The demise of the giant ape Gigantopithecus blacki.

The largest ever primate and one of the largest of the southeast Asian megafauna, Gigantopithecus blacki1, persisted in China from about 2.0 million years until the late middle Pleistocene when it became extinct2-4. Its demise is enigmatic considering that it was one of the few Asian great apes to go extinct in the last 2.6 million years, whereas others, including orangutan, survived until the present5. The cause of the disappearance of G. blacki remains unresolved but could shed light on primate resilience and the fate of megafauna in this region6. Here we applied three multidisciplinary analyses-timing, past environments and behaviour-to 22 caves in southern China. We used 157 radiometric ages from six dating techniques to establish a timeline for the demise of G. blacki. We show that from 2.3 million years ago the environment was a mosaic of forests and grasses, providing ideal conditions for thriving G. blacki populations. However, just before and during the extinction window between 295,000 and 215,000 years ago there was enhanced environmental variability from increased seasonality, which caused changes in plant communities and an increase in open forest environments. Although its close relative Pongo weidenreichi managed to adapt its dietary preferences and behaviour to this variability, G. blacki showed signs of chronic stress and dwindling populations. Ultimately its struggle to adapt led to the extinction of the greatest primate to ever inhabit the Earth.

Atomically Resolved Transition Pathways of Iron Redox.

The redox transition between iron and its oxides is of the utmost importance in heterogeneous catalysis, biological metabolism, and geological evolution. The structural characteristics of this reaction may vary based on surrounding environmental conditions, giving rise to diverse physical scenarios. In this study, we explore the atomic-scale transformation of nanosized Fe3O4 under ambient-pressure H2 gas using in-situ environmental transmission electron microscopy. Our results reveal that the internal solid-state reactions dominated by iron diffusion are coupled with the surface reactions involving gaseous O or H species. During reduction, we observe two competitive reduction pathways, namely Fe3O4 → FeO → Fe and Fe3O4 → Fe. An intermediate phase with vacancy ordering is observed during the disproportionation reaction of Fe2+ → Fe0 + Fe3+, which potentially alleviates stress and facilitates ion migration. As the temperature decreases, an oxidation process occurs in the presence of environmental H2O and trace amounts of O2. A direct oxidation of Fe to Fe3O4 occurs in the absence of the FeO phase, likely corresponding to a change in the water vapor content in the atmosphere. This work elucidates a full dynamical scenario of iron redox under realistic conditions, which is critical for unraveling the intricate mechanisms governing the solid-solid and solid-gas reactions.

Seasonal variation of two floral patterns in Clematis 'Vyvyan Pennell' and its underlying mechanism.

BACKGROUND: Floral patterns are crucial for insect pollination and plant reproduction. Generally, once these patterns are established, they exhibit minimal changes under natural circumstances. However, the Clematis cultivar' Vyvyan Pennell', the apetalous lineage in the Ranunculaceae family, produces two distinct types of flowers during different seasons. The regulatory mechanism responsible for this phenomenon remains largely unknown. In this study, we aim to shed light on this floral development with shifting seasonal patterns by conducting extensive morphological, transcriptomic, and hormone metabolic analyses. Our findings are anticipated to contribute valuable insights into the diversity of flowers in the Ranunculaceae family. RESULTS: The morphological analysis revealed that the presence of extra petaloid structures in the spring double perianth was a result of the transformation of stamens covered with trichomes during the 5th developmental stage. A de novo reference transcriptome was constructed by comparing buds and organs within double and single perianth from both seasons. A total of 209,056 unigenes were assembled, and 5826 genes were successfully annotated in all six databases. Among the 69,888 differentially expressed genes from the comparative analysis, 48 genes of utmost significance were identified. These critical genes are associated with various aspects of floral development. Interestingly, the A-, B-, and C-class genes exhibited a wider range of expression and were distinct within two seasons. The determination of floral organ identity was attributed to the collaborative functioning of all the three classes genes, aligning with a modified "fading border model". The phytohormones GA3, salicylic acid, and trans-zeatin riboside may affect the formation of the spring double perianth, whereas GA7 and abscisic acid may affect single flowers in autumn. CONCLUSIONS: We presumed that the varying temperatures between the two seasons served as the primary factor in the alteration of floral patterns, potentially affecting the levels of plant hormones and expressions of organ identity genes. However, a more thorough investigation is necessary to fully comprehend the entire regulatory network. Nonetheless, our study provides some valuable informations for understanding the underlying mechanism of floral pattern alterations in Clematis.

