PoWRKY69-PoVQ11 module positively regulates drought tolerance by accumulating fructose in Paeonia ostii.

Drought is a detrimental environmental factor that restricts plant growth and threatens food security throughout the world. WRKY transcription factors play vital roles in abiotic stress response. However, the roles of IIe subgroup members from WRKY transcription factor family in soluble sugar mediated drought response are largely elusive. In this study, we identified a drought-responsive IIe subgroup WRKY transcription factor, PoWRKY69, from Paeonia ostii. PoWRKY69 functioned as a positive regulator in response to drought stress with nucleus expression and transcriptional activation activity. Silencing of PoWRKY69 increased plants sensitivity to drought stress, whereas conversely, overexpression of PoWRKY69 enhanced drought tolerance in plants. As revealed by yeast one-hybrid, electrophoretic mobility shift assay, and luciferase reporter assays, PoWRKY69 could directly bind to the W-box element of fructose-1,6-bisphosphate aldolase 5 (PoFBA5) promoter, contributing to a cascade regulatory network to activate PoFBA5 expression. Furthermore, virus-induced gene silencing and overexpression assays demonstrated that PoFBA5 functioned positively in response to drought stress by accumulating fructose to alleviate membrane lipid peroxidation and activate antioxidant defense system, these changes resulted in reactive oxygen species scavenging. According to yeast two-hybrid, bimolecular fluorescence complementation, and firefly luciferase complementation imaging assays, valine-glutamine 11 (PoVQ11) physically interacted with PoWRKY69 and led to an enhanced activation of PoWRKY69 on PoFBA5 promoter activity. This study broadens our understanding of WRKY69-VQ11 module regulated fructose accumulation in response to drought stress and provides feasible molecular measures to create novel drought-tolerant germplasm of P. ostii.

Stop codon variant in EFEMP1 is associated with primary open-angle glaucoma due to impaired regulation of aqueous humor outflow.

It is known that the actin cytoskeleton and its associated cellular interactions in the trabecular meshwork (TM) and juxtacanalicular tissues mainly contribute to the formation of resistance to aqueous outflow of the eye. Fibulin-3, encoded by EFEMP1 gene, has a role in extracellular matrix (ECM) modulation, and interacts with enzymatic ECM regulators, but the effects of fibulin-3 on TM cells has not been explored. Here, we report a stop codon variant (c.T1480C, p.X494Q) of EFEMP1 that co-segregates with primary open angle glaucoma (POAG) in a Chinese pedigree. In the human TM cells, overexpression of wild-type fibulin-3 reduced intracellular actin stress fibers formation and the extracellular fibronectin levels by inhibiting Rho/ROCK signaling. TGFß1 up-regulated fibulin-3 protein levels in human TM cells by activating Rho/ROCK signaling. In rat eyes, overexpression of wild-type fibulin-3 decreased the intraocular pressure and the fibronectin expression of TM, however, overexpression of mutant fibulin-3 (c.T1480C, p.X494Q) showed opposite effects in cells and rat eyes. Taken together, the EFEMP1 variant may impair the regulatory capacity of fibulin-3 which has a role for modulating the cell contractile activity and ECM synthesis in TM cells, and in turn may maintain normal resistance of aqueous humor outflow. This study contributes to the understanding of the important role of fibulin-3 in TM pathophysiology and provides a new possible POAG therapeutic approach.

A Rapid Localization Method Based on Super Resolution Magnetic Array Information for Unknown Number Magnetic Sources.

A rapid method that uses super-resolution magnetic array data is proposed to localize an unknown number of magnets in a magnetic array. A magnetic data super-resolution (SR) neural network was developed to improve the resolution of a magnetic sensor array. The approximate 3D positions of multiple targets were then obtained based on the normalized source strength (NSS) and magnetic gradient tensor (MGT) inversion. Finally, refined inversion of the position and magnetic moment was performed using a trust region reflective algorithm (TRR). The effectiveness of the proposed method was examined using experimental field data collected from a magnetic sensor array. The experimental results showed that all the targets were successfully captured in multiple trials with three to five targets with an average positioning error of less than 3 mm and an average time of less than 300 ms.

