Optimized strategies of cloud droplet distribution retrieval using satellite multi-directional polarimetric optical measurements: information content approach.

Multi-directional polarized optical sensors are increasingly vital in passive remote sensing, deepening our understanding of global cloud properties. Nevertheless, uncertainty lingers on how these observations can contribute to our knowledge of cloud diversity. The variability in cloud PSD (Particle Size Distribution) significantly influences a wide array of cloud characteristics, while unidentified factors in RT (Radiative Transfer) may introduce errors into the cloud PSD retrieval algorithm. Therefore, establishing unified evaluation criteria for both optical device configuration and inversion methods is crucial. Our study, based on Bayesian theory and RT, assesses the information content of both cloud effective radius and effective variance retrieval, along with the key factors affecting their retrieval in multi-directional polarized observations, using the calculation of DFS (Degree of Freedom for Signals).We consider the process of solar incidence, cloud scattering, and sensor reception, and discuss the impact of various sensor configurations, cloud characteristics, and other components on the retrieval of cloud PSD. Correspondingly, we observed a 48% improvement in the information content of cloud PSD with the incorporation of multi-directional polarized measurements in the rainbow region. Cloud droplet concentration significantly influences inversion, but its PSD does not cause monotonic linear interference on information content. The blending of particle mixtures with different PSD has a significant negative impact on DFS. In cases where the AOD (Aerosol Optical Depth) is less than 0.5 and the COT (Cloud Optical Thickness) exceeds 5, the influence of aerosol and surface contributions on inversion can be neglected. Our findings would serve as a foundation for future instrument design improvements and enhancements to retrieval algorithms.

The causal relationship between autoimmune thyroid disorders and telomere length: A Mendelian randomization and colocalization study.

This study aimed to evaluate whether there is a causal relationship between autoimmune thyroid disorders (AITDs) and telomere length (TL) in the European population and whether there is reverse causality. In this study, Mendelian randomization (MR) and colocalization analysis were conducted to assess the potential causal relationship between AITDs and TL using summary statistics from large-scale genome-wide association studies, followed by analysis of the relationship between TL and thyroid stimulating hormone and free thyroxine (FT4) to help interpret the findings. The inverse variance weighted (IVW) method was used to estimate the causal estimates. The weighted median, MR-Egger and leave-one-out methods were used as sensitivity analyses. The IVW method results showed a significant causal relationship between autoimmune hyperthyroidism and TL (ß = -1.93 × 10-2 ; p = 4.54 × 10-5 ). There was no causal relationship between autoimmune hypothyroidism and TL (ß = -3.99 × 10-3 ; p = 0.324). The results of the reverse MR analysis showed that genetically TL had a significant causal relationship on autoimmune hyperthyroidism (IVW: odds ratio (OR) = 0.49; p = 2.83 × 10-4 ) and autoimmune hypothyroidism (IVW: OR = 0.86; p = 7.46 × 10-3 ). Both horizontal pleiotropy and heterogeneity tests indicated the validity of our bidirectional MR study. Finally, colocalization analysis suggested that there were shared causal variants between autoimmune hyperthyroidism and TL, further highlighting the robustness of the results. In conclusion, autoimmune hyperthyroidism may accelerate telomere attrition, and telomere attrition is a causal factor for AITDs.

High sensitivity distributed dynamic pressure sensor based on dual-linear frequency modulated optical frequency domain reflectometry.

In this Letter, we propose and experimentally demonstrate a highly sensitive distributed dynamic pressure sensor based on a dual-linear frequency modulated optical frequency domain reflectometry (OFDR) and a coating thickness-enhanced single-mode fiber (SMF). A dual-sideband linear frequency modulation (LFM) signal is used to interrogate the sensing fiber, which allows us to obtain a dual-sideband Rayleigh backscattering signal. Due to the opposite slopes of the two LFM sidebands, the Rayleigh backscattering spectra of the two sidebands drift in opposite directions when the fiber is disturbed. By subtracting the frequency shifts of the two spectra, we can double the system's sensitivity. We further enhance the sensitivity by using an SMF with a coating thickness of 200 µm. This results in a pressure sensitivity of 3979 MHz/MPa, a measurement accuracy of 0.76 kPa, and a spatial resolution of 35 cm over a 500 m optical fiber. Our system successfully detected a dynamic pressure change at a sampling rate of 1.25 kHz, demonstrating the sensor's excellent dynamic measuring capabilities.

