Polarization switching in a mid-infrared Er:YAlO3 laser.

We report on a polarization-resolved study of mid-infrared emission properties of Er3+-doped orthorhombic yttrium aluminum perovskite YAlO3 single crystal. For the 4I11/2 → 4I13/2 Er3+ transition, the stimulated emission cross section is 0.20 × 10-20 cm2 at 2919 nm for light polarization E ‖ c. Pumped by an Yb-fiber laser at 976 nm, the 10 at.% Er:YAlO3 laser delivered 1.36 W at 2919 nm with a slope efficiency of 31.4%, very close to the Stokes limit, a laser threshold as low as 33 mW and a linear polarization. Pump-induced polarization switching between E || b and E || c eigen states was observed and explained by excited-state absorption from the terminal laser level.

RNA-dependent RNA polymerases regulate ascospore discharge through the exonic-sRNA-mediated RNAi pathway.

Ascospores, forcibly released into the air from perithecia, are the primary inoculum for Fusarium head blight. In Fusarium graminearum, the biological functions of four RNA-dependent RNA polymerases (RdRPs) (Fgrdrp1-4) have been reported, but their regulatory mechanisms are poorly understood and the function of Fgrdrp5 is still unknown. In this study, we found that in addition to Fgrdrp1 and Fgrdrp2, Fgrdrp5 also plays an important role in ascospore discharge, and they all participate in the generation of turgor pressure in a polyol-dependent manner. Moreover, these three genes all affect the maturation of ascospores. Deep sequencing and co-analysis of small RNA and mRNA certified that Fgrdrp1, Fgrdrp2, and Fgrdrp5 partly share their functions in the biogenesis and accumulation of exonic small interference RNA (ex-siRNA), and these three RdRPs negatively regulate the expression levels of ex-siRNA corresponding genes, including certain genes associated with ascospore development or discharge. Furthermore, the differentially expressed genes of deletion mutants, those involved in lipid and sugar metabolism or transport as well as sexual development-related transcription factors, may also contribute to the defects in ascospore maturation or ascospore discharge. In conclusion, our study suggested that the components of the dicer-dependent ex-siRNA-mediated RNA interference pathway include at least Fgrdrp1, Fgrdrp2, and Fgrdrp5. IMPORTANCE: We found that in addition to Fgrdrp1 and Fgrdrp2, Fgrdrp5 also plays important roles in ascospore maturation and ascospore discharge of Fusarium graminearum. These three RNA-dependent RNA polymerases participate in the biogenesis and accumulation of exonic small interference RNA and then regulate ascospore discharge.

Enhancing Energy Harvesting Efficiency of Flapping Wings with Leading-Edge Magnus Effect Cylinder.

According to the Magnus principle, a rotating cylinder experiences a lateral force perpendicular to the incoming flow direction. This phenomenon can be harnessed to boost the lift of an airfoil by positioning a rotating cylinder at the leading edge. In this study, we simulate flapping-wing motion using the sliding mesh technique in a heaving coordinate system to investigate the energy harvesting capabilities of Magnus effect flapping wings (MEFWs) featuring a leading-edge rotating cylinder. Through analysis of the flow field vortex structure and pressure distribution, we explore how control parameters such as gap width, rotational speed ratio, and phase difference of the leading-edge rotating cylinder impact the energy harvesting characteristics of the flapping wing. The results demonstrate that MEFWs effectively mitigate the formation of leading-edge vortices during wing motion. Consequently, this enhances both lift generation and energy harvesting capability. MEFWs with smaller gap widths are less prone to induce the detachment of leading-edge vortices during motion, ensuring a higher peak lift force and an increase in the energy harvesting efficiency. Moreover, higher rotational speed ratios and phase differences, synchronized with wing motion, can prevent leading-edge vortex generation during wing motion. All three control parameters contribute to enhancing the energy harvesting capability of MEFWs within a certain range. At the examined Reynolds number, the optimal parameter values are determined to be a∗ = 0.0005, R = 3, and ϕ0 = 0°.

Fruquintinib-induced renal-limited thrombotic microangiopathy: a case report.

