Remodeling Intestinal Microbiota Alleviates Severe Combined Hyperlipidemia-Induced Nonalcoholic Steatohepatitis and Atherosclerosis in LDLR-/- Hamsters.

Combined hyperlipidemia (CHL) manifests as elevated cholesterol and triglycerides, associated with fatty liver and cardiovascular diseases. Emerging evidence underscores the crucial role of the intestinal microbiota in metabolic disorders. However, the potential therapeutic viability of remodeling the intestinal microbiota in CHL remains uncertain. In this study, CHL was induced in low-density lipoprotein receptor-deficient (LDLR-/-) hamsters through an 8-week high-fat and high-cholesterol (HFHC) diet or a 4-month high-cholesterol (HC) diet. Placebo or antibiotics were administered through separate or cohousing approaches. Analysis through 16S rDNA sequencing revealed that intermittent antibiotic treatment and the cohousing approach effectively modulated the gut microbiota community without impacting its overall abundance in LDLR-/- hamsters exhibiting severe CHL. Antibiotic treatment mitigated HFHC diet-induced obesity, hyperglycemia, and hyperlipidemia, enhancing thermogenesis and alleviating nonalcoholic steatohepatitis (NASH), concurrently reducing atherosclerotic lesions in LDLR-/- hamsters. Metabolomic analysis revealed a favorable liver lipid metabolism profile. Increased levels of microbiota-derived metabolites, notably butyrate and glycylglycine, also ameliorated NASH and atherosclerosis in HFHC diet-fed LDLR-/- hamsters. Notably, antibiotics, butyrate, and glycylglycine treatment exhibited protective effects in LDLR-/- hamsters on an HC diet, aligning with outcomes observed in the HFHC diet scenario. Our findings highlight the efficacy of remodeling gut microbiota through antibiotic treatment and cohousing in improving obesity, NASH, and atherosclerosis associated with refractory CHL. Increased levels of beneficial microbiota-derived metabolites suggest a potential avenue for microbiome-mediated therapies in addressing CHL-associated diseases.

Band Engineering of Perovskite Quantum Dot Solids for High-Performance Solar Cells.

CsPbI3 perovskite quantum dot (PQD) shows high potential for next-generation photovoltaics due to their tunable surface chemistry, good solution-processability and unique photophysical properties. However, the remained long-chain ligand attached to the PQD surface significantly impedes the charge carrier transport within the PQD solids, thereby predominantly influencing the charge extraction of PQD solar cells (PQDSCs). Herein, a ligand-induced energy level modulation is reported for band engineering of PQD solids to improve the charge extraction of PQDSCs. Detailed theoretical calculations and systemic experimental studies are performed to comprehensively understand the photophysical properties of the PQD solids dominated by the surface ligands of PQDs. The results reveal that 4-nitrobenzenethiol and 4-methoxybenzenethiol molecules with different dipole moments could firmly anchor to the PQD surface thoroughly the thiol group to modulate the energy levels of PQDs, and a gradient band structure within the PQD solid is subsequently realized. Consequently, the band-engineered PQDSC delivers an efficiency of up to 16.44%, which is one of the highest efficiencies of CsPbI3 PQDSCs. This work provides a feasible avenue for the band engineering of PQD solids by tuning the surface chemistry of PQDs for high-performing solar cells or other optoelectronic devices. This article is protected by copyright. All rights reserved.

Electroacupuncture Inhibits Neural Ferroptosis in Rat Model of Traumatic Brain Injury via Activating System Xc-/GSH/GPX4 Axis.