Effect of the coloring liquid shade and dipping time on the color, transparency, and flexural strength of monolithic zirconia.

STATEMENT OF PROBLEM: The impact of different coloring liquid shades and dipping times on the color, transparency, and flexural strength of monolithic zirconia ceramics is unclear. PURPOSE: The purpose of this in vitro study was to evaluate the effects of different coloring liquid shades (A2, 3M2, and 5M2) and dipping times (no dipping, 30 seconds, 60 seconds, and 90 seconds) on the color difference (ΔE00), relative translucency parameter (ΔRTP00), and 3-point flexural strength (σ) of monolithic zirconia ceramics. MATERIAL AND METHODS: Yttria-stabilized zirconia (3Y-TZP, 3 mol%) was cut into Ø16×1.2-mm plates (n=10) and 25×4×1.2-mm bars (n=15), which were colored using 3 shades of coloring liquid at 4 dipping times. Color coordinates were measured on a gray background by using a digital spectrophotometer with an integrating sphere attachment. The color and translucency differences were evaluated using 50:50% perceptibility (PT00 and TPT00) and acceptability (AT00 and TAT00) thresholds. The 3-point flexural strengths of the bar-shaped specimens were measured using a universal testing machine and analyzed using the Weibull distribution to calculate the Weibull modulus (m) and characteristic fracture strength (σ0). The data were analyzed with the 2-way ANOVA, Kruskal-Wallis, and LSD post hoc tests (α=.05). RESULTS: Both shade and dipping time significantly affected the color and translucency of monolithic zirconia (P<.001). The ΔE00 was above the PT00 for all groups, with only 3M2-90 and A2-60 being below the AT00. The main cause of color differences was the difference in lightness. Only A2 showed ΔRTP00 below the TPT00 (A2-30 (ΔRTP00=0.26), A2-60 (ΔRTP00=0.29), and A2-90 (ΔRTP00=0.46)). All experimental groups showed translucency differences below TAT00. In addition, only the dipping time had a significant effect on the flexural strength of zirconia (P<.001). CONCLUSIONS: The optical properties of monolithic zirconia ceramics were affected by the shade and dipping time of the coloring liquid. The mismatch in lightness was the main reason for the color difference. The dipping time affects the flexural strength of monolithic zirconia, whereas the shade of the coloring liquid did not seem to influence flexural strength.

Two-Orders-of-Magnitude Enhancement of Photoinitiation Activity via a Simple Surface Engineering of Metal Nanoclusters.

Development of high-performance photoinitiator is the key to enhance the printing speed, structure resolution and product quality in 3D laser printing. Here, to improve the printing efficiency of 3D laser nanoprinting, we investigate the underlying photochemistry of gold and silver nanocluster initiators under multiphoton laser excitation. Experimental results and DFT calculations reveal the high cleavage probability of the surface S-C bonds in gold and silver nanoclusters which generate multiple radicals. Based on this understanding, we design several alkyl-thiolated gold nanoclusters and achieve a more than two-orders-of-magnitude enhancement of photoinitiation activity, as well as a significant improvement in printing resolution and fabrication window. Overall, this work for the first time unveils the detailed radical formation pathways of gold and silver nanoclusters under multiphoton activation and substantially improves their photoinitiation sensitivity via surface engineering, which pushes the limit of the printing efficiency of 3D laser lithography.

Research progress in the detection of common foodborne hazardous substances based on functional nucleic acids biosensors.

With the further improvement of food safety requirements, the development of fast, highly sensitive, and portable methods for the determination of foodborne hazardous substances has become a new trend in the food industry. In recent years, biosensors and platforms based on functional nucleic acids, along with a range of signal amplification devices and methods, have been established to enable rapid and sensitive determination of specific substances in samples, opening up a new avenue of analysis and detection. In this paper, functional nucleic acid types including aptamers, deoxyribozymes, and G-quadruplexes which are commonly used in the detection of food source pollutants are introduced. Signal amplification elements include quantum dots, noble metal nanoparticles, magnetic nanoparticles, DNA walkers, and DNA logic gates. Signal amplification technologies including nucleic acid isothermal amplification, hybridization chain reaction, catalytic hairpin assembly, biological barcodes, and microfluidic system are combined with functional nucleic acids sensors and applied to the detection of many foodborne hazardous substances, such as foodborne pathogens, mycotoxins, residual antibiotics, residual pesticides, industrial pollutants, heavy metals, and allergens. Finally, the potential opportunities and broad prospects of functional nucleic acids biosensors in the field of food analysis are discussed.

