when compared to oral delivery methods. In summary, we have successfully developed a hybrid microneedle (MN) patch system that holds promising potential for the efficient transdermal delivery of hydrophobic drugs.

Three-dimensional ultrafast charge-density-wave dynamics in CuTe.

Charge density waves (CDWs) involved with electronic and phononic subsystems simultaneously are a common quantum state in solid-state physics, especially in low-dimensional materials. However, CDW phase dynamics in various dimensions are yet to be studied, and their phase transition mechanism is currently moot. Here we show that using the distinct temperature evolution of orientation-dependent ultrafast electron and phonon dynamics, different dimensional CDW phases are verified in CuTe. When the temperature decreases, the shrinking of c-axis length accompanied with the appearance of interchain and interlayer interactions causes the quantum fluctuations (QF) of the CDW phase until 220 K. At T < 220 K, the CDWs on the different ab-planes are finally locked with each other in anti-phase to form a CDW phase along the c-axis. This study shows the dimension evolution of CDW phases in one CDW system and their stabilized mechanisms in different temperature regimes.

Total contents, fractionation and bioaccessibility of nine heavy metals in household dust from 14 cities in China.

The potential health risk caused by long-term exposure to heavy metals in household dust is not only depended on their total content, but also bioaccessibility. In this study, twenty-one dust samples were collected from residential buildings, schools, and laboratories in 14 provincial-capital/industrial cities of China, aiming to evaluate the total contents, fractionation, bioaccessibility and health risks of nine heavy metals (As, Cd, Cr, Ni, Pb, Mn, Zn, Fe, and Cu). Results showed that the highest levels of Cd, Cr, Ni and Zn were found in laboratory dust, As, Pb and Mn in school dust, and Fe and Cu in residential dust, indicating different source profiles of the heavy metals. The mean bioaccessibility of the heavy metals across all samples as evaluated using SBRC (Solubility Bioavailability Research Consortium), IVG (In Vitro Gastrointestinal), and PBET (Physiologically Based Extraction Test) assays was 58.4%, 32.4% and 17.2% in gastric phase (GP), and 24.9%, 21.9% and 9.39% in intestinal phase (IP), respectively. Cadmium had the highest content in the fractions of E1+C2 (43.7%), as determined by sequential extraction, and Pb, Mn, and Zn had a higher content in E1+C2+F3 (64.2%, 67.2%, 78.8%), resulting in a higher bioaccessibility of these heavy metals than others. Moreover, the bioaccessibility of most heavy metals was inversely related to dust pH (R = -0.18 in GP; -0.18 in IP; P < 0.01) and particle size, while a positive correlation was observed with total organic carbon (R = 0.40 in GP; 0.38 in IP; P < 0.01). The exposure risk calculated by the highest bioaccessibility was generally lower than that calculated by the total content. However, Pb in one school dust sample had an unacceptable carcinogenic risk (adult risk = 1.19 × 10-4; child risk = 1.08 × 10-4). This study suggests that bioaccessibility of heavy metals in household dust is likely related to geochemical fractions and physical/chemical properties. Further research is needed to explore the sources of bioaccessible heavy metals in household dust.

Histone methyltransferase Ezh2 coordinates mammalian axon regeneration via regulation of key regenerative pathways.

Current treatments for neurodegenerative diseases and neural injuries face major challenges, primarily due to the diminished regenerative capacity of neurons in the mammalian CNS as they mature. Here, we investigated the role of Ezh2, a histone methyltransferase, in regulating mammalian axon regeneration. We found that Ezh2 declined in the mouse nervous system during maturation but was upregulated in adult dorsal root ganglion neurons following peripheral nerve injury to facilitate spontaneous axon regeneration. In addition, overexpression of Ezh2 in retinal ganglion cells in the CNS promoted optic nerve regeneration via both histone methylation-dependent and -independent mechanisms. Further investigation revealed that Ezh2 fostered axon regeneration by orchestrating the transcriptional silencing of genes governing synaptic function and those inhibiting axon regeneration, while concurrently activating various factors that support axon regeneration. Notably, we demonstrated that GABA transporter 2, encoded by Slc6a13, acted downstream of Ezh2 to control axon regeneration. Overall, our study underscores the potential of modulating chromatin accessibility as a promising strategy for promoting CNS axon regeneration.

Discovery and characterization of cross-reactive intrahepatic antibodies in severe alcoholic hepatitis.