BACKGROUND: Ferroptosis is an iron-dependent regulating programmed cell death discovered recently that has been receiving much attention in traumatic brain injury (TBI). xCT, a major functional subunit of Cystine/glutamic acid reverse transporter (System Xc-), promotes cystine intake and glutathione biosynthesis, thereby protecting against oxidative stress and ferroptosis. OBJECTIVE: The intention of this research was to verify the hypothesis that electroacupuncture (EA) exerted an anti-ferroptosis effect via an increase in the expression of xCT and activation of the System Xc-/GSH/GPX4 axis in cortical neurons of TBI rats. METHODS: After the TBI rat model was prepared, animals received EA treatment at GV20, GV26, ST36 and PC6, for 15min. The xCT inhibitor Sulfasalazine (SSZ) was administered 2h prior to model being prepared. The degree of neurological impairment was evaluated by means of TUNEL staining and the modified neurological severity score (mNSS). Specific indicators of ferroptosis (Ultrastructure of mitochondria, Iron and ROS) were detected by transmission electron microscopy (TEM), Prussian blue staining (Perls stain) and flow cytometry (FCM), respectively. GSH synthesis and metabolism-related factors in the content of the cerebral cortex were detected by an assay kit. Real-time quantitative PCR (RT-QPCR), Western blot (WB), and immunofluorescence (IF) were used for detecting the expression of System Xc-/GSH/GPX4 axisrelated proteins in injured cerebral cortex tissues. RESULTS: EA successfully relieved nerve damage within 7 days after TBI, significantly inhibited neuronal ferroptosis, upregulated the expression of xCT and System Xc-/GSH/GPX4 axis forward protein and promoted glutathione (GSH) synthesis and metabolism in the injured area of the cerebral cortex. However, aggravation of nerve damage and increased ferroptosis effect were found in TBI rats injected with xCT inhibitors. CONCLUSIONS: EA inhibits neuronal ferroptosis by up-regulated xCT expression and by activating System Xc-/GSH/GPX4 axis after TBI, confirming the relevant theories regarding the EA effect in treating TBI and providing theoretical support for clinical practice.

Evolution of a Restriction Factor by Domestication of a Yeast Retrotransposon.

Transposable elements drive genome evolution in all branches of life. Transposable element insertions are often deleterious to their hosts and necessitate evolution of control mechanisms to limit their spread. The long terminal repeat retrotransposon Ty1 prime (Ty1'), a subfamily of the Ty1 family, is present in many Saccharomyces cerevisiae strains, but little is known about what controls its copy number. Here, we provide evidence that a novel gene from an exapted Ty1' sequence, domesticated restriction of Ty1' relic 2 (DRT2), encodes a restriction factor that inhibits Ty1' movement. DRT2 arose through domestication of a Ty1' GAG gene and contains the C-terminal domain of capsid, which in the related Ty1 canonical subfamily functions as a self-encoded restriction factor. Bioinformatic analysis reveals the widespread nature of DRT2, its evolutionary history, and pronounced structural variation at the Ty1' relic 2 locus. Ty1' retromobility analyses demonstrate DRT2 restriction factor functionality, and northern blot and RNA-seq analysis indicate that DRT2 is transcribed in multiple strains. Velocity cosedimentation profiles indicate an association between Drt2 and Ty1' virus-like particles or assembly complexes. Chimeric Ty1' elements containing DRT2 retain retromobility, suggesting an ancestral role of productive Gag C-terminal domain of capsid functionality is present in the sequence. Unlike Ty1 canonical, Ty1' retromobility increases with copy number, suggesting that C-terminal domain of capsid-based restriction is not limited to the Ty1 canonical subfamily self-encoded restriction factor and drove the endogenization of DRT2. The discovery of an exapted Ty1' restriction factor provides insight into the evolution of the Ty1 family, evolutionary hot-spots, and host-transposable element interactions.

Recombination and repeat-induced point mutation landscapes reveal trade-offs between the sexual and asexual cycles of Magnaporthe oryzae.

The fungal disease caused by Magnaporthe oryzae is one of the most devastating diseases that endanger many crops worldwide. Evidence shows that sexual reproduction can be advantageous for fungal diseases as hybridization facilitates host-jumping. However, the pervasive clonal lineages of M. oryzae observed in natural fields contradict this expectation. A better understanding of the roles of recombination and the fungi-specific repeat-induced point mutation (RIP) in shaping its evolutionary trajectory is essential to bridge this knowledge gap. Here we systematically investigate the RIP and recombination landscapes in M. oryzae using a whole genome sequencing data from 252 population samples and 92 cross progenies. Our data reveal that the RIP can robustly capture the population history of M. oryzae, and we provide accurate estimations of the recombination and RIP rates across different M. oryzae clades. Significantly, our results highlight a parent-of-origin bias in both recombination and RIP rates, tightly associating with their sexual potential and variations of effector proteins. This bias suggests a critical trade-off between generating novel allelic combinations in the sexual cycle to facilitate host-jumping and stimulating transposon-associated diversification of effectors in the asexual cycle to facilitate host coevolution. These findings provide unique insights into understanding the evolution of blast fungus.