Generalizable transcriptome-based tumor malignant level evaluation and molecular subtyping towards precision oncology.

In cancer treatment, therapeutic strategies that integrate tumor-specific characteristics (i.e., precision oncology) are widely implemented to provide clinical benefits for cancer patients. Here, through in-depth integration of tumor transcriptome and patients' prognoses across cancers, we investigated dysregulated and prognosis-associated genes and catalogued such important genes in a cancer type-dependent manner. Utilizing the expression matrices of these genes, we built models to quantitatively evaluate the malignant levels of tumors across cancers, which could add value to the clinical staging system for improved prediction of patients' survival. Furthermore, we performed a transcriptome-based molecular subtyping on hepatocellular carcinoma, which revealed three subtypes with significantly diversified clinical outcomes, mutation landscapes, immune microenvironment, and dysregulated pathways. As tumor transcriptome was commonly profiled in clinical practice with low experimental complexity and cost, this work proposed easy-to-perform approaches for practical clinical promotion towards better healthcare and precision oncology of cancer patients.

Viral communities in a pH>10 serpentinite-like environment: insight into diversity and potential roles in modulating the microbiomes by bioactive vitamin B9 synthesis.

Viral communities exist in a variety of ecosystems and play significant roles in mediating biogeochemical processes, whereas viruses inhabiting strongly alkaline geochemical systems remain underexplored. In this study, the viral diversity, potential functionalities, and virus-host interactions in a strongly alkaline environment (pH = 10.4-12.4) exposed to the leachates derived from the serpentinization-like reactions of smelting slags were investigated. The viral populations (e.g., Herelleviridae, Queuovirinae, and Inoviridae) were closely associated with the dominating prokaryotic hosts (e.g., Meiothermus, Trueperaceae, and Serpentinomonas) in this ultrabasic environment. Auxiliary metabolic genes (AMGs) suggested that viruses may enhance hosts' fitness by facilitating cofactor biosynthesis, hydrogen metabolism, and carbon cycling. To evaluate the activity of synthesis of essential cofactor vitamin B9 by the viruses, a viral folA (vfolA) gene encoding dihydrofolate reductase (DHFR) was introduced into a thymidine-auxotrophic strain Escherichia coli MG1655 ΔfolA mutant, which restored the growth of the latter in the absence of thymidine. Notably, the homologs of the validated vDHFR were globally distributed in the viromes across various ecosystems. The present study sheds new light on the unique viral communities in hyperalkaline ecosystems and their potential beneficial impacts on the coexisting microbial consortia by supplying essential cofactors. IMPORTANCE: This study presents a comprehensive investigation into the diversity, potential functionalities, and virus-microbe interactions in an artificially induced strongly alkaline environment. Functional validation of the detected viral folA genes encoding dihydrofolate reductase substantiated the synthesis of essential cofactors by viruses, which may be ubiquitous, considering the broad distribution of the viral genes associated with folate cycling.

Quaternary pulse width modulation based ultra-high frame rate scene projector used for hard-ware-in-the-loop testing.

The scene projector (SP) can provide simulated scene images with same optical characteristics as the real scenes to evaluate imaging systems in hard-ware-in-the-loop (HWIL) simulation testing. The single scene generation device (SGD) based SP typically projects 8-bit images at 220 fps, which is insufficient to fulfill the requirements of ultra-high frame rate imaging systems, such as star trackers and space debris detectors. In this paper, an innovative quaternary pulse width modulation (PWM) based SP is developed and implemented to realize the ultra-high frame rate projection. By optically overlapping modulation layers of two digital micro-mirror devices (DMDs) in parallel, and illuminating them with light intensities, a quaternary SGD is built up to modulate quaternary digit-planes (QDs) with four grayscale levels. And the quaternary digit-plane de-composition (QDD) is adopted to decompose an 8-bit image into 4 QDs. In addition, the exposure time of each QD is controlled by quaternary PWM, and the base time is optimized to 8 µs. The experimental results prove that the total exposure time of all QDs sequentially modulated by quaternary PWM is approximately 760 µs, namely projecting 8-bit images at 1300 fps. The quaternary PWM using two DMDs in parallel dramatically improves the grayscale modulation efficiency compared to the existing projection technologies, which provides a new approach for the SP design with ultra-high frame rate.