The pathogenesis of antibodies in severe alcoholic hepatitis (SAH) remains unknown. We analyzed immunoglobulins (Ig) in explanted livers from SAH patients (n=45) undergoing liver transplantation and tissues from corresponding healthy donors (HD, n=10) and found massive deposition of IgG and IgA isotype antibodies associated with complement fragment C3d and C4d staining in ballooned hepatocytes in SAH livers. Ig extracted from SAH livers, but not patient serum exhibited hepatocyte killing efficacy. Employing human and Escherichia coli K12 proteome arrays, we profiled the antibodies extracted from explanted SAH, livers with other diseases, and HD livers. Compared with their counterparts extracted from livers with other diseases and HD, antibodies of IgG and IgA isotypes were highly accumulated in SAH and recognized a unique set of human proteins and E. coli antigens. Further, both Ig- and E. coli-captured Ig from SAH livers recognized common autoantigens enriched in several cellular components including cytosol and cytoplasm (IgG and IgA), nucleus, mitochondrion, and focal adhesion (IgG). Except IgM from primary biliary cholangitis livers, no common autoantigen was recognized by Ig- and E. coli-captured Ig from livers with other diseases. These findings demonstrate the presence of cross-reacting anti-bacterial IgG and IgA autoantibodies in SAH livers.

Primary renal malignant epithelioid angiomyolipoma with distant metastasis: a case report and literature review.

Epithelioid angiomyolipoma (EAML) is a rare type of mesenchymal angiomyolipoma with potential malignancy in the kidney that can cause lymph node metastases, local recurrence, and distant metastases. Herein, we describe a case of EAML in the right kidney of a 51-year-old man who was admitted to the hospital with a right abdominal mass. Computed tomography revealed a heterogeneously enhanced mass with blurred margins, which was considered a malignant tumor. A radical nephrectomy was then performed. Two years later, the patient developed liver metastases from EAML and was administered sintilimab combined with bevacizumab. The patient survived after 6 months of follow-up. Histologically, the tumors showed clear boundaries and no obvious capsules. The tumor tissue mainly consisted of epithelioid tumor cells, thick-walled blood vessels, and a small amount of adipose tissue. Tumor cells with lipid vacuoles and acinar areas were large, round, polygonal, eosinophilic, or transparent in the cytoplasm. The enlarged and hyperchromatic nuclei were accompanied by distinct nucleoli and pathological mitosis. These histopathological findings resembled those of renal cell carcinoma, and immunohistochemical analysis was performed. The tumor cells were diffusely positive for HMB45, Melan-A, CK20, vimentin antibodies, and TFE3, suggesting that the tumor originated from perivascular epithelioid cells, excluding renal cell carcinoma. The Ki-67 index was 10%. These histopathological features were observed in liver mass puncture tissues. We also summarized 46 cases of EAML with distant metastasis and explored the clinicopathological features of EAML to improve the treatment of the disease. EAML is often ignored in the clinical setting, leading to metastasis and recurrence. Therefore, EAMLs require long-term follow-up, and timely detection of recurrent disease can improve the prognosis.

Continuous renal replacement therapy with oXiris® in patients with hematologically malignant septic shock: A retrospective study.

BACKGROUND: The mortality rate from septic shock in patients with hematological malignancies (HMs) remains significantly higher than that in patients without HMs. A longer resuscitation time would definitely be harmful because of the irreversibly immunocompromised status of the patients. Shortening the resuscitation time through continuous renal replacement therapy (CRRT) with oXiris® would be an attractive strategy in managing such patients. AIM: To explore the effects of CRRT and oXiris® in shortening the resuscitation time and modifying the host response by reducing inflammation mediator levels. METHODS: Forty-five patients with HM were diagnosed with septic shock and underwent CRRT between 2018 and 2022. Patients were divided into two groups based on the hemofilter used for CRRT (oXiris® group, n = 26; M150 group, n = 19). We compared the number of days of negative and total fluid balance after 7 d of CRRT between the groups. The heart rate, norepinephrine dose, Sequential Organ Failure Assessment (SOFA) score, and blood lactic acid levels at different time points in the two groups were also compared. Blood levels of inflammatory mediators in the 26 patients in the oXiris® group were measured to further infer the possible mechanism. RESULTS: The average total fluid balance after 7 d of CRRT in the oXiris® group was significantly lower than that of patients in the M150 hemofilter group. The SOFA scores of patients after CRRT with oXiris® therapy were significantly lower than those before treatment on day 1 (d1), d3 and d7 after CRRT; these parameters were also significantly lower than those of the control group on d7. The lac level after oXiris® therapy was significantly lower than that before treatment on d3 and d7 after CRRT. There were no significant differences in the above parameters between the two groups at the other time points. In the oXiris® group, procalcitonin levels decreased on d7, whereas interleukin-6 and tumor necrosis factor levels decreased significantly on d3 and d7 after treatment. CONCLUSION: CRRT with oXiris® hemofilter may improve hemodynamics by reducing inflammatory mediators and playing a role in shortening the resuscitation period and decreasing total fluid balance in the resuscitation phases.