Rejuvenating Aged Perovskite Quantum Dots for Efficient Solar Cells.

Perovskite quantum dots (PQDs) have emerged as one of the most promising candidates for next-generation solar cells owing to its remarkable optoelectronic properties and solution processability. However, the optoelectronic properties of PQDs suffer from severe degradation in storage due to the dynamically binding ligands, predominantly affecting photovoltaic applications. Herein, an in situ defect healing treatment (DHT) is reported to effectively rejuvenate aged PQDs. Systematically, experimental studies and theoretical calculations are performed to fundamentally understand the causes leading to the recovered optoelectronic properties of aged PQDs. The results reveal that the I3 - anions produced from tetra-n-octylammonium iodide and iodine could strongly anchor on the surface matrix defects of aged PQDs, substantially diminishing the nonradiative recombination of photogenerated charge carriers. Meanwhile, an DHT could also renovate the morphology of aged PQDs and thus improve the stacking orientation of PQD solids, substantially ameliorating charge carrier transport within PQD solids. Consequently, by using a DHT, the PQD solar cell (PQDSC) yields a high efficiency of up to 15.88%, which is comparable with the PQDSCs fabricated using fresh PQDs. Meanwhile, the stability of PQDSCs fabricated using the rejuvenated PQDs is also largely improved.

CD44 connects autophagy decline and ageing in the vascular endothelium.

The decline of endothelial autophagy is closely related to vascular senescence and disease, although the molecular mechanisms connecting these outcomes in vascular endothelial cells (VECs) remain unclear. Here, we identify a crucial role for CD44, a multifunctional adhesion molecule, in controlling autophagy and ageing in VECs. The CD44 intercellular domain (CD44ICD) negatively regulates autophagy by reducing PIK3R4 and PIK3C3 levels and disrupting STAT3-dependent PtdIns3K complexes. CD44 and its homologue clec-31 are increased in ageing vascular endothelium and Caenorhabditis elegans, respectively, suggesting that an age-dependent increase in CD44 induces autophagy decline and ageing phenotypes. Accordingly, CD44 knockdown ameliorates age-associated phenotypes in VECs. The endothelium-specific CD44ICD knock-in mouse is shorter-lived, with VECs exhibiting obvious premature ageing characteristics associated with decreased basal autophagy. Autophagy activation suppresses the premature ageing of human and mouse VECs overexpressing CD44ICD, function conserved in the CD44 homologue clec-31 in C. elegans. Our work describes a mechanism coordinated by CD44 function bridging autophagy decline and ageing.

XAF1 promotes anti-RNA virus immune responses by regulating chromatin accessibility.

A rapid induction of antiviral genes is critical for eliminating viruses, which requires activated transcription factors and opened chromatins to initiate transcription. However, it remains elusive how the accessibility of specific chromatin is regulated during infection. Here, we found that XAF1 functioned as an epigenetic regulator that liberated repressed chromatin after infection. Upon RNA virus infection, MAVS recruited XAF1 and TBK1. TBK1 phosphorylated XAF1 at serine-252 and promoted its nuclear translocation. XAF1 then interacted with TRIM28 with the guidance of IRF1 to the specific locus of antiviral genes. XAF1 de-SUMOylated TRIM28 through its PHD domain, which led to increased accessibility of the chromatin and robust induction of antiviral genes. XAF1-deficient mice were susceptible to RNA virus due to impaired induction of antiviral genes. Together, XAF1 acts as an epigenetic regulator that promotes the opening of chromatin and activation of antiviral immunity by targeting TRIM28 during infection.

Reproducible evaluation of transposable element detectors with McClintock 2 guides accurate inference of Ty insertion patterns in yeast.