BACKGROUND: Fruquintinib is a highly selective inhibitor of vascular endothelial growth factor receptor (VEGFR). Currently, there are no reported cases of fruquintinib causing kidney-restrictive thrombotic microangiopathy (TMA) in the available Chinese and foreign literature. CASE PRESENTATION: In this case report, we presented a 73-year-old patient receiving fruquintinib for metastatic colon cancer, manifesting abundant proteinuria, in which kidney-restrictive TMA was also diagnosed through renal biopsy. As far as we were concerned, this was the frst reported in terms of fruquintinib-induced kidney-restrictive TMA confrmed by renal biopsy. CONCLUSION: This case indicates that fruquintinib may result in kidney-restrictive TMA, which is a rare but life-threatening complication of cancer treatment drug. Therefore, regular monitoring of proteinuria and blood pressure is imperative for all patients undergoing anti-VEGF drug therapy. And renal biopsy should be promptly conducted to facilitate early detection of thrombotic microangiopathy.

Controlled release of vitamin A palmitate from crosslinked cyclodextrin organic framework for dry eye disease therapy.

Controlled release drug delivery systems of eye drops are a promising ophthalmic therapy with advantages of good patient compliance and low irritation. However, the lack of a suitable drug carrier for ophthalmic use limits the development of the aforementioned system. Herein, the crosslinked cyclodextrin organic framework (COF) with a cubic porous structure and a uniform particle size was synthesized and applied to solidify vitamin A palmitate (VAP) by using the solvent-free method. The VAP@COF suspension eye drops were formulated by screening co-solvents, suspending agents, and stabilizing agents to achieve a homogeneous state and improve stability. According to the in vitro release study, the VAP@COF suspension exhibited a controlled release of VAP within 12 h. Both the ex vivo corneal contact angle and in vivo fluorescence tracking indicated that the VAP@COF suspension prolonged the VAP residence time on the ocular surface. This suspension accelerated the recovery of the dry eye disease (DED) model in New Zealand rabbits. Furthermore, the suspension was non-cytotoxic to human corneal epithelial cells and non-irritation to rabbit eyes. In summary, the particulate COF is an eye-acceptable novel carrier that sustains release and prolongs the VAP residence time on the ocular surface for DED treatment.

An effector SsCVNH promotes the virulence of Sclerotinia sclerotiorum through targeting class III peroxidase AtPRX71.

Many plant pathogens secrete effector proteins into the host plant to suppress host immunity and facilitate pathogen colonization. The necrotrophic pathogen Sclerotinia sclerotiorum causes severe plant diseases and results in enormous economic losses, in which secreted proteins play a crucial role. SsCVNH was previously reported as a secreted protein, and its expression is significantly upregulated at 3 h after inoculation on the host plant. Here, we further demonstrated that deletion of SsCVNH leads to attenuated virulence. Heterologous expression of SsCVNH in Arabidopsis enhanced pathogen infection, inhibited the host PAMP-triggered immunity (PTI) response and increased plant susceptibility to S. sclerotiorum. SsCVNH interacted with class III peroxidase AtPRX71, a positive regulator of innate immunity against plant pathogens. SsCVNH could also interact with other class III peroxidases, thus reducing peroxidase activity and suppressing plant immunity. Our results reveal a new infection strategy employed by S. sclerotiorum in which the fungus suppresses the function of class III peroxidases, the major component of PTI to promote its own infection.

The Identification of RPL4 as a Hub Gene Associated with Goat Litter Size via Weighted Gene Co-Expression Network Analysis.

Reproduction in goats is a highly complex and dynamic process of life regulation, involving coordinated regulation from various aspects such as central nervous system regulation, reproductive system development, oocyte maturation, and fertilized egg development. In recent years, researchers have identified numerous genes associated with goat reproductive performance through high-throughput sequencing, single-cell sequencing, gene knockout, and other techniques. However, there is still an urgent need to explore marker genes related to goat reproductive performance. In this study, a single-cell RNA sequencing dataset of oocytes (GSE136005) was obtained from the Gene Expression Omnibus (GEO) database. Weighted Gene Co-expression Network Analysis (WGCNA) was utilized to identify modules highly correlated with goat litter size. Through gene function enrichment analysis, it was found that genes within the modules were mainly enriched in adhesive junctions, cell cycle, and other signaling pathways. Additionally, the top 30 hub genes with the highest connectivity in WGCNA were identified. Subsequently, using Protein-Protein Interaction (PPI) network analysis, the top 30 genes with the highest connectivity within the modules were identified. The intersection of hub genes, key genes in the PPI network, and differentially expressed genes (DEGs) led to the identification of the RPL4 gene as a key marker gene associated with reproductive capacity in goat oocytes. Overall, our study reveals that the RPL4 gene in oocytes holds promise as a biological marker for assessing goat litter size, deepening our understanding of the regulatory mechanisms underlying goat reproductive performance.