Resources used and trusted regarding child health information by culturally and linguistically diverse communities in Australia: An online cross-sectional survey.

BACKGROUND: Parents' play a proactive role in seeking health information to ensure optimal growth and development for their children. To date, very little is known about the differences between information seeking behaviour for child health and engagement with resources between culturally and linguistically diverse (CALD) and non-CALD parents. OBJECTIVE: To investigate the differences in resources used and trusted for information related to child health behaviours and engagement with online features among CALD and non-CALD respondents in Australia. METHODS: An analysis of a theory informed online cross-sectional survey was conducted using data from 122 CALD and 399 non-CALD parents who had a child younger than 24 months or were currently pregnant in Australia. Descriptive statistics and chi-squared were used to compare the differences, and logistic regression models were used to identify factors associated with using health resources. RESULTS: The most trusted sources for information reported by respondents were health professionals (76.2 %), websites run by health professionals (59.5 %), and government websites (53.2 %). Social media was significantly more trusted as a source of information for child health behaviours among CALD respondents than non-CALD respondents (odds ratio (OR) 1.92, P = 0.01). In contrast, booklets/ pamphlets and friends were significantly more trusted by non-CALD parents than for CALD parents (OR 0.54, P = 0.02). General search engines were used very frequently among CALD respondents for child health information (39.3 % vs 24.1 %, p = 0.013). Overall, the most common features respondents enjoyed on websites were images (81 %), videos (40.1 %), and discussion forums (39.9 %). CALD respondents significantly favoured videos (p = 0.003) while non-CALD respondents preferred obtaining information through attachments (p < 0.001). CONCLUSIONS: Despite parents' reporting health professionals, websites run by health professionals, and government websites as trustworthy, general search engines and social media were still the most frequently used information source for parents with young children. Credible resources parents deem as trustworthy should take into account effective and engaging means of disseminating information that are accessible to both CALD and non-CALD communities.

An alternative to opioid-based intravenous patient controlled analgesia in severe burn patients undergoing full thickness split graft in upper limbs.

BACKGROUND: Opioids provide good analgesic effect in burn patients during acute phase, but these patients may develop tolerance after prolonged exposure. Alternative analgesic strategies such as peripheral nerve blocks appear to provide adequate pain control while sparing opioid-related side effects. The purpose of this study was to evaluate intravenous patient-controlled analgesia (IV-PCA) and continuous peripheral nerve block (CPNB-PCA) in severe burn patients with relatively young age undergoing repeated debridement and large-area full thickness skin graft (FTSG). METHODS: The records of victims in dust explosion in Taiwan in 2016 from Chang Gung Memorial Hospital Pain Service Database between 2016 June and 2017 December were evaluated. The patients' demographic data including age, gender, weight, burn area, degree of burn, type of PCA regimen (IV-PCA versus CPNB-PCA), size of FTSG, and adverse effects were collected. RESULTS: The total in-hospital morphine consumption was significantly lower in CPNB-PCA than IV-PCA group. A trend of decrease in numerical rating scores (NRS) was observed for both groups and CPNB group had comparable NRS than IV-PCA group at rest. On movement, CPNB grouped had significantly lower NRS than IV-PCA on post-operative day 3. CONCLUSION: Our study demonstrated that in patients requiring high dosage of opioid, CPNB may be a suitable alternative for pain control.

Transcriptomes of human primary skin fibroblasts of healthy individuals reveal age-associated mRNAs and long noncoding RNAs.

Changes in the transcriptomes of human tissues with advancing age are poorly cataloged. Here, we sought to identify the coding and long noncoding RNAs present in cultured primary skin fibroblasts collected from 82 healthy individuals across a wide age spectrum (22-89 years old) who participated in the GESTALT (Genetic and Epigenetic Signatures of Translational Aging Laboratory Testing) study of the National Institute on Aging, NIH. Using high-throughput RNA sequencing and a linear regression model, we identified 1437 coding RNAs (mRNAs) and 1177 linear and circular long noncoding (lncRNAs) that were differentially abundant as a function of age. Gene set enrichment analysis (GSEA) revealed select transcription factors implicated in coordinating the transcription of subsets of differentially abundant mRNAs, while long noncoding RNA enrichment analysis (LncSEA) identified RNA-binding proteins predicted to participate in the age-associated lncRNA profiles. In summary, we report age-associated changes in the global transcriptome, coding and noncoding, from healthy human skin fibroblasts and propose that these transcripts may serve as biomarkers and therapeutic targets in aging skin.