Noninvasive Isocitrate Dehydrogenase 1 Status Prediction in Grade II/III Glioma Based on Magnetic Resonance Images: A Transfer Learning Strategy.

OBJECTIVE: The aim of this study was to evaluate transfer learning combined with various convolutional neural networks (TL-CNNs) in predicting isocitrate dehydrogenase 1 ( IDH1 ) status of grade II/III gliomas. METHODS: Grade II/III glioma patients diagnosed at the Tangdu Hospital (August 2009 to May 2017) were retrospectively enrolled, including 54 patients with IDH1 mutant and 56 patients with wild-type IDH1 . Convolutional neural networks, AlexNet, GoogLeNet, ResNet, and VGGNet were fine-tuned with T2-weighted imaging (T2WI), fluid attenuation inversion recovery (FLAIR), and contrast-enhanced T1-weighted imaging (T1CE) images. The single-modal networks were integrated with averaged sigmoid probabilities, logistic regression, and support vector machine. FLAIR-T1CE-fusion (FC-fusion), T2WI-T1CE-fusion (TC-fusion), and FLAIR-T2WI-T1CE-fusion (FTC-fusion) were used for fine-tuning TL-CNNs. RESULTS: IDH1 -mutant prediction accuracies using AlexNet, GoogLeNet, ResNet, and VGGNet achieved 70.0% (AUC = 0.660), 65.0% (AUC = 0.600), 70.0% (AUC = 0.700), and 80.0% (AUC = 0.730) for T2WI images, 70.0% (AUC = 0.660), 70.0% (AUC = 0.620), 70.0% (AUC = 0.710), and 80.0% (AUC = 0.720) for FLAIR images, and 73.7% (AUC = 0.744), 73.7% (AUC = 0.656), 73.7% (AUC = 0.633), and 73.7% (AUC = 0.700) for T1CE images, respectively. The highest AUC (0.800) was achieved using VGGNet and FC-fusion images. CONCLUSIONS: TL-CNNs (especially VGGNet) had a potential predictive value for IDH1 -mutant status of grade II/III gliomas.

Coherent OTDR with large dynamic range based on double-sideband linear frequency modulation pulse.

Rayleigh scattering-based distributed optical fiber sensors with long sensing distance and large dynamic range are highly desired for application scenarios such as vehicle tracking, structure health monitoring, and geological survey. To enlarge the dynamic range, we propose a coherent optical time domain reflectometry (COTDR) based on double-sideband linear frequency modulation (LFM) pulse. By utilizing I/Q demodulation, both the positive and negative frequency band of the Rayleigh backscattering (RBS) signal can be properly demodulated. Consequently, the dynamic range is doubled without increasing the bandwidth of signal generator, photodetector (PD), and oscilloscope. In the experiment, the chirped pulse with 10 µs pulse width and 498 MHz frequency sweeping range is launched into the sensing fiber. Single-shot strain measurement is achieved over 5 km single-mode fiber with a spatial resolution of 2.5 m and a strain sensitivity of 7.5 pε/H z. A vibration signal with 3.09 µÎµ peak-to-peak amplitude (corresponding to 461 MHz frequency shift) is successfully measured with the double-sideband spectrum, which cannot be properly recovered with the single-sideband spectrum.

Measures of explained variation under the mixture cure model for survival data.

Explained variation is well understood under linear regression models and has been extended to models for survival data. In this article, we consider the mixture cure models. We propose two approaches to define explained variation under the mixture cure models, one based on the Kullback-Leibler information gain and the other based on residual sum of squares. We show that the proposed measures have desired properties as measures of explained variation, similar to those under other regression models. A simulation study is conducted to demonstrate the properties of the proposed measures. They are also applied to real data analyses to illustrate the use of explained variation.

Serine-arginine splicing factor 2 promotes oesophageal cancer progression by regulating alternative splicing of interferon regulatory factor 3.

