Injectable hydrogels in regeneration medicine can potentially mimic hierarchical natural living tissue and fill complexly shaped defects with minimally invasive implantation procedures. To achieve ...this goal, however, the versatile hydrogels that usually possess the nonporous structure and uncontrollable spatial agent release must overcome the difficulties in low cell‐penetrative rates of tissue regeneration. In this study, an adaptable microporous hydrogel (AMH) composed of microsized building blocks with opposite charges serves as an injectable matrix with interconnected pores and propagates gradient growth factor for spontaneous assembly into a complex shape in real time. By embedding gradient concentrations of growth factors into the building blocks, the propagated gradient of the nerve growth factor, integrated to the cell‐penetrative connected pores constructed by the building blocks in the nerve conduit, effectively promotes cell migration and induces dramatic bridging effects on peripheral nerve defects, achieving axon outgrowth of up to 4.7 mm and twofold axon fiber intensity in 4 days in vivo. Such AMHs with intrinsic properties of tunable mechanical properties, gradient propagation of biocues and effective induction of cell migration are potentially able to overcome the limitations of hydrogel‐mediated tissue regeneration in general and can possibly be used in clinical applications.
Microscale interconnected channels can be introduced in adaptable hydrogels assembled from oppositely charged building blocks, which allows propagating NGF‐gradient and cell penetration, inducing bridging effects on peripheral nerve defects.
We previously demonstrated that human pericytes, which encircle capillaries and microvessels, give rise in culture to genuine mesenchymal stem cells (MSCs). This raised the question as to whether all ...MSC are derived from pericytes. Pericytes and other cells defined on differential expression of CD34, CD31, and CD146 were sorted from the stromal vascular fraction of human white adipose tissue. Besides pericytes, CD34+ CD31- CD146- CD45- cells, which reside in the outmost layer of blood vessels, the tunica adventitia, natively expressed MSC markers and gave rise in culture to clonogenic multipotent progenitors identical to standard bone marrow-derived MSC. Despite common MSC features and developmental properties, adventitial cells and pericytes retain distinct phenotypes and genotypes through culture. However, in the presence of growth factors involved in vascular remodeling, adventitial cells acquire a pericytes-like phenotype. In conclusion, we demonstrate the co-existence of 2 separate perivascular MSC progenitors: pericytes in capillaries and microvessels and adventitial cells around larger vessels.
Summary
Reactivation of hepatitis B virus (HBV) by reverse seroconversion (HBV‐RS) after allogeneic haematopoietic stem cell transplantation (allo‐HSCT) can occur in patients with resolved HBV ...infection (rHBV, defined as negative HBV surface antigen HBsAg and positive HBV core antibody), and may cause fatal hepatitis. To explore the risk factors, we retrospectively identified 817 consecutive patients who underwent allo‐HSCT from 2005 to 2016 in this largest single centre cohort from National Taiwan Univerisity Hospital. Transplants using donors or recipients positive for HBsAg or HBV DNA were excluded, leaving 445 rHBV patients for analysis. The 3‐ and 5‐year cumulative incidence of HBV‐RS after allo‐HSCT was 8·7% and 10·5%, respectively, at a median 16 months after allo‐HSCT. All had concurrent HBV reactivation. HBV flares developed in 19% of HBV‐RS cases, but none experienced hepatic failure. Neither did it impact non‐relapse mortality or overall survival. Multivariate analysis revealed that patients with donor lacking hepatitis B surface antibody and extensive chronic graft‐versus‐host disease (cGVHD) have the highest risk for HBV‐RS, with 5‐year incidence of 24·2%. In conclusion, adoptive immunity transfer from the donor seems to have protective effects against HBV‐RS, which may alter future donor selection algorithms, and combined with extensive cGVHD provides a good target for risk‐adaptive HBV prophylaxis.
The field of next‐generation microdisplays is flourishing. Relevant display technologies, such as mini‐light emission diodes (mini‐LEDs), micro‐organic light emission diodes (micro‐OLEDs), and ...micro‐light emission diodes (micro‐LEDs) are thus in the urgent stage of development. From this perspective, comprehensive and systematical analyzes are conducted for the aforesaid microdisplay configurations. A holistic view of microdisplay technologies is developed with the corresponding performance metrics, providing a path for miscellaneous scenarios. Among these scenarios, the applications in augmented reality (AR), virtual reality (VR), wearable devices, and head‐up displays (HUD) are currently attracting considerable attention for deeper human‐digital interactions. However, there is a multiplicity of obstacles and challenges hindering such development. Nevertheless, recent advances in microdisplay technologies hold tremendous promise for the paradigms of these applications, taking a leap forward for next‐generation microdisplays. This review presents perspectives, relevant materials, and the technology landscape for such ongoing display technologies, offering guidance on the design of advanced microdisplays.
