Genome-wide characterization and functional analysis of the melon TGA gene family in disease resistance through ectopic overexpression in Arabidopsis thaliana.

TGA-binding (TGA) transcription factors, characterized by the basic region/leucine zipper motif (bZIP), have been recognized as pivotal regulators in plant growth, development, and stress responses through their binding to the as-1 element. In this study, the TGA gene families in melon, watermelon, cucumber, pumpkin, and zucchini were comprehensively characterized, encompassing analyses of gene/protein structures, phylogenetic relationships, gene duplication events, and cis-acting elements in gene promoters. Upon transient expression in Nicotiana benthamiana, the melon CmTGAs, with typical bZIP and DOG1 domains, were observed to localize within the nucleus. Biochemical investigation revealed specific interactions between CmTGA2/3/5/8/9 and CmNPR3 or CmNPR4. The CmTGA genes exhibited differential expression patterns in melon plants in response to different hormones like salicylic acid, methyl jasmonate, and ethylene, as well as a fungal pathogen, Stagonosporopsis cucurbitacearum that causes gummy stem blight in melon. The overexpression of CmTGA3, CmTGA8, and CmTGA9 in Arabidopsis plants resulted in the upregulation of AtPR1 and AtPR5 expression, thereby imparting enhanced resistance to Pseudomonas syringae pv. Tomato DC3000. In contrast, the overexpression of CmTGA7 or CmTGA9 resulted in a compromised resistance to Botrytis cinerea, coinciding with a concomitant reduction in the expression levels of AtPDF1.2 and AtMYC2 following infection with B. cinerea. These findings shed light on the important roles of specific CmTGA genes in plant immunity, suggesting that genetic manipulation of these genes could be a promising avenue for enhancing plant immune responses.

Multiscale approach to the characterization of the interfacial properties of micellar casein and whey protein blends and their effects on recombined dairy creams.

In this study, whipped cream with blends of micellar casein (MCN) and whey protein (WPI) in different ratios were prepared to investigate the role of protein interfacial behavior in determining foam properties at multiple scales, using theoretical modeling, and microscopic and macroscopic analysis. Fluid force microscopy has been used for the first time as a more realistic and direct means of analyzing interfaces properties in multiphase systems. The adsorption kinetics showed that the interfacial permeability constant of WPI (4.24 × 10-4 s-1) was significantly higher than that of the MCN (2.97 × 10-4 s-1), and the WPI interfacial layer had a higher modulus of elasticity (71.38 mN/m) than that of the MCN (47.89 mN/m). This model was validated via the mechanical analysis of the fat globules in real emulsions. The WPI-stabilized fat globule was found to have a higher Young's modulus (219.67 Pa), which contributes to the integrity of its fat globule morphology. As the ratio of MCN was increased in the sample, however, both the interfacial modulus and Young's modulus decreased. Moreover, the rate of partial coalescence was found to increase, a phenomenon that decreased the stability of the emulsion and increased the rate of aeration. The mechanical analysis also revealed a higher level of adhesion between MCN-stabilized fat globule (25.16 nN), which increased fat globule aggregation and emulsion viscosity, while improving thixotropic recovery. The synergistic effect of the blended MCN and WPI provided the highest overrun, at 194.53 %. These studies elucidate the role of the interfacial behavior of proteins in determining the quality of whipped cream and provide ideas for the application of proteins in multiphase systems.

Role of Plastic Surgery in the Treatment of Titanium Mesh Exposure Following Cranioplasty.

