The Gß-like protein Bcgbl1 regulates development and pathogenicity of the gray mold Botrytis cinerea via modulating two MAP kinase signaling pathways.

The fungal Gß-like protein has been reported to be involved in a variety of biological processes, such as mycelial growth, differentiation, conidiation, stress responses and infection. However, molecular mechanisms of the Gß-like protein in regulating fungal development and pathogenicity are largely unknown. Here, we show that the Gß-like protein gene Bcgbl1 in the gray mold fungus Botrytis cinerea plays a pivotal role in development and pathogenicity by regulating the mitogen-activated protein (MAP) kinases signaling pathways. The Bcgbl1 deletion mutants were defective in mycelial growth, sclerotial formation, conidiation, macroconidial morphogenesis, plant adhesion, and formation of infection cushions and appressorium-like structures, resulting in a complete loss of pathogenicity. Bcgbl1 interacted with BcSte50, the adapter protein of the cascade of MAP kinase (MAPK). Bcgbl1 mutants had reduced phosphorylation levels of two MAPKs, namely Bmp1 and Bmp3, thereby reducing infection. However, deletion of Bcgbl1 did not affect the intracellular cAMP level, and exogenous cAMP could not restore the defects. Moreover, Bcgbl1 mutants exhibited defects in cell wall integrity and oxidative stress tolerance. Transcriptional profiling revealed that Bcgbl1 plays a global role in regulation of gene expression upon hydrophobic surface induction. We further uncovered that three target genes encoding the hydrophobic surface binding proteins (HsbAs) contributed to the adhesion and virulence of B. cinerea. Overall, these findings suggest that Bcgbl1 had multiple functions and provided new insights for deciphering the Bcgbl1-mediated network for regulating development and pathogenicity of B. cinerea.

High-Precision and Real-Time Measurement of Water Isotope Ratios Based on a Mid-Infrared Optical Sensor.

A compact spectrometer based on a mid-infrared optical sensor has been developed for high-precision and real-time measurement of water isotope ratios. The instrument uses laser absorption spectroscopy and applies the weighted Kalman filtering method to determine water isotope ratios with high precision and fast time response. The precision of the measurements is 0.41‰ for δ18O and 0.29‰ for δ17O with a 1 s time. This is much faster than the standard running average technique, which takes over 90 s to achieve the same level of precision. The successful development of this compact mid-infrared optical sensor opens up new possibilities for its future applications in atmospheric and breath gas research.

Construction of an ER stress-related prognostic signature for predicting prognosis and screening the effective anti-tumor drug in osteosarcoma.

BACKGROUND: Osteosarcoma is the most common malignant primary bone tumor in infants and adolescents. The lack of understanding of the molecular mechanisms underlying osteosarcoma progression and metastasis has contributed to a plateau in the development of current therapies. Endoplasmic reticulum (ER) stress has emerged as a significant contributor to the malignant progression of tumors, but its potential regulatory mechanisms in osteosarcoma progression remain unknown. METHODS: In this study, we collected RNA sequencing and clinical data of osteosarcoma from The TCGA, GSE21257, and GSE33382 cohorts. Differentially expressed analysis and the least absolute shrinkage and selection operator regression analysis were conducted to identify prognostic genes and construct an ER stress-related prognostic signature (ERSRPS). Survival analysis and time dependent ROC analysis were performed to evaluate the predictive performance of the constructed prognostic signature. The "ESTIMATE" package and ssGSEA algorithm were utilized to evaluate the differences in immune cells infiltration between the groups. Cell-based assays, including CCK-8, colony formation, and transwell assays and co-culture system were performed to assess the effects of the target gene and small molecular drug in osteosarcoma. Animal models were employed to assess the anti-osteosarcoma effects of small molecular drug. RESULTS: Five genes (BLC2, MAGEA3, MAP3K5, STC2, TXNDC12) were identified to construct an ERSRPS. The ER stress-related gene Stanniocalcin 2 (STC2) was identified as a risk gene in this signature. Additionally, STC2 knockdown significantly inhibited osteosarcoma cell proliferation, migration, and invasion. Furthermore, the ER stress-related gene STC2 was found to downregulate the expression of MHC-I molecules in osteosarcoma cells, and mediate immune responses through influencing the infiltration and modulating the function of CD8+ T cells. Patients categorized by risk scores showed distinct immune status, and immunotherapy response. ISOX was subsequently identified and validated as an effective anti-osteosarcoma drug through a combination of CMap database screening and in vitro and in vivo experiments. CONCLUSION: The ERSRPS may guide personalized treatment decisions for osteosarcoma, and ISOX holds promise for repurposing in osteosarcoma treatment.