OBJECTIVE: Often, alternative splicing is used by cancer cells to produce or increase proteins that promote growth and survival through alternative splicing. Although RNA-binding proteins are known to regulate alternative splicing events associated with tumorigenesis, their role in oesophageal cancer (EC) has rarely been explored. METHODS: We analysed the expression pattern of several relatively well characterized splicing regulators on 183 samples from TCGA cohort of oesophageal cancer; the effectiveness of the knockdown of SRSF2 was subsequently verified by immunoblotting; we measured the ability of cells treated with lenti-sh-SRSF2/lenti-sh2-SRSF2 to invade through an extracellular matrix coating by transwell invasion assay; using RNA-seq data to identify its potential target genes; we performed qRT-PCR to detect the changes of exon 2 usage in lenti-sh-SRSF2 transduced KYSE30 cells to determine the possible effect of SRSF2 on splicing regulation of IRF3; RNA Electrophoretic mobility shift assay (RNA-EMSA) was performed by the incubation of purified SRSF2 protein and biotinylated RNA probes; we performed luciferase assay to confirm the effect of SRSF2 on IFN1 promoter activity. RESULTS: We found upregulation of SRSF2 is correlated with the development of EC; Knock-down of SRSF2 inhibits EC cell proliferation, migration, and invasion; SRSF2 regulates the splicing pattern of IRF3 in EC cells; SRSF2 interacts with exon 2 of IRF3 to regulate its exclusion; SRSF2 inhibits the transcription of IFN1 in EC cells. CONCLUSION: This study identified a novel regulatory axis involved in EC from the various aspects of splicing regulation.

High-sensitivity distributed relative salinity sensor based on frequency-scanning φ-OTDR.

In this paper, a high-sensitivity distributed optical fiber salinity sensor based on frequency-scanning phase-sensitive optical time-domain reflectometry (φ-OTDR) and polyimide-coated single-mode fiber is proposed. Distributed salinity sensing over an 1100 m polyimide-coated fiber with a 1 m spatial resolution was demonstrated, and a sensitivity of 782.4 MHz/(mol/L) was achieved with the salinity changing from 0 mol/L to 1.61 mol/L. Then the measurement accuracies of frequency shift and salinity were evaluated theoretically and experimentally. Both theoretical and experimental results show that the measurement accuracy deteriorates as the pulse width decreases, resulting in a trade-off between the spatial resolution and measurement accuracy. The measurement uncertainty of salinity is 0.022 mol/L in the case of 30 cm spatial resolution. And when the spatial resolution is set to be 2 m, the measurement uncertainty of salinity decreases to 0.005 mol/L. The response time of the fiber to external salinity change has also been investigated, and it takes about 8 minutes for the fiber to reach a stable state. The proposed salinity sensor exhibits high sensitivity and long measurement range, which may be used for distributed marine environmental monitoring.

Life-threatening hemoptysis accompanied by internal thoracic artery aneurysms in a 28-year-old perinatal woman: a case report.

BACKGROUND: Life-threatening hemoptysis presents an immediate diagnostic and therapeutic challenge, especially during the perinatal period. CASE PRESENTATION: A 28-year-old perinatal woman with no significant past medical or surgical history presented with repeating hemoptysis and respiratory failure. Computed tomography revealed a 2.1 × 3.2  cm2 inhomogeneous tumorous lesion in the right superior mediastinum and a right main bronchus obstruction along with atelectasis of the right lung. Bronchoscopy showed a tumorous protrusion blocking the right main bronchus with active hemorrhage, and malignancy was suspected. Bronchial artery embolization (BAE) was performed to control the bleeding. The arteriogram revealed tortuosity, dilation and hypertrophy of the right bronchial arteries and aneurysms of the internal thoracic artery (ITA). The bleeding completely stopped after BAE. Bronchoscopy was performed again to remove residual blood clots. The patient recovered soon after the procedure and was discharged. CONCLUSIONS: Life-threatening hemoptysis concomitant with ITA aneurysms, which may have a misleading clinical diagnosis and treatment options, has not been reported previously in perinatal women. BAE could be used as a first-line treatment irrespective of the underlying causes.

Ten years of China's new healthcare reform: a longitudinal study on changes in health resources.