Tree peony PsMYB44 negatively regulates petal blotch distribution by inhibiting dihydroflavonol-4-reductase gene expression.

BACKGROUND AND AIMS: The tree peony (Paeonia suffruticosa Andr.) has been widely cultivated as a field plant, and petal blotch is one of its important traits, which not only promotes proliferation but also confers high ornamental value. However, the regulatory network controlling blotch formation remains elusive owing to the functional differences and limited conservation of transcriptional regulators in dicots. METHODS: We performed phylogenetic analysis to identify MYB44-like transcription factors in P. suffruticosa blotched cultivar 'High noon' petals. A candidate MYB44-like transcription factor, PsMYB44, was analysed via expression pattern analysis, subcellular localization, target gene identification, gene silencing in P. suffruticosa petals and heterologous overexpression in tobacco. KEY RESULTS: A blotch formation-related MYB44-like transcription factor, PsMYB44, was cloned. The C-terminal of the PsMYB44 amino acid sequence had a complete C2 motif that affects anthocyanin biosynthesis, and PsMYB44 was clustered in the MYB44-like transcriptional repressor branch. PsMYB44 was located in the nucleus, and its spatial and temporal expression patterns were negatively correlated with blotch formation. Furthermore, a yeast one-hybrid assay showed that PsMYB44 could target the promoter of the late anthocyanin biosynthesis-related dihydroflavonol-4-reductase (DFR) gene, and a dual-luciferase assay demonstrated that PsMYB44 could repress PsDFR promoter activity. On the one hand, overexpression of PsMYB44 significantly faded the red colour of tobacco flowers and decreased the anthocyanin content by 42.3 % by downregulating the expression level of the tobacco NtDFR gene. On the other hand, PsMYB44-silenced P. suffruticosa petals had a redder blotch colour, which was attributed to the fact that silencing PsMYB44 redirected metabolic flux to the anthocyanin biosynthesis branch, thereby promoting more anthocyanin accumulation in the petal base. CONCLUSION: These results demonstrated that PsMYB44 negatively regulated the biosynthesis of anthocyanin by directly binding to the PsDFR promoter and subsequently inhibiting blotch formation, which helped to elucidate the molecular regulatory network of anthocyanin-mediated blotch formation in plants.

Synthesis of a Porous [14]Annulene Graphene Nanoribbon and a Porous [30]Annulene Graphene Nanosheet on Metal Surfaces.

The electrical and mechanical properties of graphene-based materials can be tuned by the introduction of nanopores, which are sensitively related to the size, morphology, density, and location of nanopores. The synthesis of low-dimensional graphene nanostructures containing well-defined nonplanar nanopores has been challenging due to the intrinsic steric hindrance. Herein, we report the selective synthesis of one-dimensional (1D) graphene nanoribbons (GNRs) containing periodic nonplanar [14]annulene pores on Ag(111) and two-dimensional (2D) porous graphene nanosheet containing periodic nonplanar [30]annulene pores on Au(111), starting from a same precursor. The formation of distinct products on the two substrates originates from the different thermodynamics and kinetics of coupling reactions. The reaction mechanisms were confirmed by a series of control experiments, and the appropriate thermodynamic and kinetic parameters for optimizing the reaction pathways were proposed. In addition, the combined scanning tunneling spectroscopy (STS) and density functional theory (DFT) calculations revealed the electronic structures of porous graphene structures, demonstrating the impact of nonplanar pores on the π-conjugation of molecules.

Automatic segmentation of the gross target volume in radiotherapy for lung cancer using transresSEUnet 2.5D Network.