The demand for augmented reality (AR), virtual reality (VR), wearables, and head‐up display (HUD) technology has fueled the rapid growth of next‐generation microdisplays. Despite their promise, challenges remain. This review analyzes performance metrics across various scenarios and provides valuable materials and technology perspectives for ongoing display technology. Our guidance for advanced microdisplay design aims to overcome obstacles and improve the field.
Lung cancer (LC) causes the majority of cancer-related deaths. Circular RNAs (circRNAs) were reported to play roles in cancers by targeting pro- and anti-oncogenic miRNAs. However, the mechanisms of ...circRNAs in LC progression and their prognostic value of treatment response remain unclear. By using next generation sequencing (NGS) of LC cell lines’ transcriptomes, we identified highly overexpressed hsa_circ_0000190 and hsa_circ_000164 as potential biomarkers. By using the highly sensitive RT-ddPCR method, these circRNAs were shown to be secreted by cell lines and were detected in human blood. Clinical validation by RT-ddPCR was carried out on 272 (231 LC patients and 41 controls) blood samples. Higher hsa_circ_0000190 levels were associated with larger tumor size (p < 0.0001), worse histological type of adenocarcinoma (p = 0.0028), later stage (p < 0.0001), more distant metastatic organs (p = 0.0039), extrathoracic metastasis (p = 0.0004), and poor survival (p = 0.047) and prognosis. Using liquid biopsy-based RT-ddPCR, we discovered the correlation between increased hsa_circ_0000190 plasma level (p < 0.0001) and higher programmed death-ligand 1 (PD-L1) level in tumor (p = 0.0283). Notably, long-term follow-up of the immunotherapy treated cases showed that upregulated plasma hsa_circ_0000190 level correlated with poor response to systemic therapy and immunotherapy (p = 0.0002, 0.0058, respectively). Secretory circRNAs are detectable in blood by LB-based RT-ddPCR and may serve as blood-based biomarkers to monitor disease progression and treatment efficacy.
We have identified vascular pericytes in multiple human organs on expression of CD146, NG2, PDGF‐Rβ, and mesenchymal stem cell markers (CD44, CD73, CD90, CD105) and absence of blood, endothelial, and ...myogenic cell markers. Pericytes purified from all tissues were myogenic in culture and in vivo, sustained long‐term culture during which they expressed markers of mesenchymal stem cells, and exhibited, at the clonal level, osteogenic, chondrogenic, and adipogenic potentials. These results suggest that human capillary and microvessel walls all over the organism harbor a reserve of progenitor cells that are at the origin of the elusive mesenchymal stem cells, so far identified only retrospectively in primary tissue cultures.
Long non-coding RNAs (lncRNAs) represent the majority of cellular transcripts and play pivotal roles in hematopoiesis. However, their clinical relevance in acute myeloid leukemia (AML) and ...myelodysplastic syndrome (MDS) remains largely unknown. Here, we investigated the functions of HOXB-AS3, a lncRNA located at human HOXB cluster, in the myeloid cells, and analyzed the prognostic significances in patients with AML and MDS.
shRNAs were used to downregulate HOXB-AS3 in the cell lines and the effect was evaluated by quantitative polymerase chain reaction. The proliferation of the cell lines was illustrated by proliferation and BrdU flow assays. Further, we retrospectively analyzed the HOXB-AS3 expression in 193 patients with AML and 157 with MDS by microarray analysis, and evaluated its clinical importance.
Downregulation of HOXB-AS3 suppressed cell proliferation. Mechanistically, HOXB-AS3 potentiated the expressions of several key factors in cell cycle progression and DNA replication without affecting the expressions of HOX genes. In AML, patients with higher HOXB-AS3 expression had shorter survival than those with lower HOXB-AS3 expression (median overall survival (OS), 17.7 months versus not reached, P < 0.0001; median relapse-free survival, 12.9 months versus not reached, P = 0.0070). In MDS, patients with higher HOXB-AS3 expression also had adverse prognosis compared with those with lower HOXB-AS3 expression (median OS, 14.6 months versus 42.4 months, P = 0.0018). The prognostic significance of HOXB-AS3 expression was validated in the TCGA AML cohort and another MDS cohort from our institute. The subgroup analyses in MDS patients showed that higher HOXB-AS3 expressions could predict poor prognosis only in lower-risk (median OS, 29.2 months versus 77.3 months, P = 0.0194), but not higher-risk group.