BACKGROUND: China launched a new round of healthcare-system reform in 2009 and proposed the goal of equal and guaranteed essential medical and health services for all by 2020. We aimed to investigate the changes in China's health resources over the past ten years after the healthcare reform. METHODS: Data were collected from the China Statistical Yearbook and China Health Statistics Yearbook from 2009 to 2018. Four categories and ten indicators of health resources were analyzed. A descriptive analysis was used to present the overall condition. The Health Resource Density Index was applied to showcase health-resource distribution in demographic and geographic dimensions. The global and local Moran's I were used to assess the spatial autocorrelation of health resources. Concentration Index (CI) was used to quantify the equity of health-resource distribution. A Geo-Detector model and Geographic Weighted Regression (GWR) were applied to assess the association between gross domestic product (GDP) per capita and health resources. RESULTS: Health resources have increased over the past ten years. The global and local Moran's I suggested spatial aggregation in the distribution of health resources. Hospital beds were concentrated in wealthier areas, but this inequity decreased yearly (from CI=0.0587 in 2009 to CI=0.0021 in 2018). Primary medical and health institutions (PMHI) and their beds were concentrated in poorer areas (CI remained negative). Healthcare employees were concentrated in wealthier areas (CI remained positive). In 2017, the q-statistics indicated that the explanatory power of GDP per capita to beds, health personnel, and health expenditure was 40.7%, 50.3%, and 42.5%, respectively. The coefficients of GWR remained positive with statistical significance, indicating the positive association between GDP per capita and health resources. CONCLUSIONS: From 2009 to 2018, the total amount of health resources in China has increased substantially. Spatial aggregation existed in the health-resources distribution. Health resources tended to be concentrated in wealthier areas. When allocating health resources, the governments should take economic factors into account.

Invasion and Colonization Pattern of Fusarium fujikuroi in Rice.

Bakanae disease in rice can cause abnormal elongation of the stem and leaves, development of adventitious roots, a larger leaf angle, and even death. Little is known about the infection, colonization, and distribution of Fusarium fujikuroi in rice plants across different growth stages. In this study, microscopic observation and quantitative real-time PCR were combined to investigate the pathogenesis of bakanae, using artificially inoculated seedlings of a susceptible rice cultivar, Zerawchanica karatals (ZK), a resistant cultivar, Tainung 67 (TNG67), naturally infected adult field plants (cultivars Kaohsiung 139, Taikeng 2, and Tainan 11), and an F. fujikuroi isolate expressing green fluorescent protein. In rice seedlings, F. fujikuroi hyphae were found to directly penetrate the epidermis of basal stems and roots, then extend inter- and intracellularly to invade the vascular bundles. Occlusion of vascular bundles and radial hyphal expansion from vascular bundles to surrounding parenchyma were observed in adult plants. Analysis of consecutive 3-cm segments of the whole plant revealed that F. fujikuroi was largely confined to the embryo, basal stem, and basal roots in seedlings, and distributed unevenly in the lower aerial parts (including nodes and internodes) of adult plants. The elongation and development of adventitious roots did not necessarily correlate with the amount of F. fujikuroi in diseased plants. Treatment of rice seeds with gibberellic acid-3 (GA3) at 0.5 mg/liter resulted in significantly more elongation of ZK than TNG67 seedlings, suggesting that the susceptibility of ZK to bakanae is associated with its higher sensitivity to GA3.

Adult-onset SMALED2 due to a novel BICD2 mutation presenting with asymmetrical lower limb involvement.

Heterozygous variants in the bicaudal D homolog 2 gene (BICD2) are associated with autosomal dominant spinal muscular atrophy with lower extremity predominance (SMALED2). This disease is usually characterized by congenital or early-onset muscle weakness and atrophy of the lower extremities with benign or slow progression. We herein described an autosomal dominant inherited pedigree with SMALED2 in which the affected individuals presented with late adult-onset muscle weakness and wasting in the lower extremities. Obviously asymmetrical involvement of the lower limbs was observed in 3 individuals. Muscle magnetic resonance imaging revealed considerable fatty infiltrations in the middle compartment of the lower legs, including the soleus and tibialis posterior muscles. Muscle biopsy samples displayed a neurogenic pattern, but some chronic myopathy-like features were also observed. A novel heterozygous missense mutation (c.361C>G) was identified in a highly-conserved motif of BICD2. Patients with SMALED2 can present with late adult-onset and asymmetrical involvement of the lower limbs. The present study expands the clinical and mutational spectrum of SMALED2.