OBJECTIVE: This paper intends to propose a method of using TransResSEUnet2.5D network for accurate automatic segmentation of the Gross Target Volume (GTV) in Radiotherapy for lung cancer. METHODS: A total of 11,370 computed tomograms (CT), deriving from 137 cases, of lung cancer patients under radiotherapy developed by radiotherapists were used as the training set; 1642 CT images in 20 cases were used as the validation set, and 1685 CT images in 20 cases were used as the test set. The proposed network was tuned and trained to obtain the best segmentation model and its performance was measured by the Dice Similarity Coefficient (DSC) and with 95% Hausdorff distance (HD95). Lastly, as to demonstrate the accuracy of the automatic segmentation of the network proposed in this study, all possible mirrors of the input images were put into Unet2D, Unet2.5D, Unet3D, ResSEUnet3D, ResSEUnet2.5D, and TransResUnet2.5D, and their respective segmentation performances were compared and assessed. RESULTS: The segmentation results of the test set showed that TransResSEUnet2.5D performed the best in the DSC (84.08 ± 0.04) %, HD95 (8.11 ± 3.43) mm and time (6.50 ± 1.31) s metrics compared to the other three networks. CONCLUSIONS: The TransResSEUnet 2.5D proposed in this study can automatically segment the GTV of radiotherapy for lung cancer patients with more accuracy.

Analysis and Functional Verification of PlPM19L Gene Associated with Drought-Resistance in Paeonia lactiflora Pall.

The herbaceous peony (Paeonia lactiflora Pall.) is widely cultivated as an ornamental, medicinal and edible plant in China. Drought stress can seriously affect the growth of herbaceous peony and reduce its quality. In our previous research, a significantly differentially expressed gene, PM19L, was obtained in herbaceous peony under drought stress based on transcriptome analysis, but little is known about its function. In this study, the first PM19L that was isolated in herbaceous peony was comprised of 910 bp, and was designated as PlPM19L (OP480984). It had a complete open reading frame of 537 bp and encoded a 178-amino acid protein with a molecular weight of 18.95 kDa, which was located in the membrane. When PlPM19L was transferred into tobacco, the transgenic plants had enhanced tolerance to drought stress, potentially due to the increase in the abscisic acid (ABA) content and the reduction in the level of hydrogen peroxide (H2O2). In addition, the enhanced ability to scavenge H2O2 under drought stress led to improvements in the enzyme activity and the potential photosynthetic capacity. These results combined suggest that PlPM19L is a key factor to conferring drought stress tolerance in herbaceous peony and provide a scientific theoretical basis for the following improvement in the drought resistance of herbaceous peony and other plants through genetic engineering technology.

Twelve Chinese herbal preparations for the treatment of depression or depressive symptoms in cancer patients: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Patients with cancer are vulnerable to depression or other depressive conditions. The aim of this paper was to evaluate the efficacy and safety of Chinese herbal medicine (CHM) for the treatment of depression or depressive symptoms in cancer patients. METHODS: CENTRAL, MEDLINE, EMBASE, PsycINFO, CNKI, VIP, SinoMed, and online clinical trial registry websites were searched for relevant RCTs until May 2017. The methodological quality of each included study was assessed with the "risk of bias" tool. Review Manager 5.3.5 was used to analyze the data. RESULTS: We identified 18 RCTs that included data from 1441 participants. Twelve different types of Chinese herbal preparations were investigated by these studies, and they showed a better therapeutic effect in most comparisons when measured in terms of depression rating scale scores, with SMDs (95% CI) of - 2.30 (- 3.54, - 1.05) (CHM versus no treatment), - 0.61 (- 1.03, - 0.18) (CHM versus antidepressants), and - 0.55 (- 1.07, - 0.02) (CHM plus psychological treatments versus psychological treatments), or when measured in terms of treatment response rate, with RRs (95% CI) of 1.65 (1.19, 2.29) (CHM versus no treatment), 1.15 (1.03, 1.28) (CHM versus psychological treatments), 1.32 (1.07, 1.63) (CHM plus antidepressants versus antidepressants), and 1.70 (1.02, 2.85) (CHM plus psychological treatments versus psychological treatments). Compared with antidepressants, these CHMs showed borderline superiority for improving the response rate, with an RR (95% CI) of 1.08 (0.93, 1.26). Subgroup analysis based on psychiatric diagnosis (depression versus depressive symptoms) did not modify the direction of these estimates and neither could it explain the high level of heterogeneity. Patients in the CHM group experienced fewer adverse events of cardiac toxicity (P = 0.02), functional gastrointestinal disorders (P = 0.008), sleep disturbances (P = 0.02), blurred vision (P = 0.02) and fatigue (P = 0.03) than the patients in the no treatment group or the antidepressants group. CONCLUSIONS: According to the investigation of the twelve herbal preparations, the CHM intervention appears to alleviate depressive symptoms in cancer patients, either alone or combined with antidepressants or psychological treatments. However, a high risk of bias and high heterogeneity made the mean estimates uncertain. Well-designed trials with comprehensive and transparent reporting are warranted in the future.