BACKGROUND: Many computational methods have been developed to detect non-reference transposable element (TE) insertions using short-read whole genome sequencing data. The diversity and complexity of such methods often present challenges to new users seeking to reproducibly install, execute, or evaluate multiple TE insertion detectors. RESULTS: We previously developed the McClintock meta-pipeline to facilitate the installation, execution, and evaluation of six first-generation short-read TE detectors. Here, we report a completely re-implemented version of McClintock written in Python using Snakemake and Conda that improves its installation, error handling, speed, stability, and extensibility. McClintock 2 now includes 12 short-read TE detectors, auxiliary pre-processing and analysis modules, interactive HTML reports, and a simulation framework to reproducibly evaluate the accuracy of component TE detectors. When applied to the model microbial eukaryote Saccharomyces cerevisiae, we find substantial variation in the ability of McClintock 2 components to identify the precise locations of non-reference TE insertions, with RelocaTE2 showing the highest recall and precision in simulated data. We find that RelocaTE2, TEMP, TEMP2 and TEBreak provide consistent estimates of [Formula: see text]50 non-reference TE insertions per strain and that Ty2 has the highest number of non-reference TE insertions in a species-wide panel of [Formula: see text]1000 yeast genomes. Finally, we show that best-in-class predictors for yeast applied to resequencing data have sufficient resolution to reveal a dyad pattern of integration in nucleosome-bound regions upstream of yeast tRNA genes for Ty1, Ty2, and Ty4, allowing us to extend knowledge about fine-scale target preferences revealed previously for experimentally-induced Ty1 insertions to spontaneous insertions for other copia-superfamily retrotransposons in yeast. CONCLUSION: McClintock ( https://github.com/bergmanlab/mcclintock/ ) provides a user-friendly pipeline for the identification of TEs in short-read WGS data using multiple TE detectors, which should benefit researchers studying TE insertion variation in a wide range of different organisms. Application of the improved McClintock system to simulated and empirical yeast genome data reveals best-in-class methods and novel biological insights for one of the most widely-studied model eukaryotes and provides a paradigm for evaluating and selecting non-reference TE detectors in other species.

Comparison of the outcome after anterior cervical ossified posterior longitudinal ligament en bloc resection versus posterior total laminectomy and fusion in patients with ossification of the cervical posterior longitudinal ligament: a prospective randomized controlled trial.

The optimal procedure for the treatment of ossification of the posterior longitudinal ligament (OPLL) remains controversial. The aim of this study was to compare the outcome of anterior cervical ossified posterior longitudinal ligament en bloc resection (ACOE) with posterior laminectomy and fusion with bone graft and internal fixation (PTLF) for the surgical management of patients with this condition. Between July 2017 and July 2019, 40 patients with cervical OPLL were equally randomized to undergo surgery with an ACOE or a PTLF. The clinical and radiological results were compared between the two groups. The Japanese Orthopaedic Association (JOA) score and recovery rate in the ACOE group were significantly higher than those in the PTLF group during two years postoperatively, provided that the canal occupying ratio (COR) was > 50%, or the K-line was negative. There was no significant difference in JOA scores and rate of recovery between the two groups in those in whom the COR was < 50%, or the K-line was positive. There was no significant difference in the Cobb angle between C2 and C7, sagittal vertical axis, cervical range of motion (ROM), and complications between the two groups. Compared with PTLF, ACOE is a preferred surgical approach for the surgical management of patients with cervical OPLL in that it offers a better therapeutic outcome when the COR is > 50%, or the K-line is negative, and it also preserves better cervical curvature and sagittal balance. The prognosis of ACOE is similar to that of PTLE when the COR is < 50%, or the K-line is positive.

Reproducible evaluation of transposable element detectors with McClintock 2 guides accurate inference of Ty insertion patterns in yeast.

