First telomere-to-telomere gapless assembly of the rice blast fungus Pyricularia oryzae.

Rice blast caused by Pyricularia oryzae (syn., Magnaporthe oryzae) was one of the most destructive diseases of rice throughout the world. Genome assembly was fundamental to genetic variation identification and critically impacted the understanding of its ability to overcome host resistance. Here, we report a gapless genome assembly of rice blast fungus P. oryzae strain P131 using PacBio, Illumina and high throughput chromatin conformation capture (Hi-C) sequencing data. This assembly contained seven complete chromosomes (43,237,743 bp) and a circular mitochondrial genome (34,866 bp). Approximately 14.31% of this assembly carried repeat sequences, significantly greater than its previous assembled version. This assembly had a 99.9% complement in BUSCO evaluation. A total of 14,982 genes protein-coding genes were predicted. In summary, we assembled the first telomere-to-telomere gapless genome of P. oryzae, which would be a valuable genome resource for future research on the genome evolution and host adaptation.

NUP85 alleviates lipid metabolism and inflammation by regulating PI3K/AKT signaling pathway in nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is one of the common causes of chronic liver disease in the world. The problem of NAFLD had become increasingly prominent. However, its pathogenesis is still indistinct. As we all know, NAFLD begins with the accumulation of triglyceride (TG), leading to fatty degeneration, inflammation and other liver tissues damage. Notably, structure of nucleoporin 85 (NUP85) is related to lipid metabolism and inflammation of liver diseases. In this study, the results of researches indicated that NUP85 played a critical role in NAFLD. Firstly, the expression level of NUP85 in methionine-choline-deficient (MCD)-induced mice increased distinctly, as well as the levels of fat disorder and inflammation. On the contrary, knockdown of NUP85 had the opposite effects. In vitro, AML-12 cells were stimulated with 2 mm free fatty acids (FFA) for 24 h. Results also proved that NUP85 significantly increased in model group, and increased lipid accumulation and inflammation level. Besides, NUP85 protein could interact with C-C motif chemokine receptor 2 (CCR2). Furthermore, when NUP85 protein expressed at an extremely low level, the expression level of CCR2 protein also decreased, accompanied with an inhibition of phosphorylation of phosphoinositol-3 kinase (PI3K)-protein kinase B (AKT) signaling pathway. What is more, trans isomer (ISRIB), a targeted inhibitor of NUP85, could alleviate NAFLD. In summary, our findings suggested that NUP85 functions as an important regulator in NAFLD through modulation of CCR2.

Hapln1 promotes dedifferentiation and proliferation of iPSC-derived cardiomyocytes by promoting versican-based GDF11 trapping.

Hyaluronan and proteoglycan link protein 1 (Hapln1) supports active cardiomyogenesis in zebrafish hearts, but its regulation in mammal cardiomyocytes is unclear. This study aimed to explore the potential regulation of Hapln1 in the dedifferentiation and proliferation of cardiomyocytes and its therapeutic value in myocardial infarction with human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CMs) and an adult mouse model of myocardial infarction. HiPSC-CMs and adult mice with myocardial infarction were used as in vitro and in vivo models, respectively. Previous single-cell RNA sequencing data were retrieved for bioinformatic exploration. The results showed that recombinant human Hapln1 (rhHapln1) promotes the proliferation of hiPSC-CMs in a dose-dependent manner. As a physical binding protein of Hapln1, versican interacted with Nodal growth differentiation factor (NODAL) and growth differentiation factor 11 (GDF11). GDF11, but not NODAL, was expressed by hiPSC-CMs. GDF11 expression was unaffected by rhHapln1 treatment. However, this molecule was required for rhHapln1-mediated activation of the transforming growth factor (TGF)-ß/Drosophila mothers against decapentaplegic protein (SMAD)2/3 signaling in hiPSC-CMs, which stimulates cell dedifferentiation and proliferation. Recombinant mouse Hapln1 (rmHapln1) could induce cardiac regeneration in the adult mouse model of myocardial infarction. In addition, rmHapln1 induced hiPSC-CM proliferation. In conclusion, Hapln1 can stimulate the dedifferentiation and proliferation of iPSC-derived cardiomyocytes by promoting versican-based GDF11 trapping and subsequent activation of the TGF-ß/SMAD2/3 signaling pathway. Hapln1 might be an effective hiPSC-CM dedifferentiation and proliferation agent and a potential reagent for repairing damaged hearts.