Dysregulated interactions between lamin A and SUN1 induce abnormalities in the nuclear envelope and endoplasmic reticulum in progeric laminopathies.

Hutchinson-Gilford progeria syndrome (HGPS) is a human progeroid disease caused by a point mutation on the LMNA gene. We reported previously that the accumulation of the nuclear envelope protein SUN1 contributes to HGPS nuclear aberrancies. However, the mechanism by which interactions between mutant lamin A (also known as progerin or LAΔ50) and SUN1 produce HGPS cellular phenotypes requires further elucidation. Using light and electron microscopy, this study demonstrated that SUN1 contributes to progerin-elicited structural changes in the nuclear envelope and the endoplasmic reticulum (ER) network. We further identified two domains through which full-length lamin A associates with SUN1, and determined that the farnesylated cysteine within the CaaX motif of lamin A has a stronger affinity for SUN1 than does the lamin A region containing amino acids 607 to 656. Farnesylation of progerin enhanced its interaction with SUN1 and reduced SUN1 mobility, thereby promoting the aberrant recruitment of progerin to the ER membrane during postmitotic assembly of the nuclear envelope, resulting in the accumulation of SUN1 over consecutive cellular divisions. These results indicate that the dysregulated interaction of SUN1 and progerin in the ER during nuclear envelope reformation determines the progression of HGPS.

Aurora kinase inhibitors reveal mechanisms of HURP in nucleation of centrosomal and kinetochore microtubules.

The overexpression of Aurora kinases in multiple tumors makes these kinases appealing targets for the development of anticancer therapies. This study identified two small molecules with a furanopyrimidine core, IBPR001 and IBPR002, that target Aurora kinases and induce a DFG conformation change at the ATP site of Aurora A. Our results demonstrate the high potency of the IBPR compounds in reducing tumorigenesis in a colorectal cancer xenograft model in athymic nude mice. Human hepatoma up-regulated protein (HURP) is a substrate of Aurora kinase A, which plays a crucial role in the stabilization of kinetochore fibers. This study used the IBPR compounds as well as MLN8237, a proven Aurora A inhibitor, as chemical probes to investigate the molecular role of HURP in mitotic spindle formation. These compounds effectively eliminated HURP phosphorylation, thereby revealing the coexistence and continuous cycling of HURP between unphosphorylated and phosphorylated forms that are associated, respectively, with microtubules emanating from centrosomes and kinetochores. Furthermore, these compounds demonstrate a spatial hierarchical preference for HURP in the attachment of microtubules extending from the mother to the daughter centrosome. The finding of inequality in the centrosomal microtubules revealed by these small molecules provides a versatile tool for the discovery of new cell-division molecules for the development of antitumor drugs.

Precision dose prediction for breast cancer patients undergoing IMRT: The Swin-UMamba-Channel Model.