This study uncovers a promoting role of HOXB-AS3 in myeloid malignancies and identifies the prognostic value of HOXB-AS3 expression in AML and MDS patients, particularly in the lower-risk group.
Initial symptoms of dengue fever are non-specific, and thus definite diagnosis requires laboratory confirmation. Detection of IgM against dengue virus (DENV) has become widely used for dengue ...diagnosis. Understanding the persistence of anti-DENV IgM in subjects after acute infection is essential in order to interpret test results correctly. Although the longevity of anti-DENV IgM has been vehemently investigated in symptomatic children, anti-DENV IgM persistence in adults and in asymptomatically infected people have seldom been reported.
We prospectively investigated 44 adults with detectable anti-DENV IgM in a serosurvey conducted in the 2015 dengue epidemic in Tainan, Taiwan. Among subjects within the cohort, 17 were classified to be symptomatic and 27 were asymptomatic. The enzyme-linked immunosorbent assay (ELISA) from Standard Diagnostic (SD) and Focus Diagnostic were used to detect anti-DENV IgM for specimens collected initially, at 6 and 12 months. Regression analyses were used to estimate the duration of anti-DENV IgM fell below the detectable level. Rapid dengue tests from Standard Diagnostics had been widely adopted to detect anti-DENV IgM in Taiwan during the 2015 dengue outbreak. As such, collected specimens were also evaluated with the SD rapid dengue test in parallel.
Anti-DENV IgM was detectable in 70.5 and 46.2% of the 44 subjects at 6 months and 12 months by the SD ELISA, respectively, while 13.6 and 7.7%, respectively, by the Focus ELISA. There was no significant difference in anti-DENV IgM detection for the follow-up specimens between subjects with symptomatic and asymptomatic infections. The regression analysis estimated that anti-DENV IgM persistence fell to the undetectable level at 338.3 days (95% CI 279.7-446.9) by SD ELISA, while at 175.7 days (95% CI 121.9-221.1) by Focus ELISA. The detectable frequency of anti-DENV IgM by rapid tests was 86.4%, 68.2 and 35.9% at initial, 6 and 12 months, respectively.
Anti-DENV IgM was found to persist much longer than previously thought, suggesting a necessity of re-evaluation of the use of anti-DENV IgM for both the diagnosis of dengue and serological surveillance, especially when large outbreaks have occurred in the preceding year.
The phosphor‐converted light‐emitting diode (PC‐LED) has become an indispensable solid‐state lighting and display technologies in the modern society. Nevertheless, the use of scarce rare‐earth ...elements and the thermal quenching (TQ) behavior are still two most crucial issues yet to be solved. Here, this work successfully demonstrates a highly efficient and thermally stable green emissive MnI2(XanPO) crystals showing a notable photoluminescence quantum yield (PLQY) of 94% and a super TQ resistance from 4 to 623 K. This unprecedented superior thermal stability is attributed to the low electron–phonon coupling and the unique rigid crystal structure of MnI2(XanPO) over the whole temperature range based on the temperature‐dependent photoluminescence (PL) and single crystal X‐ray diffraction (SCXRD) analyses. Considering these appealing properties, green PC‐LEDs with a power efficacy of 102.5 lm W−1, an external quantum efficiency (EQE) of 22.7% and a peak luminance up to 7750 000 cd m−2 are fabricated by integrating MnI2(XanPO) with commercial blue LEDs. Moreover, the applicability of MnI2(XanPO) in both micro‐LEDs and organic light‐emitting diodes (OLEDs) is also demonstrated. In a nutshell, this study uncovers a candidate of highly luminescent and TQ resistant manganese halide suitable for a variety of emission applications.
A highly efficient and thermally stable manganese halide crystal, MnI2(XanPO) is demonstrated. The low electron–phono coupling along with rigid crystal structure contributes to excellent photoluminescent quantum yield of 94% with unprecedented near zero thermal quenching from 4 to 623 K. The crystals find their applications in light emitting diodes and micro light emitting diodes with excellent external quantum efficiency (EQE) up to 22.7% and power efficacy as high as 102.5 lm W−1.
PDF