Betacellulin regulates the proliferation and differentiation of retinal progenitor cells in vitro.

Retinal progenitor cells (RPCs) hold great potential for the treatment of retinal degenerative diseases. However, their proliferation capacity and differentiation potential towards specific retinal neurons are limited, which limit their future clinical applications. Thus, it is important to improve the RPCs' ability to proliferate and differentiate. Currently, epidermal growth factor (EGF) is commonly used to stimulate RPC growth in vitro. In this study, we find that betacellulin (BTC), a member of the EGF family, plays important roles in the proliferation and differentiation of RPCs. Our results showed that BTC can significantly promote the proliferation of RPCs more efficiently than EGF. EGF stimulated RPC proliferation through the EGFR/ErbB2-Erk pathway, while BTC stimulated RPC proliferation more powerfully through the EGFR/ErbB2/ErbB4-Akt/Erk pathway. Meanwhile, under differentiated conditions, the BTC-pre-treated RPCs were preferentially differentiated into retinal neurons, including photoreceptors, one of the most important types of cells for retinal cell replacement therapy, compared to the EGF-pre-treated RPCs. In addition, knockdown of endogenous BTC expression can also obviously promote RPC differentiation into retinal neuronal cells. This data demonstrate that BTC plays important roles in promoting RPC proliferation and differentiation into retinal neurons. This study may provide new insights into the study of RPC proliferation and differentiation and make a step towards the application of RPCs in the treatment of retinal degenerative diseases.

Decellularized matrix of adipose-derived mesenchymal stromal cells enhanced retinal progenitor cell proliferation via the Akt/Erk pathway and neuronal differentiation.

BACKGROUND AIMS: Retinal progenitor cells (RPCs) are a promising cell therapy treatment for retinal degenerative diseases. However, problems with limited proliferation ability and differentiation preference toward glia rather than neurons restrict the clinical application of these RPCs. The extracellular matrix (ECM) has been recognized to provide an appropriate microenvironment to support stem cell adhesion and direct cell behaviors, such as self-renewal and differentiation. METHODS: In this study, decellularized matrix of adipose-derived mesenchymal stromal cells (DMA) was manufactured using a chemical agent method (0.5% ammonium hydroxide Triton + 20 mmol/L NH4OH) in combination with a biological agent method (DNase solution), and the resulting DMA were evaluated by scanning electron microscopy (SEM) and immunocytochemistry. The effect of DMA on RPC proliferation and differentiation was evaluated by quantitative polymerase chain reaction, Western blot and immunocytochemistry analysis. RESULTS: DMA was successfully fabricated, as demonstrated by SEM and immunocytochemistry. Compared with tissue culture plates, DMA may effectively enhance the proliferation of RPCs by activating Akt and Erk phosphorylation; when the two pathways were blocked, the promoting effect was reversed. Moreover, DMA promoted the differentiation of RPCs toward retinal neurons, especially rhodopsin- and recoverin-positive photoreceptors, which is the most interesting class of cells for retinal degeneration treatment. CONCLUSIONS: These results indicate that DMA has important roles in governing RPC proliferation and differentiation and may contribute to the application of RPCs in treating retinal degenerative diseases.

Acute-onset multiple acyl-CoA dehydrogenase deficiency mimicking Guillain-Barré syndrome: two cases report.

BACKGROUND: Multiple acyl-CoA dehydrogenase deficiency (MADD) showed great clinical heterogeneity and poses a challenge to diagnosis. Guillain-Barré syndrome (GBS) is an acute-onset autoimmune-mediated peripheral neuropathy. However, no patients of acute-onset MADD mimicking the GBS phenotype are reported previously. CASE PRESENTATION: Two patients displayed acute-onset limb weakness, areflexia, and length-dependent sensory disturbances, which clinically indicate the diagnosis of GBS, but electrophysiological and cerebrospinal fluid results threw doubtful points to the initial diagnosis. The muscle biopsy showed lipid storage disorder; and compound heterozygous mutations in the electron transfer flavoprotein dehydrogenase (ETFDH) gene were found in the two patients through targeted next generation sequencing, which provided the definite diagnostic evidences of late-onset MADD. Muscle weakness was quickly improved by riboflavin supplementation, but sensory disturbances required a long-term treatment. DISCUSSION: The present two cases have demonstrated that MADD can mimic GBS. Taking into consideration the significant differences of therapeutic regimen and prognosis, MADD should be included in the differential diagnosis of GBS.