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%.

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.

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.

In-band pumped Kerr-lens mode-locked Tm,Ho-codoped calcium aluminate laser.

We report on a Kerr-lens mode-locked Tm,Ho-codoped calcium aluminate laser with in-band pumping of the Tm ions by a spatially single-mode 1678 nm Raman fiber laser. The structurally disordered CaGdAlO4 host crystal is also codoped also with the passive Lu ion for additional inhomogeneous line broadening. The Tm,Ho,Lu:CaGdAlO4 laser generates soliton pulses as short as 79 fs at a central wavelength of 2073.6 nm via soft-aperture Kerr-lens mode-locking. The corresponding average output power amounts to 91 mW at a pulse repetition rate of ∼86 MHz. The average output power can be scaled to 842 mW at the expense of slightly longer pulses of 155 fs at 2045.9 nm, which corresponds to a peak power of ∼58 kW. To the best of our knowledge, this represents the first demonstration of an in-band pumped Kerr-lens mode-locked Tm,Ho solid-state laser at ∼2 µm.

Growth, spectroscopy and laser operation of Tm,Ho:GdScO3 perovskite crystal.

We report on the growth, polarized spectroscopy and first laser operation of an orthorhombic (space group Pnma) Tm3+,Ho3+-codoped gadolinium orthoscandate (GdScO3) perovskite-type crystal. A single crystal of 3.76 at.% Tm, 0.35 at.% Ho:GdScO3 was grown by the Czochralski method. Its polarized absorption and fluorescence properties were studied revealing a broadband emission around 2 µm. The parameters of the Tm3+ ↔ Ho3+ energy transfer was quantified, P28 = 1.30 × 10-22 cm3µs-1, and P71 = 0.99 × 10-23 cm3µs-1, and the thermal equilibrium lifetime was measured to be 3.5 ms. The crystal-field splitting of Tm3+ and Ho3+ multiplets in Cs symmetry sites of the perovskite structure was determined by low-temperature spectroscopy and the mechanism of spectral line broadening is discussed. The continuous-wave Tm,Ho:GdScO3 laser generated 1.16 W at ∼2.1 µm with a slope efficiency of 50.5%, a laser threshold of 184 mW, a linear laser polarization (E || c) and a spatially single-mode output. The Tm,Ho:GdScO3 crystal is promising for broadly tunable and femtosecond mode-locked lasers emitting above 2 µm.

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.

Pressure sensing with two-color laser absorption spectroscopy for combustion diagnostics.

Pressure is an important parameter in assessing combustion performance that is typically measured using contact sensors. However, contact sensors usually disturb combustion flows and suffer from the temperature tolerance limit of sensor materials. In this Letter, an innovative noncontact two-color pressure sensing method based on tunable diode laser absorption spectroscopy (TDLAS) is proposed. This makes it possible to measure pressure at high temperature environments for combustion diagnostics. The proposed method uses the linear combination of the collision-broadened linewidths of two H2O absorption lines near 1343 and 1392 nm to measure the pressure. The feasibility and performance of such method have been demonstrated by measuring pressures from 1 to 5 bars at temperatures up to 1300 K with a laser wavelength scanning rate of 20 kHz. Measurement errors were found to be within 3%. Compared to previously reported TDLAS pressure sensors, this method is free from the influence of concentration and can also be combined with the existing two-color TDLAS thermometry to realize a fast, on line, and multi-parameter measurement in combustion diagnostics.