BACKGROUND: Titanium mesh cranioplasty is the most common strategy for the repair of skull defects. However, as the frequency of cranioplasty increases, the incidence of titanium mesh exposure following cranioplasty increases as well. This study aimed to investigate the methods and outcomes of plastic surgery in the management of titanium mesh exposure following cranioplasty. METHODS: Patients with titanium mesh exposure following cranioplasty were retrospectively selected from January 2016 to August 2021. Titanium mesh exposure was corrected with reconstructive plastic surgery, including skin grafting, expander insertion, partial removal of the exposed mesh, replacement of the mesh, or flap transplantation. RESULTS: This study included 21 patients with titanium mesh exposure with surgical site infection and a variant of scalp deformity. The age of the patients ranged from 18 to 74 years, with the mean age being 54 years. All patients underwent reconstructive plastic surgery and exhibited complete wound healing. The follow-up period ranged from 17 to 90 months. One patient experienced titanium mesh re-exposure and subsequently underwent an additional procedure for the partial removal of the exposed mesh. No serious complications were observed postoperatively. CONCLUSION: Reconstructive plastic surgery can facilitate wound healing at the titanium mesh exposure site following cranioplasty. However, an individualized treatment strategy is required for each patient, and complications should be managed by adopting standard measures.

Graphene-enhanced lateral photovoltaic effect observed in the Ag nanoparticle-covered graphene/n-type silicon.

Graphene is a kind of two-dimensional material with a single-layer carbon structure and has been investigated in many high-performance photodetectors. The lateral photovoltaic effect (LPE) is widely used in the position-sensitive detectors (PSDs) owing to its linear response of photovoltage to the light position. In this Letter, a type of graphene-enhanced LPE is observed in the Ag nanoparticle-covered graphene/n-type Si. The LPE sensitivity can reach 97.3 mV/mm, much higher than the sensitivity of 1.3 mV/mm in the control sample of Ag/Si and 5.2 mV/mm of graphene/Si. Based on the photocarriers' diffusion mechanism, tailoring a photocarrier transfer at the interface of a heterojunction plays a key role for the enhancement. These findings exhibit great application potential of graphene in the field of PSDs and offer an effective method for the optimization of LPE devices.

Emerging therapies for treatment of agitation, psychosis, or apathy in Alzheimer's disease.

INTRODUCTION: Agitation, psychosis, and apathy are prevalent and highly distressing neuropsychiatric symptoms (NPS) of Alzheimer's disease (AD) that have been linked to numerous negative outcomes, including increased mortality, worsened cognitive decline, and caregiver burden. Current treatments for AD-associated agitation, namely atypical antipsychotics, provide some benefits but may increase the risk of serious adverse events and death. Meanwhile, no pharmacotherapies have been approved by regulatory agencies for the treatment of psychosis or apathy in AD. Over the past decade, many new and repurposed drugs have emerged as potential therapeutic options for managing these challenging NPS. AREAS COVERED: This review aims to provide a comprehensive summary of pharmacotherapies that have recently been investigated in phase 2 and 3 clinical trials for the treatment of agitation, psychosis, or apathy in AD. EXPERT OPINION: Novel atypical antipsychotics, serotonergic antidepressants, cannabinoids, and dextromethorphan combination drugs have shown promising results for alleviating agitation. Pimavanserin appears to be the most effective emerging therapy for psychosis while methylphenidate has demonstrated good efficacy for apathy. Further research on biomarkers of NPS severity and treatment response, as well as continued improvements in methodological approaches are needed to advance the field.

A Study on the Growth and Physiological Toxicity Effects of the Combined Exposure of Microplastics and Cadmium on the Vicia faba L. Seedlings.

To investigate the toxicological effects of polystyrene microplastics (PS-MPs), cadmium (Cd), and their combined contamination on the growth and physiological responses of V. faba seedlings, this experiment employed a hydroponic method. The Hoagland nutrient solution served as the control, changes in root growth, physiological and biochemical indicators of V. faba seedlings under different concentrations of PS-MPs (10, 100 mg/L) alone and combined with 0.5 mg/L Cd. The results demonstrated that the root biomass, root vitality, generation rate of superoxide radicals (O2·-), malondialdehyde (MDA) content, and superoxide dismutase (SOD) activity increased with increasing concentration under the influence of PS-MPs alone, while the soluble sugar content and peroxidase (POD) activity decreased. In the combined treatment with Cd, the trends of these indicators are generally similar to the PS-MPs alone treatment group. However, root vitality and SOD activity showed an inverse relationship with the concentration of PS-MPs. Furthermore, laser confocal and electron microscopy scanning revealed that the green fluorescent polystyrene microspheres entered the root tips of the V. faba and underwent agglomeration in the treatment group with a low concentration of PS-MPs alone and a high concentration of composite PS-MPs with Cd.