Novel ABCD1 Gene Mutation in Adrenomyeloneuropathy with Hypoplasia and Agenesis of the Corpus Callosum.

BACKGROUND: Adult adrenomyeloneuropathy (AMN) is caused by mutations in the ABCD1 gene. Some pure AMN patients develop cerebral demyelination late in life. However, hypoplasia and agenesis of the corpus callosum (CC) has never been reported in AMN patients. OBJECTIVE: To describe a new clinical variant of AMN that is possibly caused by a novel ABCD1 gene mutation. METHODS: A total of 10 members in an X-linked inherited family were examined. The age at onset, progression of disability, and clinical manifestations were collected. Blood tests of the index case were conducted in an academic hospital. Cerebral and spinal MRI was performed in 4 affected members using a Siemens 3.0-T or Hitachi 1.0-T MR scanner. Whole-exome sequencing was conducted in the index case, which was subsequently validated by Sanger sequencing in the family. RESULTS: The patients displayed typical degenerative spastic paraparesis and peripheral sensorimotor neuropathy with some intrafamilial variations. In addition to neurological deficits, all male patients displayed alopecia since adolescence. Furthermore, an increase in plasma long-chain fatty acids was observed. Based on these presentations, adult AMN was diagnosed for the patients. Intriguingly, cerebral MRI showed multiple types of hypoplasia and agenesis of the CC including anterior remnant CC agenesis, truncated corpus and splenium, anterior remnant CC agenesis along with thin corpus and splenium. Whole-exome sequencing revealed a nonsense mutation (c.231G>A) which results in a truncated protein product (p.W77X) that might be nonfunctional. No other mutations associated with alopecia or hypoplasia and agenesis of the CC were identified in the exome-sequencing database. CONCLUSION: In addition to the typical symptoms such as spastic myelopathy, cognitive impairment, mixed neuropathy, and alopecia, AMN patients can also display hypoplasia and agenesis of the CC, which was not described in the other AMN patients reported before.

[Effect of SRC Kinase on Adriamycin Resistance and Invasion and Metastasis in Human Breast Cancer Cells].

OBJECTIVE: To investigate the role of SRC kinase inhibitor PP2 in drug resistance to adriamycin (ADM) in breast cancer cells and invasion, metastasis of cells. METHODS: MTT assay was used to detect the inhibitory effect of ADM on MCF-7 and MCF-7/ADM cells. The 50% inhibitory concentration (IC50) and resistance index (RI) of cells were calculated. The expression of MDR1, connexin 43 (Cx43) and SRC proteins in breast cancer cells were detected by Western blot assay. Transwell experiment and cell scratch test were used to determine the invasion and migration of cells respectively [MCF-7, MCF-7/ADM, PP2 (1, 2, 4 µmol/L)]. Standard colony formation assay was used to detect the cytotoxicity effect of 4 µmol/L PP2 pretreatment on ADM. RESULTS: ADM inhibited the proliferation of MCF-7 more than MCF-7/ADM cells (P<0.01). The IC50 of MCF-7/ADM cells was 24.55 µmol/L, the IC50 of MCF-7/ADM cells was 770.57 µmol/L, the RI was 31. Compared with MCF-7 cells, expressions of the multidrug resistance proteins MDR1 and SRC were significantly increased (P<0.01). The invasion and migration ability of the MCF-7/ADM cells was stronger than that of the sensitive cells (P<0.01). When MCF-7/ADM was exposed to SRC inhibitor PP2, the invasion and metastasis ability of cells were inhibited (P<0.01) and the rate of colony formation was decreased, that is, more sensitivity to ADM (P<0.01). CONCLUSION: The resistance of MCF-7 to ADM is accompanied by increased expression of SRC. SRC inhibitor PP2 can reduce the cell resistance, ability of invasion and metastasis.