BACKGROUND: Radiation therapy is one of the crucial treatment modalities for cancer. An excellent radiation therapy plan relies heavily on an outstanding dose distribution map, which is traditionally generated through repeated trials and adjustments by experienced physicists. However, this process is both time-consuming and labor-intensive, and it comes with a degree of subjectivity. Now, with the powerful capabilities of deep learning, we are able to predict dose distribution maps more accurately, effectively overcoming these challenges. METHODS: In this study, we propose a novel Swin-UMamba-Channel prediction model specifically designed for predicting the dose distribution of patients with left breast cancer undergoing radiotherapy after total mastectomy. This model integrates anatomical position information of organs and ray angle information, significantly enhancing prediction accuracy. Through iterative training of the generator (Swin-UMamba) and discriminator, the model can generate images that closely match the actual dose, assisting physicists in quickly creating DVH curves and shortening the treatment planning cycle. Our model exhibits excellent performance in terms of prediction accuracy, computational efficiency, and practicality, and its effectiveness has been further verified through comparative experiments with similar networks. RESULTS: The results of the study indicate that our model can accurately predict the clinical dose of breast cancer patients undergoing intensity-modulated radiation therapy (IMRT). The predicted dose range is from 0 to 50 Gy, and compared with actual data, it shows a high accuracy with an average Dice similarity coefficient of 0.86. Specifically, the average dose change rate for the planning target volume ranges from 0.28 % to 1.515 %, while the average dose change rates for the right and left lungs are 2.113 % and 0.508 %, respectively. Notably, due to their small sizes, the heart and spinal cord exhibit relatively higher average dose change rates, reaching 3.208 % and 1.490 %, respectively. In comparison with similar dose studies, our model demonstrates superior performance. Additionally, our model possesses fewer parameters, lower computational complexity, and shorter processing time, further enhancing its practicality and efficiency. These findings provide strong evidence for the accuracy and reliability of our model in predicting doses, offering significant technical support for IMRT in breast cancer patients. CONCLUSION: This study presents a novel Swin-UMamba-Channel dose prediction model, and its results demonstrate its precise prediction of clinical doses for the target area of left breast cancer patients undergoing total mastectomy and IMRT. These remarkable achievements provide valuable reference data for subsequent plan optimization and quality control, paving a new path for the application of deep learning in the field of radiation therapy.

Cynaroside improved depressive-like behavior in CUMS mice by suppressing microglial inflammation and ferroptosis.

Depression is a common mental health disorder, and in recent years, the incidence of various forms of depression has been on the rise. Most medications for depression are highly dependency-inducing and can lead to relapse upon discontinuation. Therefore, novel treatment modalities and therapeutic targets are urgently required. Traditional Chinese medicine (TCM) offers advantages in the treatment of depression owing to its multi-target, multi-dimensional approach that addresses the root cause of depression by regulating organ functions and balancing Yin and Yang, with minimal side effects. Cynaroside (CNS), an extract from the traditional Chinese herb honeysuckle, is a flavonoid compound with antioxidant properties. In this study, network pharmacology identified 44 potential targets of CNS associated with depression and several highly correlated inflammatory signaling pathways. CNS alleviated LPS-induced M1 polarization and the release of inflammatory factors in BV-2 cells. Transcriptomic analysis and validation revealed that CNS reduced inflammatory polarization, lipid peroxidation, and ferroptosis via the IRF1/SLC7A11/GPX4 signaling pathway. In vivo experiments showed that CNS treatment had effects similar to those of fluoxetine (FLX). It effectively ameliorated anxiety-, despair-, and anhedonia-like states in chronic unpredictable mild stress (CUMS)-induced mice and reduced microglial activation in the hippocampus. Thus, we conclude that CNS exerts its therapeutic effect on depression by inhibiting microglial cells from polarizing into the M1 phenotype and reducing inflammation and ferroptosis levels. This study provides further evidence that CNS is a potential antidepressant, offering new avenues for the treatment of depression.

Integrated Optimization of Structure and Control for Fast Steering Mirrors.