[Chemical constituents and pharmacological effects of Nauclea officinalis and predictive analysis of its quality markers].

Nauclea officinalis is a Chinese medicinal material with a high medicinal value, which contains various chemical constituents such as alkaloids, pentacyclic triterpenoids and their saponins, organic phenolic acids and their glycosides, iridoids, and flavonoids. It has antiviral, antibacterial, antipyretic, analgesic, anti-inflammatory, and immunoregulatory functions. This article systematically reviewed the reported chemical constituents and pharmacological effects of N. officinalis. According to the concept of quality markers, the quality markers of N. officinalis were predicted and analyzed from the aspects of plant kinship, specificity of chemical constituents, traditional drug efficacy, measurability of chemical constituents, plasma components, and different producing areas and harvest times, in order to provide a basis for the quality evaluation of N. officinalis.

What influences the performance of carbon emissions in China?-Research on the inter-provincial carbon emissions' conditional configuration impacts.

The severe global warming issue currently threatens humans' existence and development. Countries and international organizations have effectively implemented policies to reduce carbon emissions and investigate low-carbon growth strategies. Reducing carbon emissions is a hot topic that academics and government policy-making departments are concerned about.Through necessary condition analysis (NCA) and fuzzy set qualitative comparative analysis(fsQCA), this paper investigates local governments' configuration linkage effect and path choice to improve carbon emission performance from six dimensions: energy consumption, industrial structure, technological innovation, government support, economic development, and demographic factors. The research findings include the following: (1) Individual condition does not represent necessary conditions for the government's carbon performance. Among the two sets of second-order equivalence configurations(S and Q) (five high-level carbon performance configurations), those dominated by economic development or low energy consumption can produce high-level carbon performance. Therefore, the six antecedent conditions dimensions work together to explain how the government can create high levels of carbon performance. (2)According to the regional comparison, China's eastern, central, and western regions exhibit similarities and differences in the driving forces behind high carbon emission performance. All three regions can demonstrate carbon emission performance when all the factors are combined. However, when constrained by the conditions of each region's resource endowment, the eastern region emphasizes the advantage of economic and technological innovation, the central region favors government support and demographic factors, and the western region prefers upgrading industrial structure based on a specific level of economic development.

Nanostructured lipid carriers loaded with morellic acid for enhanced anticancer efficacy: preparation, characterization, pharmacokinetics and anticancer evaluation.

Morellic acid (MA), a typical compound found in Garcinia plants, is known for its anticancer properties. In present study, we isolated MA from resin of Garcinia hanburyi Hook. f. using preparative chromatography. We have successfully prepared MA-loaded nanostructured lipid carriers (MA-NLCs) and refined the production process via orthogonal testing. Optimization of the preparation process resulted in an average particle size of 165.50±1.70 nm with a PDI of 0.19±0.01. The EE% and DL% of MA-NLCs were 78.17±0.34% and 7.25±0.38%, respectively. The zeta potential of MA-NLCs was -21.85±0.67 mV. Comparatively, MA-NLCs showed a greater area under the curve (AUC) and an extended half-life (t1/2) than free MA. Pharmacokinetics analysis revealed that the AUC0-t increased from 4.91±0.65 µg/mL∙min (free MA) to 18.91±3.40 µg/mL∙min (MA-NLCs) and the t1/2 value for MA-NLCs was 7.93-fold longer than that of free MA. In vitro cytotoxic assessments indicated that MA formulations curtailed the proliferation of cancer cells. In vivo, MA-NLCs significantly inhibited the tumor growth in tumor-bearing mouse model. Molecular mechanism studies revealed that up-regulation of apaf-1 and activation of caspase-3, caspase-9 and GSDME by MA-NLCs may trigger to apoptosis and pyroptosis in cancer cells. Consequently, our findings support the potential of NLCs as an effective MA delivery system for the clinical management of cancer.

