A Bivalent Aptamer-Based DNA Agonist for EGFR Signaling Effectively Alleviates Ulcerative Colitis In Vivo.

While epidermal growth factor (EGF) shows promise in addressing the clinical manifestations of intestinal ulcerative diseases by activating the EGF receptor (EGFR)-mediated cell signaling, its clinical application is hampered by poor protein hydrolytic stability, low thermostability, and difficulty in modification. The development of a novel EGFR agonist for ulcerative colitis remains an urgent need, necessitating innovative solutions to overcome the limitations of current therapies via recombinant EGF protein. Herein, we introduce a novel DNA agonist for EGFR, Dimer-YL, which employs a bivalent aptamer to induce stable receptor dimerization, thereby activating the EGFR signaling and related cell behaviors. Dimer-YL has been demonstrated to recapitulate the EGF-promoted cellular behaviors, including proliferation and migration, as well as repair the damage of intercellular tight junctions. Furthermore, our findings demonstrate the potent therapeutic function of Dimer-YL in alleviating DSS-induced ulcerative colitis in vivo. Together, the present work has revealed Dimer-YL as an innovative DNA molecule for effective EGFR activation, offering promise for the development of EGFR-agonistic agents for therapeutic purposes.

Hydrogen peroxide sulfenylates and inhibits the photorespiratory enzyme PGLP1 to modulate plant thermotolerance.

Climate change is resulting in more frequent and rapidly changing temperatures at both extremes that severely affect the growth and production of plants, particularly crops. Oxidative stress caused by high temperatures is one of the most damaging factors for plants. However, the role of hydrogen peroxide (H2O2) in modulating plant thermotolerance is largely unknown, and the regulation of photorespiration essential for C3 species remains to be fully clarified. Here, we report that heat stress promotes H2O2 accumulation in chloroplasts and that H2O2 stimulates sulfenylation of the chloroplast-localized photorespiratory enzyme 2-phosphoglycolate phosphatase 1 (PGLP1) at cysteine 86, inhibiting its activity and promoting the accumulation of the toxic metabolite 2-phosphoglycolate. We also demonstrate that PGLP1 has a positive function in plant thermotolerance, as PGLP1 antisense lines have greater heat sensitivity and PGLP1-overexpressing plants have higher heat-stress tolerance than the wild type. Together, our results demonstrate that heat-induced H2O2 in chloroplasts sulfenylates and inhibits PGLP1 to modulate plant thermotolerance. Furthermore, targeting CATALASE2 to chloroplasts can largely prevent the heat-induced overaccumulation of H2O2 and the sulfenylation of PGLP1, thus conferring thermotolerance without a plant growth penalty. These findings reveal that heat-induced H2O2 in chloroplasts is important for heat-caused plant damage.

Rice seed vigor detection based on near-infrared hyperspectral imaging and deep transfer learning.

Vigor is one of the important factors that affects rice yield and quality. Rapid and accurate detection of rice seed vigor is of great importance for rice production. In this study, near-infrared hyperspectral imaging technique and transfer learning were combined to detect rice seed vigor. Four varieties of artificial-aged rice seeds (Yongyou12, Yongyou1540, Suxiangjing100, and Longjingyou1212) were studied. Different convolutional neural network (CNN) models were built to detect the vigor of the rice seeds. Two transfer strategies, fine-tuning and MixStyle, were used to transfer knowledge among different rice varieties for vigor detection. The experimental results showed that the convolutional neural network model of Yongyou12 classified the vigor of Yongyou1540, Suxiangjing100, and Longjingyou1212 through MixStyle transfer knowledge, and the accuracy reached 90.00%, 80.33%, and 85.00% in validation sets, respectively, which was better or close to the initial modeling performances of each variety. MixStyle statistics are based on probabilistic mixed instance-level features of cross-source domain training samples. When training instances, new domains can be synthesized, which increases the domain diversity of the source domain, thereby improving the generalization ability of the trained model. This study would help rapid and accurate detection of a large varieties of crop seeds.