Projecting heat-related cardiovascular mortality burden attributable to human-induced climate change in China.

BACKGROUND: Cardiovascular disease (CVD) has been found to be particularly vulnerable to climate change and temperature variability. This study aimed to assess the extent to which human-induced climate change contributes to future heat-related CVD burdens. METHODS: Daily data on CVD mortality and temperature were collected in 161 Chinese communities from 2007 to 2013. The association between heat and CVD mortality was established using a two-stage time-series design. Under the natural forcing, human-induced, and combined scenarios, we then separately projected excess cause-/age-/region-/education-specific mortality from future high temperature in 2010-2100, assuming no adaptation and population changes. FINDINGS: Under shared socioeconomic pathway with natural forcing scenario (SSP2-4.5-nat), heat-related attributable fraction of CVD deaths decreased slightly from 3.3% [95% empirical confidence interval (eCI): 0.3, 5.8] in the 2010s to 2.8% (95% eCI: 0.1, 5.2) in the 2090s, with relative change of -0.4% (95% eCI: -0.8, 0.0). However, for combined natural and human-induced forcings, this estimate would surge to 8.9% (95% eCI: 1.5, 15.7), 14.4% (95% eCI: 1.5, 25.3), 21.3% (95% eCI: -0.6, 39.4), and 28.7% (95% eCI: -3.3, 48.0) in the 2090s under SSP1-2.6, SSP2-4.5, SSP3-7.0, and SSP5-8.5 scenarios, respectively. When excluding the natural forcing, the number of human-induced heat-related CVD deaths would increase from approximately eight thousand (accounting for 31% of total heat-related CVD deaths) in the 2010s to 33,052 (68%), 63,283 (80%), 101,091 (87%), and 141,948 (90%) in the 2090s under SSP1-2.6, SSP2-4.5, SSP3-7.0, and SSP5-8.5 scenarios, respectively. Individuals with stroke, females, the elderly, people living in rural areas, and those with lower education level would exhibit heightened susceptibility to future high temperature. In addition, Southern and Eastern regions of China were expected to experience a faster increase in heat-related attributable fraction of CVD deaths. INTERPRETATION: Human activities would significantly amplify the future burden of heat-related CVD. Our study findings suggested that active adaptation and mitigation measures towards future warming could yield substantial health benefits for the patients with CVD. FUNDING: National Natural Science Foundation of China.

Nontargeted Analysis of Coumarins in Source Water and Their Formation of Chlorinated Coumarins as DBPs in Drinking Water.

Coumarin was detected as one of the most abundant compounds by nontargeted analysis of natural product components in actual water samples prior to disinfection. More importantly, prechlorination of humic acid generated 3-hydroxycoumarin and monohydroxy-monomethyl-substituted coumarin with a total yield of ≤10.1%, which suggested the humic substance in raw water is an important source of coumarins. 7-Hydroxycoumarin, 6-hydroxy-4-methylcoumarin, 6,7-dihydroxycoumarin, and 7-methoxy-4-methylcoumarin were identified in raw water by high-performance liquid chromatography-tandem high-resolution mass spectrometry because only some coumarin standards were commercially available. Their chlorination generated monochlorinated and polychlorinated coumarins, and their structures were confirmed by the synthesized standards. These products could form at various dosages of chlorine and pH levels, and some with a concentration of 600 ng/L can be stable in tap water for days. 3,6,8-Trichloro-7-hydroxycoumarin, 3-chloro-7-methoxy-4-methylcoumarin, and 3,6-dichloro-7-methoxy-4-methylcoumarin were first identified in finished water with concentrations of 0.0670, 78.1, and 14.7 ng/L, respectively, but not in source water, suggesting that they are new DBPs formed during disinfection. The cytotoxicity of 3-chloro-7-methoxy-4-methylcoumarin in CHO-K1 cells was comparable to those of 2,6-dibromo-1,4-benzoquinone and 2,6-dichloro-1,4-benzoquinone in TIC-Tox analyses, suggesting that further investigation of their occurrence and control in drinking water systems is warranted.