Pregnane X receptor activation alleviates renal fibrosis in mice via interacting with p53 and inhibiting the Wnt7a/ß-catenin signaling.

Renal fibrosis is a common pathological feature of chronic kidney disease (CKD) with various etiologies, which seriously affects the structure and function of the kidney. Pregnane X receptor (PXR) is a member of the nuclear receptor superfamily and plays a critical role in regulating the genes related to xenobiotic and endobiotic metabolism in mammals. Previous studies show that PXR is expressed in the kidney and has protective effect against acute kidney injury (AKI). In this study, we investigated the role of PXR in CKD. Adenine diet-induced CKD (AD) model was established in wild-type and PXR humanized (hPXR) mice, respectively, which were treated with pregnenolone-16α-carbonitrile (PCN, 50 mg/kg, twice a week for 4 weeks) or rifampicin (RIF, 10 mg·kg-1·d-1, for 4 weeks). We showed that both PCN and RIF, which activated mouse and human PXR, respectively, improved renal function and attenuated renal fibrosis in the two types of AD mice. In addition, PCN treatment also alleviated renal fibrosis in unilateral ureter obstruction (UUO) mice. On the contrary, PXR gene deficiency exacerbated renal dysfunction and fibrosis in both adenine- and UUO-induced CKD mice. We found that PCN treatment suppressed the expression of the profibrotic Wnt7a and ß-catenin in AD mice and in cultured mouse renal tubular epithelial cells treated with TGFß1 in vitro. We demonstrated that PXR was colocalized and interacted with p53 in the nuclei of tubular epithelial cells. Overexpression of p53 increased the expression of Wnt7a, ß-catenin and its downstream gene fibronectin. We further revealed that p53 bound to the promoter of Wnt7a gene to increase its transcription and ß-catenin activation, leading to increased expression of the downstream profibrotic genes, which was inhibited by PXR. Taken together, PXR activation alleviates renal fibrosis in mice via interacting with p53 and inhibiting the Wnt7a/ß-catenin signaling pathway.

Pregnane X receptor (PXR) deficiency protects against spinal cord injury by activating NRF2/HO-1 pathway.

INTRODUCTION: As a devastating neurological disease, spinal cord injury (SCI) results in severe tissue loss and neurological dysfunction. Pregnane X receptor (PXR) is a ligand-activated nuclear receptor with a major regulatory role in xenobiotic and endobiotic metabolism and recently has been implicated in the central nervous system. In the present study, we aimed to investigate the role and mechanism of PXR in SCI. METHODS: The clip-compressive SCI model was performed in male wild-type C57BL/6 (PXR+/+ ) and PXR-knockout (PXR-/- ) mice. The N2a H2 O2 -induced injury model mimicked the pathological process of SCI in vitro. Pregnenolone 16α-carbonitrile (PCN), a mouse-specific PXR agonist, was used to activate PXR in vivo and in vitro. The siRNA was applied to knock down the PXR expression in vitro. Transcriptome sequencing analysis was performed to discover the relevant mechanism, and the NRF2 inhibitor ML385 was used to validate the involvement of PXR in influencing the NRF2/HO-1 pathway in the SCI process. RESULTS: The expression of PXR decreased after SCI and reached a minimum on the third day. In vivo, PXR knockout significantly improved the motor function of mice after SCI, meanwhile, inhibited apoptosis, inflammation, and oxidative stress induced by SCI. On the contrary, activation of PXR by PCN negatively influenced the recovery of SCI. Mechanistically, transcriptome sequencing analysis revealed that PXR activation downregulated the mRNA level of heme oxygenase-1 (HO-1) after SCI. We further verified that PXR deficiency activated the NRF2/HO-1 pathway and PXR activation inhibited this pathway in vitro. CONCLUSION: PXR is involved in the recovery of motor function after SCI by regulating NRF2/HO-1 pathway.

Targeting hypoxia-inducible factors with 32-134D safely and effectively treats diabetic eye disease in mice.