Identification of geographical origins of Radix Paeoniae Alba using hyperspectral imaging with deep learning-based fusion approaches.

The Radix Paeoniae Alba (Baishao) is a traditional Chinese medicine (TCM) with numerous clinical and nutritional benefits. Rapid and accurate identification of the geographical origins of Baishao is crucial for planters, traders and consumers. Hyperspectral imaging (HSI) was used in this study to acquire spectral images of Baishao samples from its two sides. Convolutional neural network (CNN) and attention mechanism was used to distinguish the origins of Baishao using spectra extracted from one side. The data-level and feature-level deep fusion models were proposed using information from both sides of the samples. CNN models outperformed the conventional machine learning methods in classifying Baishao origins. The generalized Gradient-weighted Class Activation Mapping (Grad-CAM++) was utilized to visualize and identify important wavelengths that significantly contribute to model performance. The overall results illustrated that HSI combined with deep learning strategies was effective in identifying the geographical origins of Baishao, having good prospects of real-world applications.

Identification and expression profiles of xylogen-like arabinogalactan protein (XYLP) gene family in Phyllostachys edulis in different developmental tissues and under various abiotic stresses.

Xylogen-like arabinogalactan protein (XYLP) is an atypical lipid transport protein. In this study, 23 Phyllostachys edulis XYLPs were identified, and their proteins contain characteristic structures of AGP and nsLTP domain. All PeXYLPs can be divided into four clades, and their genes were unevenly distributed on 11 chromosome scaffolds. Collinear analysis revealed that segmental duplication was the main driver for PeXYLP family expansion. The cis-acting elements presented in the promoter are involved in various regulations of PeXYLPs expression. G.O. annotation revealed that PeXYLPs are mainly interested in lipid transport and synthesis and primarily function at the plasma membrane. Transcriptome analysis revealed that PeXYLPs were spatiotemporally expressed and displayed significant variability during various tissue development. Besides that, some PeXYLPs also respond to multiple phytohormones and abiotic stresses. By semi-quantitative RT-PCR, the response of some PeXYLPs to MeJA was confirmed, and the proteins were shown to localize to the plasma membrane mainly. WGCNA in defined regions of fast-growing bamboo shoots revealed that 5 PeXYLPs in 4 gene co-expression modules showed a positive module-trait relationship with three fast-growing regions. This systematic analysis of the PeXYLP family will provide a foundation for further insight into the functions of individual PeXYLP in a specific tissue or organ development, phytohormone perception, and stress responses in the future.

Contrastive Unfolding Deraining Network.

Due to the fact that the degradation of image quality caused by rain usually affects outdoor vision tasks, image deraining becomes more and more important. Focusing on the single image deraining (SID) task, in this article, we propose a novel Contrastive Unfolding DEraining Network (CUDEN), which combines the traditional iterative algorithm and deep network, exhibiting excellent performance and nice interpretability. CUDEN transforms the challenge of locating rain streaks into discovering rain features and defines the relationship between the image and feature domains in terms of mapping pairs. To obtain the mapping pairs efficiently, we propose a dynamic multidomain translation (DMT) module for decomposing the original mapping into sub-mappings. To enhance the feature extraction capability of networks, we also propose a new serial multireceptive field fusion (SMF) block, which extracts complex and variable rain features with convolution kernels of different receptive fields. Moreover, we are the first to introduce contrastive learning to the SID task and combine it with perceptual loss to propose a new contrastive perceptual loss (CPL), which is quite generalized and greatly helpful in identifying the appropriate gradient descent direction during training. Extensive experiments on synthetic and real-world datasets demonstrate that our proposed CUDEN outperforms the state-of-the-art (SOTA) deraining networks.

Needle insertion forces and fluid injection pressures during targeting of nerves in a soft embalmed cadaver model.