Echelon grating refractive index sensor.

There are few reports on optical refractive index sensors that have both high resonant-wavelength resolution (RWR) and high refractive index sensitivity (RIS). Herein, based on an echelon grating, we design a refractive index sensor that combines the two advantages together. The principal fringe of echelon grating has a small full width at half maximum and a good signal-to-noise ratio, leading to a high RWR. The wavefront splitting interference makes the sensor have high RIS. The large free spectral range (FSR) of the principal fringes expands the dynamic range of the sensor. The experimentally realized RWR, RIS, and FSR are 2 × 10-2 nm, 1.14 × 104 nm/RIU (RIU: refractive index unit), and 130 nm, respectively. The detection limit of refractive index is 1.59 × 10-6 RIU. The dynamic range of the sensor is 1.14 × 10-2 RIU. In addition, there are schemes to improve RWR and RIS, which can further reduce the detection limit of refractive index. The echelon grating refractive index sensor features low detection limit, low cost, high stability, and good robustness.

TetR family regulator AbrT controls lincomycin production and morphological development in Streptomyces lincolnensis.

BACKGROUND: The TetR family of transcriptional regulators (TFRs), serving as crucial regulators of diverse cellular processes, undergo conformational changes induced by small-molecule ligands, which either inhibit or activate them to modulate target gene expression. Some ligands of TFRs in actinomycetes and their regulatory effects have been identified and studied; however, regulatory mechanisms of the TetR family in the lincomycin-producing Streptomyces lincolnensis remain poorly understood. RESULTS: In this study, we found that AbrT (SLCG_1979), a TetR family regulator, plays a pivotal role in regulating lincomycin production and morphological development in S. lincolnensis. Deletion of abrT gene resulted in increased lincomycin A (Lin-A) production, but delayed mycelium formation and sporulation on solid media. AbrT directly or indirectly repressed the expression of lincomycin biosynthetic (lin) cluster genes and activated that of the morphological developmental genes amfC, whiB, and ftsZ. We demonstrated that AbrT bound to two motifs (5'-CGCGTACTCGTA-3' and 5'-CGTACGATAGCT-3') present in the bidirectional promoter between abrT and SLCG_1980 genes. This consequently repressed abrT itself and its adjacent gene SLCG_1980 that encodes an arabinose efflux permease. D-arabinose, not naturally occurring as L-arabinose, was identified as the effector molecule of AbrT, reducing its binding affinity to abrT-SLCG_1980 intergenic region. Furthermore, based on functional analysis of the AbrT homologue in Saccharopolyspora erythraea, we inferred that the TetR family regulator AbrT may play an important role in regulating secondary metabolism in actinomycetes. CONCLUSIONS: AbrT functions as a regulator for governing lincomycin production and morphological development of S. lincolnensis. Our findings demonstrated that D-arabinose acts as a ligand of AbrT to mediate the regulation of lincomycin biosynthesis in S. lincolnensis. Our findings provide novel insights into ligand-mediated regulation in antibiotic biosynthesis.

Profiling of urinary steroids aided by lithium ion adduction-based ultrahigh-performance liquid chromatography-tandem mass spectrometry.

RATIONALE: As 3-OH-containing steroids are prone to dehydration by conventional electrospray ionization, reducing detection sensitivity, Li ion adduction-based ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC/MS/MS), developed to prevent dehydration and effectively detect 3-OH steroids, was applied for profiling total and free steroids in urine. METHODS: Free urinary steroids were isolated directly from urine by solid-phase extraction (SPE) with 80% acetonitrile. The total steroids were prepared by enzymatic treatment of urine with a cocktail of sulfatase and glucronidase, protein precipitation, and separation with the above SPE. In order to detect as many steroid types as possible, UHPLC/MS/MS (Li method) with Li+ solution added after the column was used for analysis in addition to the conventional method of detecting protonated ions (H method). The 13 3-OH steroids and the remaining 16 steroids were quantified by standard curves prepared using product ion transitions derived from [M + Li]+ and MH+ , respectively. RESULTS: Two groups of human urine, male and female urine, were analyzed. 3-OH steroids could be detected with greater sensitivity using the Li method than the conventional method. The absolute amounts of each steroid were normalized based on creatinine levels. The difference between the male and female groups are clearly attributable to sex steroids. CONCLUSIONS: Twenty-nine total steroids and 19 free steroids were identified in a limited volume (240 mL) of urine. Of these, 13 3-OH steroids were better detected by Li+ adduction-based UHPLC/MS/MS.