A safety and efficacy study of allogeneic haematopoietic stem cell transplantation for refractory and relapsed T-cell acute lymphoblastic leukaemia/lymphoblastic lymphoma patients who achieved complete remission after autologous CD7 chimeric antigen receptor T-cell therapy.

CD7-targeted chimeric antigen receptor T-cell (CAR-T) therapy has shown promising initial complete remission (CR) rates in patients with refractory or relapsed (r/r) T-cell acute lymphoblastic leukaemia and lymphoblastic lymphoma (T-ALL/LBL). To enhance the remission duration, consolidation with allogeneic haematopoietic stem cell transplantation (allo-HSCT) is considered. Our study delved into the outcomes of 34 patients with r/r T-ALL/LBL who underwent allo-HSCT after achieving CR with autologous CD7 CAR-T therapy. These were compared with 124 consecutive T-ALL/LBL patients who received allo-HSCT in CR following chemotherapy. The study revealed that both the CAR-T and chemotherapy cohorts exhibited comparable 2-year overall survival (OS) (61.9% [95% CI, 44.1-78.1] vs. 67.6% [95% CI, 57.5-76.9], p = 0.210), leukaemia-free survival (LFS) (62.3% [95% CI, 44.6-78.4] vs. 62.0% [95% CI, 51.8-71.7], p = 0.548), non-relapse mortality (NRM) rates (32.0% [95% CI, 19.0-54.0] vs. 25.3% [95% CI, 17.9-35.8], p = 0.288) and relapse incidence rates (8.8% [95% CI, 3.0-26.0] vs. 15.8% [95% CI, 9.8-25.2], p = 0.557). Patients aged ≤14 in the CD7 CAR-T group achieved high 2-year OS and LFS rates of 87.5%. Our study indicates that CD7 CAR-T therapy followed by allo-HSCT is not only effective and safe for r/r T-ALL/LBL patients but also on par with the outcomes of those achieving CR through chemotherapy, without increasing NRM.

Characteristic Fingerprint Spectrum of α-Synuclein Mutants on Terahertz Time-Domain Spectroscopy.

OBJECTIVE: Alpha-Synuclein (α-Syn), a presynaptic neuronal protein encoded by the SNCA gene, is involved in the pathogenesis of Parkinson's disease. Point mutations and multiplications of the α-Syn (A30P and A53T) are correlated with early-onset Parkinson's disease characterized by rapid progression and poor prognosis. Currently, the clinical identification of SNCA variants, especially disease-related A30P and A53T mutants, remains challenging and also time-consuming. This study has aimed to develop a novel label-free detection method for distinguishing the SNCA mutants using transmission terahertz (THz) time-domain spectroscopy. METHODS: The protein was spin-coated onto the quartz to form a thin film, which was measured using THz time-domain spectroscopy. The spectral characteristics of THz broadband pulse waves of α-Syn protein variants (SNCA wild type [WT], A30P, and A53T) at different frequencies were analyzed via Fourier transform. RESULTS: The amplitude A intensity (AWT, AA30P, and AA53T) and peak occurrence time in THz-TDS sensitively distinguished the three protein variants. The phase φ difference in THz frequency domain followed the trend of φWT>φA30P>φA53T. There was a significant difference in THz frequency amplitude A' corresponding to the frequency ranging from 0.4 THz to 0.66 THz (A'A53T>A'A30P>A'WT). At a frequency of 0.4-0.6 THz, the transmission T of THz waves distinguished three variants (TA53T>TA30P>TWT), while there was no difference in the transmission T at 0.66 THz. CONCLUSION: The SNCA wild-type protein and two mutant variants (A30P and A53T) had distinct characteristic fingerprint spectra on THz time-domain spectroscopy. This novel label-free detection method has great potential for the differential diagnosis of Parkinson's disease subtypes.