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.

Characterization and quality evaluation of QiXueShuFu Decoction based on fingerprint and ultra-performance liquid chromatography-quadrupole-orbitrap mass spectrometry.

QiXueShuFu Decoction (QXSFD) modified from the Bazhen Decoction which was originally from the classic Ming Dynasty is a traditional folk formula that boosts the body's immune system. However, its ambiguous chemical components limited its quality control evaluation. In this study, ultra-performance liquid chromatography (UPLC) fingerprint combined with multivariate analysis was used to evaluate the quality of 15 batches of QXSFD, and UPLC quadrupole-orbitrap mass spectrometry was used to further examine the chemical components in QXSFD, after which representative compounds from each disassembled prescription were selected for comparison. Fifteen batches of samples had 33 common peaks in which 11 differential components could be used as a reference for subsequent quality control. One hundred forty-three components were identified from QXSFD. Saponins were mainly derived from the monarch, terpenes from the minister, and polysaccharides and glycosides from the assistant. In addition, quantitative assay revealed that the content of ferulic acid, chlorogenic acid, 2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucoside and 3,6'-disinapoyl sucrose in the whole prescription were higher than the contents of each disassembled prescription. This is the first comprehensive quality report on the chemical components of QXSFD, which is important for pharmacodynamic material basis and quality control.

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.

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.

Prevention of Dialysis Catheter Malfunction with Urokinase and Heparin: A Randomized, Controlled Trial.

Objective: To evaluate the effectiveness of urokinase and heparin in preventing catheter infection and dysfunction in permanent hemodialysis tunneled cuffed catheters. Methods: We randomized 153 cases of maintenance hemodialysis patients with newly implanted permanent hemodialysis tunneled cannula catheters from November 2018 to November 2021 for this single-center prospective randomized controlled trial The eligible patients were given one of two treatment plans: Patients in the control group (73 patients) were given heparin (6260 U/mL)three times a week after hemodialysis. The intervention group (80 cases) was administered urokinase(25000 U/mL) on the basis of heparin. After six months of maintenance hemodialysis with the above sealing protocols, the primary result was the frequency of catheter malfunction, and the secondary outcome was the frequency of catheter-associated infection. Results: In the final analysis of 153 patients, catheter malfunctions occurred in 29 of the 80 patients assigned to heparin alone, with an incidence of 36.3%, and 16 of the 73 subjects assigned to urokinase combined with heparin, with a rate of 21.9%. This represents an almost 2-fold increase in the risk of catheter malfunction among patients treated with heparin alone as compared to those treated with urokinase once weekly (hazard ratio, 1.85; 13 patients (16.3%) allocated to heparin alone experienced catheter-related bacteremia, compared to 4 patients (5.5%) assigned to urokinase (hazard ratio, 2.79; 95%CI, 1.08 to 7.22; P = .03). Baseline levels, and adverse events, including bleeding incidents, did not statistically differ between the two groups. Conclusion: Urokinase can be used as a secondary prevention drug for long-term catheter malfunction and infection based on its cheapness, efficacy, and safety, which can effectively save medical costs, and its sealing protocol is simple and suitable for promotion.

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.

Exploring the Mycovirus Sclerotinia sclerotiorum Hypovirulence-Associated DNA Virus 1 as a Biocontrol Agent of White Mold Caused by Sclerotinia sclerotiorum.