Bilateral gene therapy in children with autosomal recessive deafness 9: single-arm trial results.

Gene therapy is a promising approach for hereditary deafness. We recently showed that unilateral AAV1-hOTOF gene therapy with dual adeno-associated virus (AAV) serotype 1 carrying human OTOF transgene is safe and associated with functional improvements in patients with autosomal recessive deafness 9 (DFNB9). The protocol was subsequently amended and approved to allow bilateral gene therapy administration. Here we report an interim analysis of the single-arm trial investigating the safety and efficacy of binaural therapy in five pediatric patients with DFNB9. The primary endpoint was dose-limiting toxicity at 6 weeks, and the secondary endpoint included safety (adverse events) and efficacy (auditory function and speech perception). No dose-limiting toxicity or serious adverse event occurred. A total of 36 adverse events occurred. The most common adverse events were increased lymphocyte counts (6 out of 36) and increased cholesterol levels (6 out of 36). All patients had bilateral hearing restoration. The average auditory brainstem response threshold in the right (left) ear was >95 dB (>95 dB) in all patients at baseline, and the average auditory brainstem response threshold in the right (left) ear was restored to 58 dB (58 dB) in patient 1, 75 dB (85 dB) in patient 2, 55 dB (50 dB) in patient 3 at 26 weeks, and 75 dB (78 dB) in patient 4 and 63 dB (63 dB) in patient 5 at 13 weeks. The speech perception and the capability of sound source localization were restored in all five patients. These results provide preliminary insights on the safety and efficacy of binaural AAV gene therapy for hereditary deafness. The trial is ongoing with longer follow-up to confirm the safety and efficacy findings. Chinese Clinical Trial Registry registration: ChiCTR2200063181 .

Clonal hematopoiesis driven by mutated DNMT3A promotes inflammatory bone loss.

Clonal hematopoiesis of indeterminate potential (CHIP) arises from aging-associated acquired mutations in hematopoietic progenitors, which display clonal expansion and produce phenotypically altered leukocytes. We associated CHIP-DNMT3A mutations with a higher prevalence of periodontitis and gingival inflammation among 4,946 community-dwelling adults. To model DNMT3A-driven CHIP, we used mice with the heterozygous loss-of-function mutation R878H, equivalent to the human hotspot mutation R882H. Partial transplantation with Dnmt3aR878H/+ bone marrow (BM) cells resulted in clonal expansion of mutant cells into both myeloid and lymphoid lineages and an elevated abundance of osteoclast precursors in the BM and osteoclastogenic macrophages in the periphery. DNMT3A-driven clonal hematopoiesis in recipient mice promoted naturally occurring periodontitis and aggravated experimentally induced periodontitis and arthritis, associated with enhanced osteoclastogenesis, IL-17-dependent inflammation and neutrophil responses, and impaired regulatory T cell immunosuppressive activity. DNMT3A-driven clonal hematopoiesis and, subsequently, periodontitis were suppressed by rapamycin treatment. DNMT3A-driven CHIP represents a treatable state of maladaptive hematopoiesis promoting inflammatory bone loss.

Novel artificial tricalcium phosphate and magnesium composite graft facilitates angiogenesis in bone healing.