Hepatopulmonary syndrome: Case report of the evidence of intrapulmonary shunt on 99mTc-MAA scintigraphy and contrast transthoracic echocardiography.

The hepatopulmonary syndrome (HPS) is characterized by arterial oxygenation defect induced by intrapulmonary vascular dilatations in the setting of liver disease. We report a 57-year-old woman with a history of liver cirrhosis presented with progressive cyanosis, exertional dyspnea and a dry cough. Oxyhemoglobin saturation was 88.5% on room air. Contrast transthoracic echocardiography (cTTE) and technetium-99m-macroaggregated albumin (99mTc-MAA) scintigraphy showed an intrapulmonary shunting and confirmed HPS.

PLD2 deletion ameliorates sepsis-induced cardiomyopathy by suppressing cardiomyocyte pyroptosis via the NLRP3/caspase 1/GSDMD pathway.

OBJECTIVE: Sepsis-induced cardiomyopathy (SICM) is a life-threatening complication. Phospholipase D2 (PLD2) is crucial in mediating inflammatory reactions and is associated with the prognosis of patients with sepsis. Whether PLD2 is involved in the pathophysiology of SICM remains unknown. This study aimed to investigate the effect of PLD2 knockout on SICM and to explore potential mechanisms. METHODS: The SICM model was established using cecal ligation and puncture in wild-type and PLD2-knockout mice and lipopolysaccharide (LPS)-induced H9C2 cardiomyocytes. Transfection with PLD2-shRNA lentivirus and a PLD2 overexpression plasmid were used to interfere with PLD2 expression in H9C2 cells. Cardiac pathological alterations, cardiac function, markers of myocardial injury, and inflammatory factors were used to evaluate the SICM model. The expression of pyroptosis-related proteins (NLRP3, cleaved caspase 1, and GSDMD-N) was assessed using western blotting, immunofluorescence, and immunohistochemistry. RESULTS: SICM mice had myocardial tissue damage, increased inflammatory response, and impaired heart function, accompanied by elevated PLD2 expression. PLD2 deletion improved cardiac histological changes, mitigated cTNI production, and enhanced the survival of the SICM mice. Compared with controls, PLD2-knockdown H9C2 exhibits a decrease in inflammatory markers and lactate dehydrogenase production, and scanning electron microscopy results suggest that pyroptosis may be involved. The overexpression of PLD2 increased the expression of NLRP3 in cardiomyocytes. In addition, PLD2 deletion decreased the expression of pyroptosis-related proteins in SICM mice and LPS-induced H9C2 cells. CONCLUSION: PLD2 deletion is involved in SICM pathogenesis and is associated with the inhibition of the myocardial inflammatory response and pyroptosis through the NLRP3/caspase 1/GSDMD pathway.

Correlation analysis between left ventricular global longitudinal strain and major adverse cardiovascular event occurrence in patients with end-stage renal disease.

OBJECTIVE: To explore the correlation between left ventricular global longitudinal strain (LVGLS) and major adverse cardiovascular event (MACE) occurrence in patients with end-stage renal disease (ESRD). METHODS: From January 2019 to December 2023, ESRD patients undergoing maintenance dialysis and LVGLS measurement admitted to the First People's Hospital of Lanzhou City were selected as subjects. They were followed up for 12 months to record the occurrence of MACEs, and divided into MACE group and non-MACE group according to MACE presence or absence. RESULTS: A total of 158 ESRD patients were included, with 32 patients in the MACE group and 126 patients in the non-MACE group. In the MACE group, high-sensitivity C-reactive protein (hs-CRP) level, peak troponin T (TNT) and the ratio of early diastolic mitral inflow velocity to early diastolic septal mitral annulus velocity (E/e') were higher, while hemoglobin, left ventricular ejection fraction (LVEF) and absolute LVGLS were lower compared with the non-MACE group (P < 0.05). Multivariate COX regression analysis revealed that LVGLS (HR = 1.06, 95% CI 1.02-1.10) and hs-CRP (HR = 1.17, 95% CI 1.23-1.31) were independent predictors of MACE occurrence in ESRD patients (P < 0.05). The area under the ROC curve (AUC) for MACE occurrence within 12 months was 0.83 (95% CI 0.74-0.95), with a sensitivity of 89.9% and a specificity of 76.8%. The MACE-free survival rate in the high LVGLS group was higher compared to the low LVGLS group (P < 0.05). CONCLUSION: Reduced LVGLS is an independent risk factor for MACE occurrence in ESRD patients within 12 months and a good prognostic indicator.