This study concerns the problem of integrated optimization of structure and control based on a fast steering mirror, aiming to achieve simultaneous optimization of the mechanical structure and control system. The traditional research and development path of the fast steering mirror involves a lengthy process from the initial design to the final physical manufacture. In the prior process, it was necessary to produce physical prototypes for repeated debugging and iterative optimization to achieve design requirements, but this approach consumes a significant amount of time and cost. To expedite this process and reduce unnecessary experimental costs, this study proposes an integrated optimization of structure and control (IOSC) method. With the use of IOSC, it is possible to achieve simultaneous optimization of structure and control. Specifically, the use of non-dominated sorting genetic algorithm II (NSGA-II) obtains globally optimal controller parameters and mechanical structure parameters under certain performance indices. This achieves an effective balance between the resonance frequency generated by the system and the working bandwidth, providing a high-precision reference for the research and development of fast steering mirrors.

Management of Pseudophakic Malignant Glaucoma Using Modified Nd:YAG Laser Treatment Methodology Through Surgical Preset Iridectomy.

INTRODUCTION: The use of the neodymium:yttrium-aluminum-garnet (Nd:YAG) laser to treat malignant glaucoma (MG) has been described in the literature since the 1980s. However, the technique has been reported to have a short-term effect, with a notable relapse rate. In the present study, we report the efficacy and durability of a modified Nd:YAG laser treatment methodology for treatment of pseudophakic or aphakic MG. METHODS: Patients with chronic angle-closure glaucoma and deemed at high risk of developing post-operative MG received prophylactic peripheral iridectomy during their conventional operation beginning in 2017. When the diagnosis of pseudophakic or aphakic MG was confirmed, a thorough Nd:YAG laser capsulo/zonulo-hyaloido-vitreolysis (CZHV) was performed through iridectomy, along with standardized pre- and post-laser medications. This retrospective case series includes 14 eyes of 11 patients with MG who had surgical preset iridectomy and modified Nd:YAG laser CZHV between 2017 and 2022. Outcome measures included resolution and recurrence of MG and incidence of treatment complications. RESULTS: The mean follow-up was 27.1 ± 15.0 months (range, 12-48). Long-term resolution of MG was obtained in all included eyes at the end of the follow-up. Six eyes (42.9%) achieved long-term resolution with a single Nd:YAG laser intervention. Eight eyes (57.1%) achieved long-term resolution following two to three laser interventions, with two eyes (14.3%) experiencing recurrence. There was no complication during the follow-up. At the final visit, a significant reduction (P = 0.0001) in the mean intraocular pressure (IOP) was observed (13.1 ± 2.8 mmHg) compared to presentation (21.4 ± 6.3 mmHg). CONCLUSION: The modified Nd:YAG laser treatment methodology is a minimally invasive option to manage pseudophakic or aphakic MG with sustained effectiveness. Reduced inflammatory reactions due to prophylactic peripheral iridectomy, rapid diagnosis, and timely treatment initiation have all contributed to the favorable outcomes associated with this modified treatment methodology.

Identification of arnicolide C as a novel chemosensitizer to suppress mTOR/E2F1/FANCD2 axis in non-small cell lung cancer.

BACKGROUND AND PURPOSE: The mammalian target of rapamycin (mTOR) pathway plays critical roles in intrinsic chemoresistance by regulating Fanconi anaemia complementation group D2 (FANCD2) expression. However, the mechanisms by which mTOR regulates FANCD2 expression and related inhibitors are not clearly elucidated. Extracts of Centipeda minima (C. minima) showed promising chemosensitizing effects by inhibiting FANCD2 activity. Here, we have aimed to identify the bioactive chemosensitizer in C. minima extracts and elucidate its underlying mechanism. EXPERIMENTAL APPROACH: The chemosensitizing effects of arnicolide C (ArC), a bioactive compound in C. minima, on non-small cell lung cancer (NSCLC) were investigated using immunoblotting, immunofluorescence, flow cytometry, the comet assay, small interfering RNA (siRNA) transfection and animal models. The online SynergyFinder software was used to determine the synergistic effects of ArC and chemotherapeutic drugs on NSCLC cells. KEY RESULTS: ArC had synergistic cytotoxic effects with DNA cross-linking drugs such as cisplatin and mitomycin C in NSCLC cells. ArC treatment markedly decreased FANCD2 expression in NSCLC cells, thus attenuating cisplatin-induced FANCD2 nuclear foci formation, leading to DNA damage and apoptosis. ArC inhibited the mTOR pathway and attenuated mTOR-mediated expression of E2F1, a critical transcription factor of FANCD2. Co-administration of ArC and cisplatin exerted synergistic anticancer effects in the A549 xenograft mouse model by suppressing mTOR/FANCD2 signalling in tumour tissues. CONCLUSION AND IMPLICATIONS: ArC suppressed DNA cross-linking drug-induced DNA damage response by inhibiting the mTOR/E2F1/FANCD2 signalling axis, serving as a chemosensitizing agent. This provides insight into the anticancer mechanisms of ArC and offers a potential combinatorial anticancer therapeutic strategy.