BACKGROUND: Bone grafting is the standard treatment for critical bone defects, but autologous grafts have limitations like donor site morbidity and limited availability, while commercial artificial grafts may have poor integration with surrounding bone tissue, leading to delayed healing. Magnesium deficiency negatively impacts angiogenesis and bone repair. Therefore, incorporating magnesium into a synthetic biomaterial could provide an excellent bone substitute. This study aims to evaluate the morphological, mechanical, and biological properties of a calcium phosphate cement (CPC) sponge composed of tetracalcium phosphate (TTCP) and monocalcium phosphate monohydrate (MCPM), which could serve as an excellent bone substitute by incorporating magnesium. METHODS: This study aims to develop biomedical materials composed mainly of TTCP and MCPM powder, magnesium powder, and collagen. The materials were prepared using a wet-stirred mill and freeze-dryer methods. The particle size, composition, and microstructure of the materials were investigated. Finally, the biological properties of these materials, including 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay for biocompatibility, effects on bone cell differentiation by alkaline phosphatase (ALP) activity assay and tartrate-resistant acid phosphatase (TRAP) activity assay, and endothelial cell tube formation assay for angiogenesis, were evaluated as well. RESULTS: The data showed that the sub-micron CPC powder, composed of TTCP/MCPM in a 3.5:1 ratio, had a setting time shorter than 15 minutes and a compressive strength of 4.39±0.96 MPa. This reveals that the sub-micron CPC powder had an adequate setting time and mechanical strength. We found that the sub-micron CPC sponge containing magnesium had better biocompatibility, including increased proliferation and osteogenic induction effects without cytotoxicity. The CPC sponge containing magnesium also promoted angiogenesis. CONCLUSION: In summary, we introduced a novel CPC sponge, which had a similar property to human bone promoted the biological functions of bone cells, and could serve as a promising material used in bone regeneration for critical bone defects.

Investigating the Mechanism of Microwave-Assisted Enzymolysis Synergized with Magnetic Bead Adsorption for Reducing Ovalbumin Allergenicity through Biomass Spectrometry Analysis.

This study found that, after microwave treatment at 560 W for 30 s, alkaline protease enzymolysis significantly reduced the allergenicity of ovalbumin (OVA). Furthermore, specific adsorption of allergenic anti-enzyme hydrolyzed peptides in the enzymatic products by immunoglobulin G (IgG) bound to magnetic bead further decreased the allergenicity of OVA. The results indicated that microwave treatment disrupts the structure of OVA, increasing the accessibility of OVA to the alkaline protease. A comparison between 17 IgG-binding epitopes identified through high-performance liquid chromatography-higher energy collisional dissociation-tandem mass spectrometry and previously reported immunoglobulin E (IgE)-binding epitopes revealed a complete overlap in binding epitopes at amino acids (AA)125-135, AA151-158, AA357-366, and AA373-381. Additionally, partial overlap was observed at positions AA41-59, AA243-252, and AA320-340. Consequently, these binding epitopes were likely pivotal in eliciting the allergic reaction to OVA, warranting specific attention in future studies. In conclusion, microwave-assisted enzymolysis synergized with magnetic bead adsorption provides an effective method to reduce the allergenicity of OVA.

Multifunctional lipid droplet probes for observing the polarity change of ferroptosis, inflammation, fatty liver and evaluating the efficacy of drugs.

BACKGROUND: Lipid droplets (LDs) polarity is intricately linked to diverse biological processes and diseases. The visualization of LDs-polarity is of vital importance but challenging due to the lack of high-specificity, high-sensitivity and large-Stokes shift probes for real-time tracking LDs-polarity in biological systems. RESULTS: Four D-π-A based fluorescent probes (TPA-TCF1-TPA-TCF4) have been developed by combining tricyanofuran (an electron acceptor, A) and triphenylamine (an electron donor, D) derivatives with different terminal groups. Among them, TPA-TCF1 and TPA-TCF4 exhibit excellent polar sensitivity, large Stokes shift (≥182 nm in H2O), and efficient LDs targeting ability. In particular, TPA-TCF4 is capable of monitoring the change of LDs-polarity during ferroptosis, inflammation, apoptosis of cancer cell, and fatty liver. SIGNIFICANCE: All these features render TPA-TCF4 a versatile tool for pharmacodynamic evaluation of anti-cancer drugs, in-depth understanding of the biological effect of LDs on ferroptosis, and medical diagnosis of LDs-polarity related diseases.