Risk stratification and predictive modeling of postoperative delirium in chronic subdural hematoma.

Background- Postoperative delirium is a common complication associated with the elderly, causing increased morbidity and prolonged hospital stay. However, its risk factors in chronic subdural hematoma patients have not been well studied. Methods- A total of 202 consecutive patients with chronic subdural hematoma at Peking University Third Hospital between January 2018 and January 2023 were enrolled. Various clinical indicators were analyzed to identify independent risk factors for postoperative delirium using univariate and multivariate regression analyses. Delirium risk prediction models were developed as a nomogram and a Markov chain. Results- Out of the 202 patients (age, 71 (IQR, 18); female-to-male ratio, 1:2.7) studied, 63 (31.2%) experienced postoperative delirium. Univariate analysis identified age (p < 0.001), gender (p = 0.014), restraint belt use (p < 0.001), electrolyte imbalance (p < 0.001), visual analog scale score (p < 0.001), hematoma thickness (p < 0.001), midline shift (p < 0.001), hematoma side (p = 0.013), hematoma location (p = 0.018), and urinal catheterization (p = 0.028) as significant factors. Multivariate regression analysis confirmed the significance of restraint belt use (B = 7.657, p < 0.001), electrolyte imbalance (B = -3.993, p = 0.001), visual analog scale score (B = 2.331, p = 0.016), and midline shift (B = 0.335, p = 0.007). Hematoma thickness and age had no significant impact. Conclusion- Increased midline shift and visual analog scale scores, alongside restraint belt use and electrolyte imbalance elevate delirium risk in chronic subdural hematoma surgery. Our prediction models may offer reference value in this context.

Discharge coefficient of vertical sluice gates with broad crested weir under free-submerged orifice flows using best subset regression.

Accurate calculation of flow discharge for sluice gates is essential in irrigation, water supply, and structure safety. The measurement of discharge with the requirement of distinguishing flow regimes is not conducive to application. In this study, a novel approach that considers both free and submerged flow was proposed. The energy-momentum method was employed to derive the coefficient of discharge. Subsequently, the discharge coefficient was determined through the experiment which was performed on the physical model of a vertical sluice gate with a broad-crested weir. Feature engineering, incorporating dimensional analysis, feature construction, and correlation-based selection were performed. The best subset regression method was employed to develop regression equations of the discharge coefficient with the generated features. The derived formula was applied to compute the discharge coefficient in the vertical sluice gate and determine the flow discharge. The accuracy of adopted method was assessed by comparing it with recent studies on submerged flow, and the results demonstrate that the developed approach achieves a high level of accuracy in calculating flow discharge. The coefficient of determination for the calculated flow rate is 0.993, and the root mean square percentage error is 5.04%.

A mix & act liposomes of phospholipase A2-phosphatidylserine for acute brain detoxification by blood‒brain barrier selective-opening.

In the treatment of central nervous system disease, the blood-brain barrier (BBB) is a major obstruction to drug delivery that must be overcome. In this study, we propose a brain-targeted delivery strategy based on selective opening of the BBB. This strategy allows some simple bare nanoparticles to enter the brain when mixed with special opening material; however, the BBB still maintains the ability to completely block molecules from passing through. Based on the screening of BBB opening and matrix delivery materials, we determined that phospholipase A2-catalyzed 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoserine liposomes can efficiently carry drugs into the brain immediately. At an effective dose, this delivery system is safe, especially with its effect on the BBB being reversible. This mix & act delivery system has a simple structure and rapid preparation, making it a strong potential candidate for drug delivery across the BBB.