Discovery of an ellipticine derivative as TLR3 inhibitor against influenza A virus and SARS-CoV-2.

Influenza and COVID-19 continue to pose global threats to public health. Classic antiviral drugs have certain limitations, coupled with frequent viral mutations leading to many drugs being ineffective, the development of new antiviral drugs is urgent. Meanwhile, the invasion of influenza virus can cause an immune response, and an excessive immune response can generate a large number of inflammatory storms, leading to tissue damage. Toll-like receptor 3 (TLR3) recognizes virus dsRNA to ignite the innate immune response, and inhibit TLR3 can block the excess immune response and protect the host tissues. Taking TLR3 as the target, SMU-CX1 was obtained as the specific TLR3 inhibitor by high-throughput screening of 15,700 compounds with IC50 value of 0.11 µM. Its anti-influenza A virus activity with IC50 ranged from 0.14 to 0.33 µM against multiple subtypes of influenza A virus and also showed promising anti-SARS-CoV-2 activity with IC50 at 0.43 µM. Primary antiviral mechanism study indicated that SMU-CX1 significantly inhibited PB2 and NP protein of viruses, it can also inhibit inflammatory factors in host cells including IFN-ß, IP-10 and CCL-5. In conclusion, this study demonstrates the potential of SMU-CX1 in inhibiting IAV and SARS-CoV-2 activity, thereby offering a novel approach for designing antiviral drugs against highly pathogenic viruses.

A novel mutation in hERG gene associated with azithromycin-induced acquired long QT syndrome.

BACKGROUND: Mutations in human ether-à-go-go-related gene (hERG) potassium channels are closely associated with long QT syndrome (LQTS). Previous studies have demonstrated that macrolide antibiotics increase the risk of cardiovascular diseases. To date, the mechanisms underlying acquired LQTS remain elusive. METHODS: A novel hERG mutation I1025N was identified in an azithromycin-treated patient with acquired long QT syndrome via Sanger sequencing. The mutant I1025N plasmid was transfected into HEK-293 cells, which were subsequently incubated with azithromycin. The effect of azithromycin and mutant I1025N on the hERG channel was evaluated via western blot, immunofluorescence, and electrophysiology techniques. RESULTS: The protein expression of the mature hERG protein was down-regulated, whereas that of the immature hERG protein was up-regulated in mutant I1025N HEK-293 cells. Azithromycin administration resulted in a negative effect on the maturation of the hERG protein. Additionally, the I1025N mutation exerted an inhibitory effect on hERG channel current. Moreover, azithromycin inhibited hERG channel current in a concentration-dependent manner. The I1025N mutation and azithromycin synergistically decreased hERG channel expression and hERG current. However, the I1025N mutation and azithromycin did not alter channel gating dynamics. CONCLUSIONS: These findings suggest that hERG gene mutations might be involved in the genetic susceptibility mechanism underlying acquired LQTS induced by azithromycin.

Biosynthesis of eriodictyol in citrus waster by endowing P450BM3 activity of naringenin hydroxylation.