Machine learning and new insights for breast cancer diagnosis.

Breast cancer (BC) is the most prominent form of cancer among females all over the world. The current methods of BC detection include X-ray mammography, ultrasound, computed tomography, magnetic resonance imaging, positron emission tomography and breast thermographic techniques. More recently, machine learning (ML) tools have been increasingly employed in diagnostic medicine for its high efficiency in detection and intervention. The subsequent imaging features and mathematical analyses can then be used to generate ML models, which stratify, differentiate and detect benign and malignant breast lesions. Given its marked advantages, radiomics is a frequently used tool in recent research and clinics. Artificial neural networks and deep learning (DL) are novel forms of ML that evaluate data using computer simulation of the human brain. DL directly processes unstructured information, such as images, sounds and language, and performs precise clinical image stratification, medical record analyses and tumour diagnosis. Herein, this review thoroughly summarizes prior investigations on the application of medical images for the detection and intervention of BC using radiomics, namely DL and ML. The aim was to provide guidance to scientists regarding the use of artificial intelligence and ML in research and the clinic.

Ribosomal S6 kinase 2-forkhead box protein O4 signaling pathway plays an essential role in melanogenesis.

Although previous studies have examined the signaling pathway involved in melanogenesis through which ultraviolet (UV) or α-melanocyte-stimulating hormones (α-MSH) stimuli act as key inducers to produce melanin at the stratum basal layer of the epidermis, the signaling pathway regulating melanogenesis is still controversial. This study reports that α-MSH, not UVA and UVB, acted as a major stimulus of melanogenesis in B16F10 melanoma cells. Signaling pathway analysis using gene knockdown technology and chemical inhibitors, the mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK)/p90 ribosomal S6 kinase 2 (RSK2) played an important role in melanogenesis. Unexpectedly, LY294002, a PI3K inhibitor, increased melanogenesis without UV or α-MSH stimulation, suggesting that the PI3K/AKT signaling pathway may not be a major signaling pathway for melanogenesis. Chemical inhibition of the MEKs/ERKs/RSK2 signaling pathway using U0126 or BI-D1870 suppressed melanogenesis by stimulation of UVA or α-MSH stimulation, or both. In particular, the genetic depletion of RSK2 or constitutive active (CA)-RSK2 overexpression showed that RSK2 plays a key role in melanogenesis. Interestingly, forkhead box protein O4 (FOXO4) was phosphorylated by RSK2, resulting in the increase of FOXO4's transactivation activity. Notably, the FOXO4 mutant harboring serine-to-alanine replacement at the phosphorylation sites totally abrogated the transactivation activity and reduced melanin production, indicating that RSK2-mediated FOXO4 activity plays a key role in melanogenesis. Furthermore, kaempferol, a flavonoid inhibiting the RSK2 activity, suppressed melanogenesis. In addition, FOXO4-wt overexpression showed that FOXO4 enhance melanin synthesis. Overall, the RSK2-FOXO4 signaling pathway plays a key role in modulating melanogenesis.

Dysregulated CREB3 cleavage at the nuclear membrane induces karyoptosis-mediated cell death.

Cancer cells often exhibit resistance to apoptotic cell death, but they may be vulnerable to other types of cell death. Elucidating additional mechanisms that govern cancer cell death is crucial for developing new therapies. Our research identified cyclic AMP-responsive element-binding protein 3 (CREB3) as a crucial regulator and initiator of a unique cell death mechanism known as karyoptosis. This process is characterized by nuclear shrinkage, deformation, and the loss of nuclear components following nuclear membrane rupture. We found that the N-terminal domain (aa 1-230) of full-length CREB3 (CREB3-FL), which is anchored to the nuclear inner membrane (INM), interacts with lamins and chromatin DNA. This interaction maintains a balance between the outward force exerted by tightly packed DNA and the inward constraining force, thereby preserving INM integrity. Under endoplasmic reticulum (ER) stress, aberrant cleavage of CREB3-FL at the INM leads to abnormal accumulation of the cleaved form of CREB3 (CREB3-CF). This accumulation disrupts the attachment of CREB3-FL to the INM, resulting in sudden rupture of the nuclear membrane and the onset of karyoptosis. Proteomic studies revealed that CREB3-CF overexpression induces a DNA damage response akin to that caused by UVB irradiation, which is associated with cellular senescence in cancer cells. These findings demonstrated that the dysregulation of CREB3-FL cleavage is a key factor in karyoptotic cell death. Consequently, these findings suggest new therapeutic strategies in cancer treatment that exploit the process of karyoptosis.