A Modified Algorithm-Based Levator Aponeurectomy in Mild to Moderate Congenital Blepharoptosis.

BACKGROUND: Levator aponeurectomy is a common operation for mild to moderate blepharoptosis. The accuracy of ptosis correction relied on intraoperative judgement when patients were under local anesthesia. For patients who must receive the operation under general anesthesia, it would be an issue to determine how much length of levator aponeurosis to shorten. To solve this issue, we collected data from patients who underwent the operation under local anesthesia and concluded an algorithm. METHODS: This single-center, prospective bivariate regression study allocated patients of mild to moderate congenital blepharoptosis who received levator aponeurectomy under local anesthesia. Preoperative MRD1 and levator function, intraoperative amount of levator aponeurotic shortening, and postoperative MRD1 were measured. The follow-up period was right after the operation. RESULTS: Twenty-nine patients were included in this trial. Two subjects exited because of not receiving allocated operation and data of the other 27 subjects (including 34 eyelids) were analyzed. A scatter diagram was drawn where x axis referred to levator function and y axis referred to the ratio of the amount of shortening of levator aponeurosis over the height of MRD1 correction. Linear regression showed y = - 0.2717*x + 5.026, R2 = 0.8553. CONCLUSION: A modified algorithm to predict the amount of shortening of levator aponeurosis based on levator function and height of ptosis correction was concluded with better accuracy and clinical feasibility. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Conditional c-MYC activation in catecholaminergic cells drives distinct neuroendocrine tumors: neuroblastoma vs somatostatinoma.

The MYC proto-oncogenes (c-MYC, MYCN , MYCL ) are among the most deregulated oncogenic drivers in human malignancies including high-risk neuroblastoma, 50% of which are MYCN -amplified. Genetically engineered mouse models (GEMMs) based on the MYCN transgene have greatly expanded the understanding of neuroblastoma biology and are powerful tools for testing new therapies. However, a lack of c-MYC-driven GEMMs has hampered the ability to better understand mechanisms of neuroblastoma oncogenesis and therapy development given that c-MYC is also an important driver of many high-risk neuroblastomas. In this study, we report two transgenic murine neuroendocrine models driven by conditional c-MYC induction in tyrosine hydroxylase (Th) and dopamine ß-hydroxylase (Dbh)-expressing cells. c-MYC induction in Th-expressing cells leads to a preponderance of Pdx1 + somatostatinomas, a type of pancreatic neuroendocrine tumor (PNET), resembling human somatostatinoma with highly expressed gene signatures of δ cells and potassium channels. In contrast, c-MYC induction in Dbh-expressing cells leads to onset of neuroblastomas, showing a better transforming capacity than MYCN in a comparable C57BL/6 genetic background. The c-MYC murine neuroblastoma tumors recapitulate the pathologic and genetic features of human neuroblastoma, express GD2, and respond to anti-GD2 immunotherapy. This model also responds to DFMO, an FDA-approved inhibitor targeting ODC1, which is a known MYC transcriptional target. Thus, establishing c-MYC-overexpressing GEMMs resulted in different but related tumor types depending on the targeted cell and provide useful tools for testing immunotherapies and targeted therapies for these diseases.

A novel frameshift mutation in RHAG leads to Rhnull phenotype in a Chinese individual.

BACKGROUND: We recently encountered a Rhnull phenotype proband within one family in the Chinese population. Rhnull is a rare autosomal recessive disorder characterized by the absence of the Rh antigens on the erythrocyte membrane, resulting in chronic hemolytic anemia. This study described the serological and molecular analysis of a Chinese Rhnull proband and his immediate family. METHODS: Red blood cells antigen phenotyping and antibody screening/identification were conducted. RHD, RHCE, and RHAG were analyzed using genomic DNA by polymerase chain reaction and sequence analysis. RESULTS: Serologic tests showed a D-C-E-c-e- phenotype in the proband associated with the suspicion of anti-Rh29 (titer 16). Molecular analyses showed a new mutation (c.406dupA) in exon 3 of RHAG. This duplication introduced a reading frameshift (p.Thr136AsnfsTer21). The RHAG mutation was found in the homozygous state for the proband and heterozygous state for his parents. CONCLUSION: We identified a novel RHAG mutation resulting in the Rhnull phenotype of the regulator type. Inheritance of the novel allele was shown by family study.