Sclerotinia sclerotiorum is a necrotrophic fungal pathogen causing white mold on many important economic crops. Recently, some mycoviruses such as S. sclerotiorum hypovirulence-associated DNA virus 1 (SsHADV-1) converted S. sclerotiorum into a beneficial symbiont that helps plants manage pathogens and other stresses. To explore the potential use of SsHADV-1 as a biocontrol agent in the United States and to test the efficacy of SsHADV-1-infected United States isolates in managing white mold and other crop diseases, SsHADV-1 was transferred from the Chinese strain DT-8 to United States isolates of S. sclerotiorum. SsHADV-1 is readily transmitted horizontally among United States isolates of S. sclerotiorum and consistently conferred hypovirulence to its host strains. Biopriming of dry bean seeds with hypovirulent S. sclerotiorum strains enhanced resistance to white mold, gray mold, and Rhizoctonia root rot. To investigate the underlying mechanisms, endophytic growth of hypovirulent S. sclerotiorum in dry beans was confirmed using PCR, and the expression of 12 plant defense-related genes were monitored before and after infection. The results indicated that the endophytic growth of SsHADV-1-infected strains in plants stimulated the expression of plant immunity pathway genes that assisted a rapid response from the plant to fungal infection. Finally, application of the seed biopriming technology with SsHADV-1-infected hypervirulent strain has promise for the biological control of several diseases of wheat, pea, and sunflower.

The impact of digital economy on carbon total factor productivity: A spatial analysis of major urban agglomerations in China.

Amid global climate imperatives and intensified economic competition, pivoting from China's conventional growth paradigms to innovative economic catalysts emerges as pivotal for its transformative agenda. Drawing on panel data from 141 principal urban conglomerates spanning 2011-2021, this investigation delves into the intricate nexus between the digital economy and carbon total factor productivity. Our empirical analysis unveils a U-shaped trajectory characterizing the digital economy - carbon total factor productivity interplay, accompanied by a congruent spatial spillover dynamic. While digital economy fortifies environmental governance mechanisms through amplified data and media channels, such regulatory frameworks, albeit efficacious in emission abatement, may inadvertently impede economic vitality, thus attenuating carbon total factor productivity. Progressing from digital economy's foundational phase to its comprehensive deployment, its reverberations on capital productivity manifest in a U-shaped curve, invigorating local carbon total factor productivity while potentially undermining adjacent regions. This digital economy - carbon total factor productivity interrelation is accentuated in advanced, non-resource-reliant metropolises with subdued innovation propensities. This discourse proffers nuanced policy implications for sculpting digital economy trajectories and bolstering carbon total factor productivity in a sustainable context.

Designing a sustainable reverse logistics network for used cell phones based on offline and online trading systems.

Unsustainable production and consumption are driving a significant increase in global electronic waste, posing substantial environmental and human health risks. Even in more developed nations, there is the challenge of low collection rates. In response, we integrate offline and online trading systems and design a material efficiency strategy for used cell phones. We propose a new multi-objective optimization framework to maximize profit, carbon emissions reduction, and circularity in the process of recycling and treatment. Considering multi-period, multi-product, multi-echelon features, as well as price sensitive demand, incentives, and qualities, we established a new multi-objective mixed-integer nonlinear programming optimization model. An enhanced, Fast, Non-Dominated Solution Sorting Genetic Algorithm (ASDNSGA-II) is developed for the solution. We used operational data from a leading Chinese Internet platform to validate the proposed optimization framework. The results demonstrate that the reverse logistics network designed achieves a win-win situation regarding profit and carbon emission reduction. This significantly boosts confidence and motivation for engaging in recycling efforts. Online recycling shows robust profitability and carbon reduction capabilities. An effective coordination mechanism for pricing in both online and offline channels should be established, retaining offline methods while gradually transitioning towards online methods. To increase the collection rate, it is essential to jointly implement a transitional strategy, including recycling incentives and subsidy policies. Additionally, elevating customer environmental awareness should be viewed as a long-term strategy, mitigating the cost of increasing collection rates during the market maturity stage (high collection rates).

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.