How does carbon biased technological progress promote carbon haze collaborative Governance？Evidence from Chinese cities.

Carbon dioxide (CO2) emissions and haze pollution are often thought to have the same origin, the burning of fossil fuels. However, their relationship is not always synergistic and may even exhibit mutual constraints. Carbon-biased technological progress has emerged as a promising approach for simultaneously achieving three goals - to reduce CO2 emissions, alleviate the haze pressure, and keep economic growth. This study empirically investigates the impact and mechanisms of carbon-biased technological progress on carbon haze collaborative governance using data from 286 Chinese cities during 2006-2021. The results indicate that: (1) Carbon biased technological progress positively influences carbon haze collaborative governance. (2) This progress achieves coordination by enhancing element allocation efficiency, carbon efficiency, and responding to public environmental demands. (3) The facilitating role of carbon biased technological progress to carbon haze collaborative governance will work better if external conditions are met. Moreover, the effectiveness of carbon-biased technological progress in promoting coordination is contingent upon high levels of marketization, government intervention, environmental regulation, and technical advancements. Local and regional governments should foster conducive conditions for carbon dioxide and haze pollution coordination, optimize the allocation and flow of carbon resources, ensure harmonization between environmental regulation policies and other sectors, and bolster international cooperation and technical knowledge exchange to collectively address global environmental challenges.

Friend Emotional Support and Dynamics of Adolescent Socioemotional Problems.

Emotional support from friends is a crucial source of social support for adolescents, significantly influencing their psychological development. However, previous research has primarily focused on how this support correlates with general levels of socioemotional problems among adolescents, neglecting the significance of daily fluctuations in these problems. The aim of this study was to explore the relationship between friend emotional support and both the average and dynamic indicators of daily emotional and peer problems in adolescents. These dynamic indicators include within-domain dynamics-such as inertia, which reflects the temporal dependence of experiences, and volatility, which indicates within-person variance-and cross-domain dynamics, such as transactional effects, which measure the strength of concurrent or lagged associations between daily emotional and peer problems. Participants were 315 seventh-grade Chinese adolescents (Mage = 13.05 years, SD = 0.77 years; 48.3% girls). Adolescents reported on their friends' emotional support at baseline and then completed measures of daily emotion and peer problems over a 10-day period. Using dynamic structural equation models, the results revealed that higher levels of friend emotional support were associated with fewer daily socioemotional problems. This was evident both in terms of average levels and dynamic aspects, characterized by lower mean levels of daily emotional and peer problems, reduced inertia and volatility of these problems, and a weaker spillover effect from daily emotional issues to peer problems. These findings highlight the significant role of friend-emotional support in mitigating adolescents' daily socioemotional challenges.

A flexible, stretchable and wearable strain sensor based on physical eutectogels for deep learning-assisted motion identification.

Physical eutectogels as a newly emerging type of conductive gel have gained extensive interest for the next generation multifunctional electronic devices. Nevertheless, some obstacles, including weak mechanical performance, low self-adhesive strength, lack of self-healing capacity, and low conductivity, hinder their practical use in wearable strain sensors. Herein, lignin as a green filler and a multifunctional hydrogen bond donor was directly dissolved in a deep eutectic solvent (DES) composed of acrylic acid (AA) and choline chloride, and lignin-reinforced physical eutectogels (DESL) were obtained by the polymerization of AA. Due to the unique features of lignin and DES, the prepared DESL eutectogels exhibit good transparency, UV shielding capacity, excellent mechanical performance, outstanding self-adhesiveness, superior self-healing properties, and high conductivity. Based on the aforementioned integrated functions, a wearable strain sensor displaying a wide working range (0-1500%), high sensitivity (GF = 18.15), rapid responsiveness, and excellent stability and durability (1000 cycles) and capable of detecting diverse human motions was fabricated. Additionally, by combining DESL sensors with a deep learning technique, a gesture recognition system with accuracy as high as 98.8% was achieved. Overall, this work provides an innovative idea for constructing multifunction-integrated physical eutectogels for application in wearable electronics.