BACKGROUND: Many computational methods have been developed to detect non-reference transposable element (TE) insertions using short-read whole genome sequencing data. The diversity and complexity of such methods often present challenges to new users seeking to reproducibly install, execute, or evaluate multiple TE insertion detectors. RESULTS: We previously developed the McClintock meta-pipeline to facilitate the installation, execution, and evaluation of six first-generation short-read TE detectors. Here, we report a completely re-implemented version of McClintock written in Python using Snakemake and Conda that improves its installation, error handling, speed, stability, and extensibility. McClintock 2 now includes 12 short-read TE detectors, auxiliary pre-processing and analysis modules, interactive HTML reports, and a simulation framework to reproducibly evaluate the accuracy of component TE detectors. When applied to the model microbial eukaryote Saccharomyces cerevisiae, we find substantial variation in the ability of McClintock 2 components to identify the precise locations of non-reference TE insertions, with RelocaTE2 showing the highest recall and precision in simulated data. We find that RelocaTE2, TEMP, TEMP2 and TEBreak provide a consistent and biologically meaningful view of non-reference TE insertions in a species-wide panel of ∻1000 yeast genomes, as evaluated by coverage-based abundance estimates and expected patterns of tRNA promoter targeting. Finally, we show that best-in-class predictors for yeast have sufficient resolution to reveal a dyad pattern of integration in nucleosome-bound regions upstream of yeast tRNA genes for Ty1, Ty2, and Ty4, allowing us to extend knowledge about fine-scale target preferences first revealed experimentally for Ty1 to natural insertions and related copia-superfamily retrotransposons in yeast. CONCLUSION: McClintock (https://github.com/bergmanlab/mcclintock/) provides a user-friendly pipeline for the identification of TEs in short-read WGS data using multiple TE detectors, which should benefit researchers studying TE insertion variation in a wide range of different organisms. Application of the improved McClintock system to simulated and empirical yeast genome data reveals best-in-class methods and novel biological insights for one of the most widely-studied model eukaryotes and provides a paradigm for evaluating and selecting non-reference TE detectors for other species.

Electrically driven supersymmetric semiconductor laser arrays with single-lobe far-field patterns.

Semiconductor laser arrays based on the third-order supersymmetric (SUSY) transformation are proposed to increase the mode discrimination between fundamental supermode and high-order supermodes. The distance between the edge waveguide of the main array and that of the superpartners is optimized. Then, the electric field distributions of different modes are also calculated, which show that, except for the fundamental supermode, the high-order supermodes penetrate deeper into the superpartner arrays, which accounts for the increased loss of high-order supermodes. The fabricated third-order SUSY laser array can emit light with a single-lobe far-field pattern under an injection current of 70 mA, which is a promising candidate for optical couplings between lasers and optical elements.

Antisolvent-Assisted In Situ Cation Exchange of Perovskite Quantum Dots for Efficient Solar Cells.

Cesium-formamidinium lead iodide perovskite quantum dots (FAx Cs1- x PbI3 PQDs) show high potential for next-generation photovoltaics due to their outstanding optoelectronic properties. However, achieving composition-tunable hybrid PQDs with desirable charge transport remains a significant challenge. Herein, by leveraging an antisolvent-assisted in situ cation exchange of PQDs, homogeneous FAx Cs1- x PbI3 PQDs with controllable stoichiometries and surface ligand chemistry are realized. Meanwhile, the crystallographic stability of PQDs is substantially improved by substituting the cations of the PQDs mediated by surface vacancies. Consequently, PQD solar cell delivers an efficiency of 17.29%, the highest value among the homostructured PQD solar cells. The high photovoltaic performance is attributed to the broadened light harvesting spectra, flattened energy landscape, and rationalized energy levels of highly oriented PQD solids, leading to efficient charge carrier extraction. This work provides a feasible approach for the stoichiometry regulation of PQDs to finely tailor the optoelectronic properties and tolerance factors of PQDs toward high-performing photovoltaics.

Plastome evolution and phylogenomics of Impatiens (Balsaminaceae).

MAIN CONCLUSION: This study reported seven new plastomes from Impatiens and observed three highly variable regions for phylogeny and DNA barcoding, which resolved the relationships among sections of subgenus Impatiens. Impatiens L. (Balsaminaceae, Ericales) is one of the largest and most diverse genera of angiosperms, widely known for its taxonomic difficulty. In this study, we reevaluated the infrageneric relationships within the genus Impatiens, using complete plastome sequence data. Seven complete plastomes of Impatiens (representing 6 species) were newly sequenced and characterized along with 20 previously published plastomes of other Impatiens species, plus 2 plastomes of outgroups (Hydrocera triflora, Balsaminaceae; Marcgravia coriacea, Marcgraviaceae). The total size of these 29 plastomes ranged from 151,538 bp to 152,917 bp, except 2 samples of Impatiens morsei, which exhibited a shorter length and lost some genes encoding NADH dehydrogenase subunits. Moreover, the number of simple sequence repeats (SSRs) ranged from 51 to 113, and the number of long repeats from 17 to 26. In addition, three highly variable regions were identified (trnG-GCC (The previous one), ndhF-rpl32-trnL-UGA-ccsA, and ycf1). Our phylogenomic analysis based on 80 plastome-derived protein-coding genes strongly supported the monophyly of Impatiens and its two subgenera (Clavicarpa and Impatiens), and fully resolved relationships among the six (out of seven) sampled sections of subgenus Impatiens. Overall, the plastome DNA markers and phylogenetic results reported in this study will facilitate future identification, taxonomic and DNA barcoding studies in Impatiens as well as evolutionary studies in Balsaminaceae.