The flavonoid naringenin is abundantly present in pomelo peels, and the unprocessed naringenin in wastes is not friendly for the environment once discarded directly. Fortunately, the hydroxylated product of eriodictyol from naringenin exhibits remarkable antioxidant and anticancer properties. The P450s was suggested promising for the bioconversion of the flavonoids, but less naturally existed P450s show hydroxylation activity to C3' of the naringenin. By well analyzing the catalytic mechanism and the conformations of the naringenin in P450, we proposed that the intermediate Cmpd I ((porphyrin)Fe = O) is more reasonable as key conformation for the hydrolyzation, and the distance between C3'/C5' of naringenin to the O atom of CmpdI determines the hydroxylating activity for the naringenin. Thus, the "flying kite model" that gradually drags the C-H bond of the substrate to the O atom of CmpdI was put forward for rational design. With ab initio design, we successfully endowed the self-sufficient P450-BM3 hydroxylic activity to naringenin and obtained mutant M5-5, with kcat, Km, and kcat/Km values of 230.45 min-1, 310.48 µM, and 0.742 min-1 µM-1, respectively. Furthermore, the mutant M4186 was screened with kcat/Km of 4.28-fold highly improved than the reported M13. The M4186 also exhibited 62.57% yield of eriodictyol, more suitable for the industrial application. This study provided a theoretical guide for the rational design of P450s to the nonnative compounds. KEY POINTS: •The compound I is proposed as the starting point for the rational design of the P450BM3 •"Flying kite model" is proposed based on the distance between O of Cmpd I and C3'/C5' of naringenin •Mutant M15-5 with 1.6-fold of activity than M13 was obtained by ab initio modification.

Nuclear alpha-synuclein accelerates cell senescence and neurodegeneration.

BACKGROUND: The progression of Parkinson's disease (PD) is related to ageing. The accumulation of nuclear alpha-synuclein (α-syn) may accelerate the occurrence of neurodegenerative diseases, but its role in PD remains poorly understood. METHODS: In the present study, α-syn expression was specifically targeted to the nucleus by constructing an adeno-associated virus (AAV) vector in which a nuclear localization sequence (NLS) was added to the α-syn coding sequence. Virus-mediated gene transfer, behavioural tests, RNA-Seq, immunohistochemistry, western blotting, and quantitative real-time PCR were then performed. RESULTS: In vivo experiments using a mouse model showed that nuclear α-syn increased the severity of the PD-like phenotype, including the loss of dopaminergic neurons concomitant with motor impairment and the formation of α-syn inclusions. These nuclear inclusions contained α-syn species of high molecular weights and induced strong transcriptional dysregulation, especially induced high expression of p21 and senescence-associated secretory phenotype (SASP)-related genes. In addition, the transcriptional alterations induced by nuclear α-syn were associated with gliosis, inflammation, oxidative and DNA damage, and lysosomal dysfunction, and they eventually accelerated neuronal loss and neurodegeneration. CONCLUSIONS: Our results suggest that nuclear α-syn plays a crucial role in PD pathogenesis.

Using unsupervised machine learning to classify behavioral risk markers of bacterial vaginosis.

INTRODUCTION: This study used an unsupervised machine learning algorithm, sidClustering and random forests, to identify clusters of risk behaviors of Bacterial Vaginosis (BV), the most common cause of abnormal vaginal discharge linked to STI and HIV acquisition.  METHODS: Participants were 391 cisgender women in Miami, Florida, with a mean of 30.8 (SD = 7.81) years of age; 41.7% identified as Hispanic; 41.7% as Black and 44.8% as White. Participants completed measures of demographics, risk behaviors [sexual, medical, and reproductive history, substance use, and intravaginal practices (IVP)], and underwent collection of vaginal samples; 135 behavioral variables were analyzed. BV was diagnosed using Nugent criteria. RESULTS: We identified four clusters, and variables were ranked by importance in distinguishing clusters: Cluster 1: nulliparous women who engaged in IVPs to clean themselves and please sexual partners, and used substances frequently [n = 118 (30.2%)]; Cluster 2: primiparous women who engaged in IVPs using vaginal douches to clean themselves (n = 112 (28.6%)]; Cluster 3: primiparous women who did not use IVPs or substances [n = 87 (22.3%)]; and Cluster 4: nulliparous women who did not use IVPs but used substances [n = 74 (18.9%)]. Clusters were related to BV (p < 0.001). Cluster 2, the cluster of women who used vaginal douches as IVPs, had the highest prevalence of BV (52.7%). CONCLUSIONS: Machine learning methods may be particularly useful in identifying specific clusters of high-risk behaviors, in developing interventions intended to reduce BV and IVP, and ultimately in reducing the risk of HIV infection among women.

Printed Thick Film Resistance Temperature Detector for Real-Time Tube Furnace Temperature Monitoring.