Correlation Between Coronal Position Sequence of Lumbar and WOMAC Score in Knee Osteoarthritis (KOA) in Standard Standing Position.

INTRODUCTION: Sagittal sequences of the spine have been shown to correlate with knee osteoarthritis (KOA), but coronal sequences and KOA have never been studied before. The study required patients to use a standard standing posture and aimed to explore the relationship between coronal position of lumbar spine and WOMAC score in KOA. METHODS: This is a cross-sectional observational study. Data on a total of 268 patients with KOA were collected. Patients were photographed in a standard standing position and lumbar-sacrum offset distance (L-SOD) and lumbar-knee offset distance (ΔL-KOD) were calculated. Patients were then divided into different groups according to different critical values and differences were compared. RESULTS: In the L-SOD of L1-3, WOMAC function (P = 0.021, P = 0.032, P = 0.001) and total score (P = 0.039, P = 0.034, P < 0.001) were different. In the L-SOD of L3-4, WOMAC pain score were different (P = 0.001, P = 0.032). At a cutoff of 13 mm, ΔL-KOD of L1-2 showed significant differences in pain part (P = 0.025, P = 0.039) and total score (P = 0.036, P = 0.050). There were significant differences in pain (P = 0.023, P = 0.027, P = 0.022), function (P = 0.048, P = 0.038, P = 0.047), and total score (P = 0.030, P = 0.027, P = 0.029) of L3-5. In the 18-mm cutoff group, only L1 and L2 have differences in the pain part (P = 0.050, P = 0.038). CONCLUSION: Coronal balance of the lumbar spine is associated with knee pain and function. The pelvis plays an important role in maintaining the coronal balance. Both the lumbar spine and the knee joint should be considered when developing the surgical strategy.

As a result of population aging, the number of patients suffering from both knee osteoarthritis (KOA) and degenerative diseases of the lumbar spine is increasing. It has been reported that patients with KOA have less symptomatic recovery after lumbar surgery, and that patients with lumbar degenerative disease have less symptomatic improvement after knee surgery than those without lumbar disease. So the knee and lumbar must be interacting in some way. Previous studies have confirmed the correlation between lumbar sagittal position sequence and KOA. However, no studies have been conducted on coronal sequences and KOA of the lumbar spine. We believe that it is because patients are required to stand naturally when taking coronal x-rays, and natural standing will lead to individual differences in the distance between the feet of patients, thereby preventing analysis. In our study, for the first time, we used a uniform stance to avoid this effect. The advantage of uniform stance is that individual differences can be excluded, and the same patient can be compared before and after treatment (because the natural stance of the patient's feet will be different before and after treatment), which is greatly conducive to the study. Our research found that the offset of the lumbar spine in the coronal position and the distance between the central vertical line of the lumbar spine and the bilateral knee joint are significantly correlated with knee pain and function. This may have some guiding significance for lumbar and knee surgery. For lumbar surgery (such as degenerative scoliosis), previous studies have suggested that short segment fixation is sufficient for patients with small Cobb angle. However, according to our conclusion, this may cause accelerated knee joint degeneration in the patient's later stages, which requires the surgeon to comprehensively evaluate the condition of the patient's knee and lumbar spine, and then formulate surgical strategies. The same is true for knee surgery: previous studies have shown no significant correlation between knee deformity and pain. Therefore, for patients with knee deformity and accompanying pain, knee surgery may not be the best choice, and it is more important to correct the deviation of the spine.

Prenatal prednisone exposure disturbs fetal kidney development and its characteristics.