Horizontal transfer and recombination fuel Ty4 retrotransposon evolution in Saccharomyces.

Horizontal transposon transfer (HTT) plays an important role in the evolution of eukaryotic genomes, however the detailed evolutionary history and impact of most HTT events remain to be elucidated. To better understand the process of HTT in closely-related microbial eukaryotes, we studied Ty4 retrotransposon subfamily content and sequence evolution across the genus Saccharomyces using short- and long-read whole genome sequence data, including new PacBio genome assemblies for two S. mikatae strains. We find evidence for multiple independent HTT events introducing the Tsu4 subfamily into specific lineages of S. paradoxus, S. cerevisiae, S. eubayanus, S. kudriavzevii and the ancestor of the S. mikatae/S. jurei species pair. In both S. mikatae and S. kudriavzevii, we identified novel Ty4 clades that were independently generated through recombination between resident and horizontally-transferred subfamilies. Our results reveal that recurrent HTT and lineage-specific extinction events lead to a complex pattern of Ty4 subfamily content across the genus Saccharomyces. Moreover, our results demonstrate how HTT can lead to coexistence of related retrotransposon subfamilies in the same genome that can fuel evolution of new retrotransposon clades via recombination.

CUR5g, a novel autophagy inhibitor, exhibits potent synergistic anticancer effects with cisplatin against non-small-cell lung cancer.

Autophagy, a highly conserved degradation process of eukaryotic cells, has been proven to be closely related to chemoresistance and metastasis of non-small-cell lung cancer (NSCLC). Autophagy inhibitors, such as chloroquine (CQ) and its derivative hydroxychloroquine (HCQ), has been shown to mediate anticancer effects in preclinical models, especially when combined with chemotherapy. However, the vast majority of autophagy inhibitors, including CQ and HCQ, actually disrupt lysosomal or/and possibly non-lysosomal processes other than autophagy. It is therefore of great significance to discover more specific autophagy inhibitors. In this study, after screening a series of curcumin derivatives synthesized in our laboratory, we found that (3E,5E)-1-methyl-3-(4-hydroxybenzylidene)-5-(3-indolymethylene)-piperidine-4-one (CUR5g) selectively inhibited autophagosome degradation in cancer cells by blocking autophagosome-lysosome fusion. CUR5g did not affect the lysosomal pH and proteolytic function, nor did it disturb cytoskeleton. CUR5g blocked the recruitment of STX17, a soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein, to autophagosomes via a UVRAG-dependent mechanism, resulting in the inability of autophagosomes to fuse with lysosomes. CUR5g alone did not induce apoptosis and necrosis of A549 cells, but significantly inhibited the mobility and colony formation of A549 cells. More excitingly, CUR5g showed no obvious toxicity to normal HUVECs in vitro or mice in vivo. CUR5g enhances the cisplatin sensitivity of A549 cells and effectively inhibited autophagy in tumor tissues in vivo. Collectively, our study identified a new late-stage autophagy inhibitor and provided a novel option for NSCLC treatment, particular when combined with cisplatin.

Different phases in non-Hermitian topological semiconductor stripe laser arrays.

As a novel branch of topology, non-Hermitian topological systems have been extensively studied in theory and experiments recently. Topological parity-time (PT)-symmetric semiconductor stripe laser arrays based on the Su-Schreiffer-Heeger model are proposed. The degree of non-Hermicity can be tuned by altering the length of the cavities, and PT symmetry can be realized by patterned electrode. Three laser arrays working in different non-Hermitian phases are analyzed and fabricated. With the increasing degree of non-Hermicity, the peaks of output intensities move from the edge to the bulk. The proposed semiconductor stripe laser array can function as an active, flexible, and feasible platform to investigate and explore non-Hermitian topology for further developments in this field.