Many patients with diabetic eye disease respond inadequately to anti-VEGF therapies, implicating additional vasoactive mediators in its pathogenesis. We demonstrate that levels of angiogenic proteins regulated by HIF-1 and -2 remain elevated in the eyes of people with diabetes despite treatment with anti-VEGF therapy. Conversely, by inhibiting HIFs, we normalized the expression of multiple vasoactive mediators in mouse models of diabetic eye disease. Accumulation of HIFs and HIF-regulated vasoactive mediators in hyperglycemic animals was observed in the absence of tissue hypoxia, suggesting that targeting HIFs may be an effective early treatment for diabetic retinopathy. However, while the HIF inhibitor acriflavine prevented retinal vascular hyperpermeability in diabetic mice for several months following a single intraocular injection, accumulation of acriflavine in the retina resulted in retinal toxicity over time, raising concerns for its use in patients. Conversely, 32-134D, a recently developed HIF inhibitor structurally unrelated to acriflavine, was not toxic to the retina, yet effectively inhibited HIF accumulation and normalized HIF-regulated gene expression in mice and in human retinal organoids. Intraocular administration of 32-134D prevented retinal neovascularization and vascular hyperpermeability in mice. These results provide the foundation for clinical studies assessing 32-134D for the treatment of patients with diabetic eye disease.

Single-cell transcriptome analysis of xenotransplanted human retinal organoids defines two migratory cell populations of nonretinal origin.

Human retinal organoid transplantation could potentially be a treatment for degenerative retinal diseases. How the recipient retina regulates the survival, maturation, and proliferation of transplanted organoid cells is unknown. We transplanted human retinal organoid-derived cells into photoreceptor-deficient mice and conducted histology and single-cell RNA sequencing alongside time-matched cultured retinal organoids. Unexpectedly, we observed human cells that migrated into all recipient retinal layers and traveled long distances. Using an unbiased approach, we identified these cells as astrocytes and brain/spinal cord-like neural precursors that were absent or rare in stage-matched cultured organoids. In contrast, retinal progenitor-derived rods and cones remained in the subretinal space, maturing more rapidly than those in the cultured controls. These data suggest that recipient microenvironment promotes the maturation of transplanted photoreceptors while inducing or facilitating the survival of migratory cell populations that are not normally derived from retinal progenitors. These findings have important implications for potential cell-based treatments of retinal diseases.

Improvement of AlGaN/GaN HEMTs Linearity Using Etched-Fin Gate Structure for Ka Band Applications.

In this paper, AlGaN/GaN high electron mobility transistors (HEMTs) with etched-fin gate structures fabricated to improve device linearity for Ka-band application are reported. Within the proposed study of planar, one-etched-fin, four-etched-fin, and nine-etched-fin devices, which have 50-µm, 25-µm, 10-µm, and 5-µm partial gate widths, respectively, the four-etched-fin gate AlGaN/GaN HEMT devices have demonstrated optimized device linearity with respect to the extrinsic transconductance (Gm) value, the output third order intercept point (OIP3), and the third-order intermodulation output power (IMD3) level. The IMD3 is improved by 7 dB at 30 GHz for the 4 × 50 µm HEMT device. The OIP3 is found to reach a maximum value of 36.43 dBm with the four-etched-fin device, which exhibits high potential for the advancement of wireless power amplifier components for Ka band applications.

IKKß Inhibition Attenuates Epithelial Mesenchymal Transition of Human Stem Cell-Derived Retinal Pigment Epithelium.

Epithelial-mesenchymal transition (EMT), which is well known for its role in embryonic development, malignant transformation, and tumor progression, has also been implicated in a variety of retinal diseases, including proliferative vitreoretinopathy (PVR), age-related macular degeneration (AMD), and diabetic retinopathy. EMT of the retinal pigment epithelium (RPE), although important in the pathogenesis of these retinal conditions, is not well understood at the molecular level. We and others have shown that a variety of molecules, including the co-treatment of human stem cell-derived RPE monolayer cultures with transforming growth factor beta (TGF-ß) and the inflammatory cytokine tumor necrosis factor alpha (TNF-α), can induce RPE-EMT; however, small molecule inhibitors of RPE-EMT have been less well studied. Here, we demonstrate that BAY651942, a small molecule inhibitor of nuclear factor kapa-B kinase subunit beta (IKKß) that selectively targets NF-κB signaling, can modulate TGF-ß/TNF-α-induced RPE-EMT. Next, we performed RNA-seq studies on BAY651942 treated hRPE monolayers to dissect altered biological pathways and signaling events. Further, we validated the effect of IKKß inhibition on RPE-EMT-associated factors using a second IKKß inhibitor, BMS345541, with RPE monolayers derived from an independent stem cell line. Our data highlights the fact that pharmacological inhibition of RPE-EMT restores RPE identity and may provide a promising approach for treating retinal diseases that involve RPE dedifferentiation and EMT.