PoWRKY71 is involved in Paeonia ostii resistance to drought stress by directly regulating light-harvesting chlorophyll a/b-binding 151 gene.

Although the functions of WRKY transcription factors in drought resistance are well known, their regulatory mechanisms in response to drought by stabilising photosynthesis remain unclear. Here, a differentially expressed PoWRKY71 gene that was highly expressed in drought-treated Paeonia ostii leaves was identified through transcriptome analysis. PoWRKY71 positively responded to drought stress with significantly enhanced expression patterns and overexpressing PoWRKY71 in tobacco greatly improved plant tolerance to drought stress, whereas silencing PoWRKY71 in P. ostii resulted in a drought-intolerant phenotype. Furthermore, lower chlorophyll contents, photosynthesis, and inhibited expression of photosynthesis-related light-harvesting chlorophyll a/b-binding 151 (CAB151) gene were found in PoWRKY71-silenced P. ostii. Meanwhile, a homologous system indicated that drought treatment increased PoCAB151 promoter activity. Interactive assays revealed that PoWRKY71 directly bound on the W-box element of PoCAB151 promoter and activated its transcription. In addition, PoCAB151 overexpressing plants demonstrated increased drought tolerance, together with significantly higher chlorophyll contents and photosynthesis, whereas these indices were dramatically lower in PoCAB151-silenced P. ostii. The above results indicated that PoWRKY71 activated the expression of PoCAB151, thus stabilising photosynthesis via regulating chloroplast homeostasis and chlorophyll content in P. ostii under drought stress. This study reveals a novel drought-resistance mechanism in plants and provides a feasible strategy for improving plant drought resistance via stabilising photosynthesis.

Improved accuracy of auto-segmentation of organs at risk in radiotherapy planning for nasopharyngeal carcinoma based on fully convolutional neural network deep learning.

OBJECTIVE: We examined a modified encoder-decoder architecture-based fully convolutional neural network, OrganNet, for simultaneous auto-segmentation of 24 organs at risk (OARs) in the head and neck, followed by validation tests and evaluation of clinical application. MATERIALS AND METHODS: Computed tomography (CT) images from 310 radiotherapy plans were used as the experimental data set, of which 260 and 50 were used as the training and test sets, respectively. An improved U-Net architecture was established by introducing a batch normalization layer, residual squeeze-and-excitation layer, and unique organ-specific loss function for deep learning training. The performance of the trained network model was evaluated by comparing the manual-delineation and the STAPLE contour of 10 physicians from different centers. RESULTS: Our model achieved good segmentation in all 24 OARs in nasopharyngeal cancer radiotherapy plan CT images, with an average Dice similarity coefficient of 83.75%. Specifically, the mean Dice coefficients in large-volume organs (brainstem, spinal cord, left/right parotid glands, left/right temporal lobes, and left/right mandibles) were 84.97% - 95.00%, and in small-volume organs (pituitary, lens, optic nerve, and optic chiasma) were 55.46% - 91.56%. respectively. Using the STAPLE contours as standard contour, the OrganNet achieved comparable or better DICE in organ segmentation then that of the manual-delineation as well. CONCLUSION: The established OrganNet enables simultaneous automatic segmentation of multiple targets on CT images of the head and neck radiotherapy plans, effectively improves the accuracy of U-Net based segmentation for OARs, especially for small-volume organs.