Progress of stem/progenitor cell-based therapy for retinal degeneration.

Retinal degeneration (RD), such as age-related macular degeneration (AMD) and retinitis pigmentosa, is one of the leading causes of blindness. Presently, no satisfactory therapeutic options are available for these diseases principally because the retina and retinal pigmented epithelium (RPE) do not regenerate, although wet AMD can be prevented from further progression by anti-vascular endothelial growth factor therapy. Nevertheless, stem/progenitor cell approaches exhibit enormous potential for RD treatment using strategies mainly aimed at the rescue and replacement of photoreceptors and RPE. The sources of stem/progenitor cells are classified into two broad categories in this review, which are (1) ocular-derived progenitor cells, such as retinal progenitor cells, and (2) non-ocular-derived stem cells, including embryonic stem cells, induced pluripotent stem cells, and mesenchymal stromal cells. Here, we discuss in detail the progress in the study of four predominant stem/progenitor cell types used in animal models of RD. A short overview of clinical trials involving the stem/progenitor cells is also presented. Currently, stem/progenitor cell therapies for RD still have some drawbacks such as inhibited proliferation and/or differentiation in vitro (with the exception of the RPE) and limited long-term survival and function of grafts in vivo. Despite these challenges, stem/progenitor cells represent the most promising strategy for RD treatment in the near future.

Comprehensive analysis of disulfidptosis-related lncRNAs for predicting prognosis and response of immunotherapy in pancreatic adenocarcinoma.

Background: Pancreatic adenocarcinoma (PAAD) is a common and deadly tumor. Currently, there is a severe lack of therapeutic options. As a novel mode of cell death, increasing evidence reveals the important role of the disulfidptosis in cancer. However, few studies have utilized disulfidptosis-related long-stranded non-coding RNAs (DRlncRNAs) to investigate the prognosis of PAAD. Methods: We comprehensively analyzed the expression and prognostic value of 958 DRlncRNAs in PAAD using data from The Cancer Genome Atlas (TCGA). We established and validated a new DRlncRNAs-related prognostic index by least absolute shrinkage and selection operator (LASSO) and COX regression analysis. In addition, we built a nomogram consisting of risk score, age, gender, tumor grade and stage to validate the clinical feasibility of the index. We further evaluated the value of the index in terms of PAAD functional pathways, tumor microenvironment (TME) and tumor mutations. Results: We designed a risk model for five DRlncRNAs and demonstrated its accuracy using receiver operating characteristic (ROC) curves. COX regression suggested that the model may be an independent predictor of cancer prognosis. Tumor immune infiltration analysis revealed that low-risk subgroups had higher extent of immune infiltration, higher sensitivity to immunotherapy and a higher TME score. This is helpful for us to discover more precise immunotherapy for PAAD patients. Conclusions: In conclusion, we established a DRlncRNA index comprising of five DRlncRNAs, which may provide new insights for clinical diagnosis and precision therapy.

Research progress of the inferior colliculus: from Neuron, neural circuit to auditory disease.

The auditory midbrain, also known as the inferior colliculus (IC), serves as a crucial hub in the auditory pathway. Comprising diverse cell types, the IC plays a pivotal role in various auditory functions, including sound localization, auditory plasticity, sound detection, and sound-induced behaviors. Notably, the IC is implicated in several auditory central disorders, such as tinnitus, age-related hearing loss, autism and Fragile X syndrome. Accurate classification of IC neurons is vital for comprehending both normal and dysfunctional aspects of IC function. Various parameters, including dendritic morphology, neurotransmitter synthesis, potassium currents, biomarkers, and axonal targets, have been employed to identify distinct neuron types within the IC. However, the challenge persists in effectively classifying IC neurons into functional categories due to the limited clustering capabilities of most parameters. Recent studies utilizing advanced neuroscience technologies have begun to shed light on biomarker-based approaches in the IC, providing insights into specific cellular properties and offering a potential avenue for understanding IC functions. This review focuses on recent advancements in IC research, spanning from neurons and neural circuits to aspects related to auditory diseases.