Accurately acquiring crucial data on tube furnaces and real-time temperature monitoring of different temperature zones is vital for material synthesis technology in production. However, it is difficult to achieve real-time monitoring of the temperature field of tube furnaces with existing technology. Here, we proposed a method to fabricate silver (Ag) resistance temperature detectors (RTDs) based on a blade-coating process directly on the surface of a quartz ring, which enables precise positioning and real-time temperature monitoring of tube furnaces within 100-600 °C range. The Ag RTDs exhibited outstanding electrical properties, featuring a temperature coefficient of resistance (TCR) of 2854 ppm/°C, an accuracy of 1.8% FS (full scale), and a resistance drift rate of 0.05%/h over 6 h at 600 °C. These features ensured accurate and stable temperature measurement at high temperatures. For demonstration purposes, an array comprising four Ag RTDs was installed in a tube furnace. The measured average temperature gradient in the central region of the tube furnace was 5.7 °C/mm. Furthermore, successful real-time monitoring of temperature during the alloy sintering process revealed approximately a 20-fold difference in resistivity for silver-palladium alloys sintered at various positions within the tubular furnace. The proposed strategy offers a promising approach for real-time temperature monitoring of tube furnaces.

Influence of pasteurization and spray drying on the fat digestion behavior of human milk fat analog emulsion: a simulated in vitro infant digestion study.

BACKGROUND: Human milk fat analog emulsion (HMFAE) is an emulsion that mimics the composition and structure of human milk (HM) fat globules. The application of HMFAE in infant formula requires a series of milk powder processing steps, such as pasteurization and spray drying. However, the effect of milk powder processing on fat digestion of HMFAE is still unclear. In this study, the influence of pasteurization and spray drying on the lipolysis behavior of HMFAE was studied and compared with HM using a simulated infant in vitro digestion model. RESULTS: Pasteurization and spray drying increased the flocculation and aggregation of lipid droplets in HMFAE during digestion. Spray drying destroyed the lipid droplet structure of HMFAE, and partial milk fat globule membrane-covered lipid droplets turned into protein-covered lipid droplets, which aggravated lipid-protein aggregation during gastric digestion and hindered fat digestion in the small intestine. The final lipolysis degree was in the order HM (64.55%) > HMFAE (63.41%) > pasteurized HMFAE (61.75%) > spray-dried HMFAE (60.57%). After complete gastrointestinal digestion, there were no significant differences in free fatty acid and sn-2 monoacylglycerol profile among the HMFAE, pasteurized HMFAE, and spray-dried HMFAE. CONCLUSION: Milk powder processing can reduce lipolysis by altering the lipid droplet structure of HMFAE and the degree of lipid droplet aggregation during digestion. © 2024 Society of Chemical Industry.

Role of Cancer Side Population Stem Cells in Ovarian Cancer Angiogenesis.

Ovarian cancer is one of the most common gynecologic malignancies. Recurrence and metastasis often occur after treatment, and it has the highest mortality rate of all gynecological tumors. Cancer stem cells (CSCs) are a small population of cells with the ability of self-renewal, multidirectional differentiation, and infinite proliferation. They have been shown to play an important role in tumor growth, metastasis, drug resistance, and angiogenesis. Ovarian cancer side population (SP) cells, a type of CSC, have been shown to play roles in tumor formation, colony formation, xenograft tumor formation, ascites formation, and tumor metastasis. The rapid progression of tumor angiogenesis is necessary for tumor growth; however, many of the mechanisms driving this process are unclear as is the contribution of CSCs. The aim of this review was to document the current state of knowledge of the molecular mechanism of ovarian cancer stem cells (OCSCs) in regulating tumor angiogenesis.

Nitrogen-Embedding Strategy for Short-Range Charge Transfer Excited States and Efficient Narrowband Deep-Blue Organic Light Emitting Diodes.