Biological Control of Rapeseed Clubroot (Plasmodiophora brassicae) using the Endophytic Fungus Didymella macrostoma P2.

Didymella macrostoma P2 was isolated from rapeseed (Brassica napus), and it is an endophyte of rapeseed and an antagonist of three rapeseed pathogens, Botrytis cinerea, Leptosphaeria biglobosa and Sclerotinia sclerotiorum. However, whether or not P2 has a suppressive effect on infection of rapeseed by the clubroot pathogen Plasmodiophora brassicae remains unknown. This study was conducted to detect production of antimicrobials by P2 and to determine efficacy of the antimicrobials and P2 pycnidiospores in suppression of rapeseed clubroot. Results showed that cultural filtrates (CF) of P2 in potato dextrose broth and the substances in pycnidiospore mucilages exuded from P2 pycnidia were inhibitory to P. brassicae. In the indoor experiment, seeds of the susceptible rapeseed cultivar Zhongshuang No.9 treated with P2 CF and the P2 spore suspension (P2 SS, 1 × 107 spores/ml) reduced clubroot severity by 31% to 70% on the 30-day-old seedlings compared to the control (seeds treated with water). P2 was re-isolated from the roots of the seedlings in the treatment of P2 SS, the average isolation frequency in the healthy roots (26%) was much higher than that (5%) in the diseased roots. In the field experiment, seeds of another susceptible rapeseed cultivar Huayouza 50 (HYZ50) treated with P2 CF, P2 CE (chloroform extract of P2 CF, 30 µg/ml) and P2 SS reduced clubroot severity by 29% to 48% on 60-day-old seedlings and by 28% to 59% on adult plants (220 days old) compared to the control treatment. The three P2 treatments on HYZ50 produced significantly (P < 0.05) higher seed yield than the control treatment on this rapeseed cultivar, and they even generated seed yield similar to that produced by the resistant rapeseed cultivar Shengguang 165R in one of the two seasons. These results suggest that D. macrostoma P2 is an effective biocontrol agent against rapeseed clubroot.

Energy scaling of a narrowband, periodically poled LiNbO3, nanosecond, nonresonant optical parametric oscillator.

We demonstrate that 3-mm-thick, periodically poled L i N b O 3 enables energy scaling of a nonresonant optical parametric oscillator operated in the narrowband mode with a volume Bragg grating at the signal wavelength. Utilizing the full available pump power at 1064 nm, we obtained maximum average powers of 2.25 and 2.08 W for the signal (1.922 µm) and idler (2.383 µm) pulses at 10 kHz, at a total conversion efficiency of 32.8%, which represents a fourfold increase in terms of peak powers over our previous work. The signal and idler spectral linewidths were ∼1n m, with pulse lengths of ∼6n s and an idler beam propagation factor of ∼5.

SESAM mode-locked Yb:GdScO3 laser.

We report on the investigation of continuous-wave (CW) and SEmiconductor Saturable Absorber Mirror (SESAM) mode-locked operation of a Yb:GdScO3 laser. Using a single-transverse-mode, fiber-coupled InGaAs laser diode at 976 nm as a pump source, the Yb:GdScO3 laser delivers 343 mW output power at 1062 nm in the CW regime, which corresponds to a slope efficiency of 52%. Continuous tuning is possible across a wavelength range of 84 nm (1027-1111 nm). Using a commercial SESAM to initiate mode-locking and stabilize soliton-type pulse shaping, the Yb:GdScO3 laser produces pulses as short as 42 fs at 1065.9 nm, with an average output power of 40 mW at 66.89 MHz. To the best of our knowledge, this is the first demonstration of passively mode-locking with Yb:GdScO3 crystal.

Growth, spectroscopy and SESAM mode-locking of a "mixed" Yb:Ca(Gd,Y)AlO4 disordered crystal.