Packaged structure optimization for enhanced light extraction efficiency and reduced thermal resistance of ultraviolet B LEDs.

Ultraviolet B light-emitting diodes (UVB LEDs) hold promise in medical and agricultural applications. The commonly used sapphire substrate for their epitaxy growth possesses a high refractive index and excellent UV light absorption characteristics. However, this high refractive index can induce total internal reflection (TIR) within the substrate, leading to decreased Light Extraction Efficiency (LEE) due to light absorption within the material. In this study, UVB LED chips were detached from the sub-mount substrate and directly affixed onto an aluminum nitride (AlN) substrate with superior heat dissipation using a eutectic process. This was undertaken to diminish packaged thermal resistance (PTR). Simultaneously, optimization of the UVB LED packaging structure was employed to alleviate LEE losses caused by the TIR phenomenon, with the overarching goal of enhancin external quantum efficiency (EQE). The final experimental findings suggest that optimal LEE is achieved with packaging dimensions, including a length (ELL) of 2 mm, a width (ELW) of 1.62 mm, and a height (ELH) of 0.52 mm. At an input current of 200 mA, the output power reaches 50 mW, resulting in an EQE of 6.3%. Furthermore, the packaged thermal resistance from the chip to the substrate surface can be reduced to 4.615 K/W.

Full-angle chip scale package of mini LEDs with a V-shape packaging structure.

The light distribution of light-emitting diodes (LEDs) generally resembles that of a Lambertian light source. When used as large-area light sources, the light distribution angle of LEDs must be modified through secondary optics design to achieve uniformity and minimize the number of light sources. However, secondary optical components pose several challenges such as demanding alignment accuracy, material aging, detachment, and lower reliability. Therefore, this paper proposes a primary optical design approach to achieve full-angle emission in LEDs without the need for lenses. The design employs a flip-chip as the light source and incorporates a V-shaped packaged structure, including a white wall layer, optical structure layers, and a V-shaped diffuse structure. With this design, the LEDs achieve full-angle emission without relying on lenses. Our experimental results demonstrated a peak intensity angle of 77.7°, a 20.3% decrease in the intensity of the central point ratio, and a full width at half maximum (FWHM) of the light distribution of 175.5°. This design is particularly suitable for thin, large-area, and flexible backlight light sources. Moreover, the absence of secondary optical components allows for a thinner light source module.

CD9 shapes glucocorticoid sensitivity in pediatric B-cell precursor acute lymphoblastic leukemia.

Resistance to glucocorticoids (GCs), the common agents for remission induction in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL), poses a significant therapeutic hurdle. Therefore, dissecting the mechanisms shaping GC resistance could lead to new treatment modalities. Here, we showed that CD9- BCP-ALL cells were preferentially resistant to prednisone and dexamethasone over other standard cytotoxic agents. Concordantly, we identified significantly more poor responders to the prednisone prephase among BCP-ALL patients with a CD9- phenotype, especially for those with adverse presenting features including older age, higher white cell count and BCR-ABL1. Furthermore, gain- and loss-of-function experiments dictated a definitive functional linkage between CD9 expression and GC susceptibility, as demonstrated by the reversal and acquisition of relative GC resistance in CD9low and CD9high BCP-ALL cells, respectively. Despite physical binding to the GC receptor NR3C1, CD9 did not alter its expression, phosphorylation or nuclear translocation but potentiated the induction of GC-responsive genes in GCresistant cells. Importantly, the MEK inhibitor trametinib exhibited higher synergy with GCs against CD9- than CD9+ lymphoblasts to reverse drug resistance in vitro and in vivo. Collectively, our results elucidate a previously unrecognized regulatory function of CD9 in GC sensitivity, and inform new strategies for management of children with resistant BCP-ALL.