The development of deep-blue organic light-emitting diodes (OLEDs) featuring high efficiency and narrowband emission is of great importance for ultrahigh-definition displays with wide color gamut. Herein, based on the nitrogen-embedding strategy for modifying the short range charge transfer excited state energies of multi-resonance (MR) thermally activated delayed fluorescence (TADF) emitters, we introduce one or two nitrogen atoms into the central benzene ring of a versatile boron-embedded 1,3-bis(carbazol-9-yl)benzene skeleton. This approach resulted in the stabilization of the highest occupied molecular orbital energy levels and the formation of intramolecular hydrogen bonds, and thus systematic hypsochromic shifts and narrowing spectra. In toluene solution, two heterocyclic-based MR-TADF molecules, Py-BN and Pm-BN, exhibit deep-blue emissions with high photoluminescence quantum yields of 93 % and 94 %, and narrow full width at half maximum of 14 and 13 nm, respectively. A deep-blue hyperfluorescent OLED based on Py-BN exhibited a maximum external quantum efficiency of 27.7 % and desired color purity with Commission Internationale de L'Eclairage (CIE) coordinates of (0.150, 0.052). These results demonstrate the significant potential for the development of deep blue narrowband MR-TADF emitters.

N-Phenyl-2-Pyridone-Derived Endoperoxide Suppressing both Lung Cancer and Idiopathic Pulmonary Fibrosis Progression by Three-Pronged Action.

We report an endoperoxide compound (E5) which can deliver three therapeutic components by a thermal cycloreversion, namely, singlet oxygen, triplet oxygen and 3-methyl-N-phenyl-2-pyridone (P5), thus targeting multiple mechanisms for treating non-small cell lung cancer and idiopathic pulmonary fibrosis. In aqueous environment, E5 undergoes clean reaction to afford three therapeutic components with a half-life of 8.3 hours without the generation of other by-products, which not only achieves good cytotoxicity toward lung cancer cells and decreases the levels of hypoxia-inducible factor 1α (HIF-1α) protein, but also inhibits the transforming growth factor ß1 (TGF-ß1) induced fibrosis in vitro. In vivo experiments also demonstrated the efficacy of E5 in inhibiting tumor growth and relieving idiopathic pulmonary fibrosis, while exhibiting good biocompatibility. Many lines of evidence reveal the therapeutic efficacy of singlet oxygen and 3-methyl-N-phenyl-2-pyridone for these two lung diseases, and triplet oxygen could downregulate HIF-1α and relieve tumor hypoxia which is a critical issue in photodynamic therapy (PDT). Unlike other combination therapies, in which multiple therapeutic agents are given in independent formulations, our work demonstrates single molecule endoperoxide prodrugs could be developed as new platforms for treatment of cancers and related diseases.

Expression Dynamics Indicate Potential Roles of KIF17 for Nuclear Reshaping and Tail Formation during Spermiogenesis in Phascolosoma esculenta.

Kinesin family member17 (KIF17), a homologous dimer of the kinesin-2 protein family, has important microtubule-dependent and -independent roles in spermiogenesis. Little is known about KIF17 in the mollusk, Phascolosoma esculenta, a newly developed mariculture species in China. Here, we cloned the open reading frame of Pe-kif17 and its related gene, Pe-act, and performed bioinformatics analysis on both. Pe-KIF17 and Pe-ACT are structurally conserved, indicating that they may be functionally conserved. The expression pattern of kif17/act mRNA performed during spermiogenesis revealed their expression in diverse tissues, with the highest expression level in the coelomic fluid of P. esculenta. The expressions of Pe-kif17 and Pe-act mRNA were relatively high during the breeding season (July-September), suggesting that Pe-KIF17/ACT may be involved in spermatogenesis, particularly during spermiogenesis. Further analysis of Pe-kif17 mRNA via fluorescence in situ hybridization revealed the continuous expression of this mRNA during spermiogenesis, suggesting potential functions in this process. Immunofluorescence showed that Pe-KIF17 co-localized with α-tubulin and migrated from the perinuclear cytoplasm to one side of the spermatid, forming the sperm tail. Pe-KIF17 and Pe-ACT also colocalized. KIF17 may participate in spermiogenesis of P. esculenta, particularly in nuclear reshaping and tail formation by interacting with microtubule structures similar to the manchette. Moreover, Pe-KIF17 with Pe-ACT is also involved in nuclear reshaping and tail formation in the absence of microtubules. This study provides evidence for the role of KIF17 during spermiogenesis and provides theoretical data for studies of the reproductive biology of P. esculenta. These findings are important for spermatogenesis in mollusks.