We present the growth, spectroscopy, continuous-wave (CW) and passively mode-locked (ML) operation of a novel "mixed" tetragonal calcium rare-earth aluminate crystal, Yb3+:Ca(Gd,Y)AlO4. The absorption, stimulated-emission, and gain cross-sections are derived for π and σ polarizations. The laser performance of a c-cut Yb:Ca(Gd,Y)AlO4 crystal is studied using a spatially single-mode, 976-nm fiber-coupled laser diode as a pump source. A maximum output power of 347 mW is obtained in the CW regime with a slope efficiency of 48.9%. The emission wavelength is continuously tunable across 90 nm (1010 - 1100 nm) using a quartz-based Lyot filter. With a commercial SEmiconductor Saturable Absorber Mirror to initiate and maintain ML operation, soliton pulses as short as 35 fs are generated at 1059.8 nm with an average output power of 51 mW at ∼65.95 MHz. The average output power can be scaled to 105 mW for slightly longer pulses of 42 fs at 1063.5 nm.

Continuous-wave and SESAM mode-locked operation of a Yb:YSr3(PO4)3 laser.

We report on the continuous-wave (CW) and, for what we believe to be the first time, passively mode-locked (ML) laser operation of an Yb3+-doped YSr3(PO4)3 crystal. Utilizing a 976-nm spatially single-mode, fiber-coupled laser diode as pump source, the Yb:YSr3(PO4)3 laser delivers a maximum CW output power of 333 mW at 1045.8 nm with an optical efficiency of 55.7% and a slope efficiency of 60.9%. Employing a quartz-based Lyot filter, an impressive wavelength tuning range of 97 nm at the zero level was achieved in the CW regime, spanning from 1007 nm to 1104 nm. In the ML regime, incorporating a commercially available semiconductor saturable absorber mirror (SESAM) to initiate and maintain soliton-like pulse shaping, the Yb:YSr3(PO4)3 laser generated pulses as short as 61 fs at 1062.7 nm, with an average output power of 38 mW at a repetition rate of ∼66.7 MHz.

Narrowband, intracavity-pumped, type-II BaGa2GeSe6 optical parametric oscillator.

We present a tunable (6.62-11.34 µm), singly-resonant, cascade optical parametric oscillator with intracavity pumping of BaGa2GeSe6 in the second stage and spectral narrowing realized by a Volume Bragg Grating acting on the signal wave of the first stage which serves as a pump for the second stage. The maximum energy achieved near 8 µm in the narrowband regime is 1.1 mJ at 100 Hz (spectral width: ∼20 cm-1, pulse duration: ∼7 ns). The overall conversion efficiency from 1 to 8 µm for broadband and narrowband operation is 4.0% and 3.1%, respectively, corresponding to quantum efficiencies of 31% and 23%.

Paeoniflorin loaded liposomes modified with glycyrrhetinic acid for liver-targeting: preparation, characterization, and pharmacokinetic study.

OBJECTIVE: To enhance the retention times and therapeutic efficacy of paeoniflorin (PF), a liver-targeted drug delivery system has been developed using glycyrrhetinic acid (GA) as a ligand. SIGNIFICANCE: The development and optimization of GA-modified PF liposomes (GPLs) have shown promising potential for targeted delivery to the liver, opening up new possibilities for liver disease treatment. METHODS: This study aimed to identify the best prescriptions using single-factor experiments and response surface methodology. The formulation morphology was determined using transmission electron microscopy. Tissue distribution was observed through in vivo imaging, and pharmacokinetic studies were conducted. RESULTS: The results indicated that GPLs, prepared using the thin film dispersion method and response surface optimization, exhibited well-dispersed and uniformly sized particles. The in vitro release rate of GPLs was slower compared to PF monomers, suggesting a sustained release effect. The liver-targeting ability of GA resulted in stronger fluorescence signals in the liver for targeted liposomes compared to non-targeted liposomes. Furthermore, pharmacokinetic studies demonstrated that GPLs significantly prolonged the residence time of PF in the bloodstream, thereby contributing to prolonged efficacy. CONCLUSION: These findings suggest that GPLs are more effective than PF monomers in terms of controlling drug release and delivering drugs to specific targets, highlighting the potential of PF as a liver-protective drug.