PURPOSE: Forceful needle-nerve contact and high subepineural pressures and are recognised causes of nerve damage. Pressure and force measurements are necessary to inform the mechanisms of nerve injury, build virtual simulator environments and provide operator feedback during simulation training. However, the range of pressures and forces encountered at tissue layers during targeted needle insertion and fluid injection are not known. METHODS: We built a needle that recorded in-line pressure during fluid injection and continuously measured force at the needle tip. Two anaesthetists were randomised to insert a 21 g block needle at 48 nerve sites on both sides of 3 soft embalmed Thiel cadavers. Our objective was to measure pressure and force during the course of targeted nerve injection at epimysium, in perineural tissue, on epineurium and during subepineural injection. At each interface, we infused a 0.5 ml bolus of embalming solution at a rate of 12 ml min-1 and recorded the pressure response. Force was measured continuously in the background throughout the procedure. RESULTS: Pressure was greater at epineurium and within subepineurium than perineural tissue, geometric ratio (95% CI) 4.7 (3.0-7.3) kPa and 3.8 (2.5-5.7) kPa, respectively, both P < 0.0001. Force on nerve contact and on nerve penetration was greater than force in perineural tissue, geometric ratios (95% CI) 3.0 (1.9-4.7) N and 3.6 (2.2-7.5) N, respectively, both P < 0.0001. On nerve contact, 1 in 6 insertions were ≥ 5 N CONCLUSIONS: Despite valid infusion pressures, anaesthetists exerted excessive force on nerves.

Interstitial Cystitis: Cost, treatment and co-morbidities in an employed population.

INTRODUCTION: Recent literature indicates that interstitial cystitis (IC) may affect 20% of women and a smaller proportion of men, although many individuals with IC may be misdiagnosed or remain undiagnosed. Factors that can contribute to the cost of IC include medical and drug utilisation related to treatment and diagnosis of IC and associated conditions (e.g. depression), as well as employee work loss. This study assesses the direct medical cost and indirect cost of work loss for IC patients in the first year after diagnosis, and evaluates IC treatment patterns and prevalence of co-morbidities. METHODS: Data for patients under the age of 65 years with at least one diagnosis of IC (n = 749) were drawn from a de-identified, administrative database of approximately 2 million beneficiaries that included medical, drug and disability claims for 1999-2002. A 2 : 1 matched control sample of patients without an IC diagnosis (non-IC sample) was randomly selected based on patient characteristics. Indirect costs were calculated from a subgroup of 152 IC patients (plus their matched controls) who had disability information available. Costs incurred in the first year after IC diagnosis and co-morbidities were compared between IC patients and the non-IC sample, with the difference in costs defined as 'excess costs' of IC patients. Treatment patterns were profiled in the 2 months following initial diagnosis of IC. Descriptive statistics are presented. A multivariate two-part model was applied to estimate the IC direct medical cost, indirect cost and total cost to adjust for observed patient demographics and co-morbidities. Statistical significance was evaluated by the bootstrap method. RESULTS: The average IC patient had 130% higher direct costs (p < 0.05) and the average IC employee patient had 84% higher indirect costs than the average non-IC control individual. IC patients also had a higher diagnostic prevalence of prostatitis (relative risk [RR] = 40.0), endometriosis (RR = 7.4), vulvodynia (RR = 6.9), chronic pelvic pain (RR = 5.8) and urinary tract infections (RR = 5.1) [all p < 0.05]. IC patients were also more likely to report depression (RR = 2.8) and anxiety (RR = 4.5 ) than non-IC controls (all p < 0.05). Seventeen percent of IC patients received pentosan polysulfate therapy, the only US FDA-approved oral drug therapy indicated for treating IC, within the first 2 months after diagnosis. Of these patients, 69% received at least one 'other' drug from the non-approved oral medications studied. Approximately one-third of IC patients received only 'other' drug therapies, and almost half of IC patients received no drug treatment within the first 2 months after the initial diagnosis. CONCLUSIONS: IC is a costly disease associated with co-morbidities. Following diagnosis, patients with IC are commonly untreated or treated with non-approved drug therapies. It is possible that more accurate diagnosis and earlier and more appropriate treatment of IC would lead to better management (or even prevention) of co-morbidities and reduce healthcare costs, and this should be investigated in future studies.