High-brightness and high-efficiency diode laser module based on double wavelength division multiplexing external cavities.

In this Letter, a new, to the best of our knowledge, external cavity structure based on double wavelength division multiplexing external cavities is proposed and demonstrated. The electro-optical conversion efficiency is improved and the brightness of the spectral beam combining diode lasers is enhanced. One wavelength division multiplexing external cavity is placed on the rear-side of the laser emitters to provide the strong optical feedback for wavelength locking and the other wavelength division multiplexing external cavity is placed on the front-side of laser emitters to combine three emitter beams to one beam. A maximum output power of up to 7.5 W is obtained and the brightness of the laser diode is 100 MW cm-2 sr-1 with an electro-optical conversion efficiency of 46.5%. Compared with a standard cavity for spectral beam combining, the use of double wavelength division multiplexing external cavities results in an electro-optical conversion efficiency improvement of 6.5%. The whole structure provides a new technology to achieve high-brightness and high electro-optical conversion efficiency for a laser diode source.

Discovery of novel Quinazoline-based KRAS G12C inhibitors as potential anticancer agents.

A series of novel quinazoline analogs were designed and synthesized based on ARS-1620 and LLK-10 (a KRAS inhibitor reported by us recently) as KRAS G12C inhibitors with a 5-nitrofuran-2-carboxylic acid warhead. Most of the newly synthesized compounds exhibited antiproliferative activities similar to or better than ARS-1620 and LLK-10. Among them, compound KS-19 showed the highest activity (IC50 = 460 âˆ¼ 870 nM) and reasonable selectivity (3 to 27-fold) for inhibiting the proliferation of KRAS G12C-mutated cells (NCI-H358 and NCI-H23) over other KRAS mutant (e.g. G13D, G12D, G12S, G12V, WT) cancer cells. ITC, KRAS-GTP pull-down assay and western blot analysis demonstrated that KS-19 could bind to KRAS G12C protein with high affinity (KD = 97 nM), thus decreasing the active form of KRAS G12C (KRAS G12C-GTP) and phosphorylated Erk, and leading to NCI-H358 tumor cell apoptosis. In addition, KS-19 was able to suppress the formation of NCI-H358 and NCI-H23 tumor colonies in a dose-dependent manner. Moreover, in vivo efficacy studies indicated that KS-19 (40 mg/kg) was effective in suppressing tumor growth in nude mice bearing NCI-H358 tumor xenografts with a TGI (tumor growth inhibition) of 47 %, comparable to that of ARS-1620 (50 %). Lastly, KS-19 possessed a benign toxicity profile without causing bone marrow suppression and any obvious morphological abnormalities in major organs of mice. Collectively, these results suggest that KS-19 represents a novel inhibitor of KRAS G12C worthy of further investigation as a potential anticancer agent.

Highly Orientated Perovskite Quantum Dot Solids for Efficient Solar Cells.

Perovskite quantum dots (PQDs) have emerged as competitive optoelectronic materials for photovoltaic applications due to their ideal bandgap energy, high defect tolerance, and solution processability. However, the highly dynamic surface and imperfect cubic structure of PQDs generally result in unfavorable charge-carrier transport within the PQD solids and serious nonradiative recombination. Herein, a highly orientated PQD solid is demonstrated using precursor engineering accompanied by a chemical stripping treatment (CST). A combination of systematic experimental studies and theoretical calculations is conducted to fundamentally understand the resurfacing of PQDs using the CST approach. The results reveal that the highly ordered PQDs can result in a high orientation of PQD solids, significantly promoting charge-carrier transport within the PQD solids. Meanwhile, the ideal cubic-structured PQD with an iodine-rich surface dramatically decreases surface trap states, thereby substantially diminishing trap-assisted nonradiative recombination. Consequently, the inorganic PQD solar cell delivers a power conversion efficiency of up to 16.25%. This work provides a feasible avenue to construct highly orientated PQD solids with improved photophysical properties for high-performance optoelectronic devices.