Prednisone is a synthetic glucocorticoid that is commonly used in both human and veterinary medication. Now, it is also recognized as an emerging environmental contaminant. Pregnant women may be exposed to prednisone actively or passively through multiple pathways and cause developmental toxicity to the fetus. However, the impact of prenatal prednisone exposure (PPE) on fetal kidney development remains unclear. In this study, pregnant mice were administered prednisone intragastrically during full-term pregnancy with different doses (0.25, 0.5, or 1 mg/(kg·day)), or at the dose of 1 mg/(kg·day) in different gestational days (GD) (GD0-9, GD10-18, or GD0-18). The pregnant mice were euthanized on GD18. HE staining revealed fetal kidney dysplasia, with an enlarged glomerular Bowman's capsule space and a reduced capillary network in the PPE groups. The expression of the podocyte and the mesangial cell marker genes was significantly reduced in the PPE groups. However, overall gene expression in renal tubules and collecting ducts were markedly increased. All of the above effects were more pronounced in high-dose, full-term pregnancy, and female fetuses. Studies on the mechanism of the female fetal kidney have revealed that PPE reduced the expression of Six2, increased the expression of Hnf1ß, Hnf4α, and Wnt9b, and inhibited the expression of glial cell line-derived neurotrophic factor (GDNF) and Notch signaling pathways. In conclusion, this study demonstrated that there is a sex difference in the developmental toxicity of PPE to the fetal kidney, and the time effect is manifested as full-term pregnancy > early pregnancy > mid-late pregnancy.

Cu(II)-based complex loaded with drug paclitaxel hydrogels against thyroid cancer and optimizing novel derivatives.

This study introduces a novel approach for synthesizing a Cu(II)-based coordination polymer (CP), {[Cu(L)(4,4´-OBA)]·H2O}n (1), using a mixed ligand method. The CP was successfully prepared by reacting Cu(NO3)2·3H2O with the ligand 3,6-bis(benzimidazol-1-yl)pyridazine in the presence of 4,4´-H2OBA, demonstrating an innovative synthesis strategy. Furthermore, a novel hydrogel composed of hyaluronic acid (HA) and carboxymethyl chitosan (CMCS) with a porous structure was developed for drug delivery purposes. This hydrogel facilitates the encapsulation of CP1, and enables the loading of paclitaxel onto the composite to form HA/CMCS-CP1@paclitaxel. In vitro cell experiments demonstrated the promising modulation of thyroid cancer biomarker genes S100A6 and ARID1A by HA/CMCS-CP1@paclitaxel. Finally, reinforcement learning simulations were employed to optimize novel metal-organic frameworks, underscoring the innovative contributions of this study.

Receptor tyrosine kinase-like orphan receptor 1: A novel antitumor target in gastrointestinal cancers.

Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is a member of the type I receptor tyrosine kinase family. ROR1 is pivotal in embryonic development and cancer, and serves as a biomarker and therapeutic target. It has soluble and membrane-bound subtypes, with the latter highly expressed in tumors. ROR1 is conserved throughout evolution and may play a role in the development of gastrointestinal cancer through multiple signaling pathways and molecular mechanisms. Studies suggest that overexpression of ROR1 may increase tumor invasiveness and metastasis. Additionally, ROR1 may regulate the cell cycle, stem cell characteristics, and interact with other signaling pathways to affect cancer progression. This review explores the structure, expression and role of ROR1 in the development of gastrointestinal cancers. It discusses current antitumor strategies, outlining challenges and prospects for treatment.

Interpretable machine learning reveals microbiome signatures strongly associated with dairy cow milk urea nitrogen.

The gut microbiome plays an important role in the healthy and efficient farming of dairy cows. However, high-dimensional microbial information is difficult to interpret in a simplified manner. We collected fecal samples from 161 cows and performed 16S amplicon sequencing. We developed an interpretable machine learning framework to classify individuals based on their milk urea nitrogen (MUN) concentrations. In this framework, we address the challenge of handling high-dimensional microbial data imbalances and identify 9 microorganisms strongly correlated with MUN. We introduce the Shapley Additive Explanations (SHAP) method to provide insights into the machine learning predictions. The results of the study showed that the performance of the machine learning model improved (accuracy = 72.7%) after feature selection on high-dimensional data. Among the 9 microorganisms, g__Firmicutes_unclassified had the greatest impact in the model. This study provides a reference for precision animal husbandry.

TomoNet: A streamlined cryogenic electron tomography software pipeline with automatic particle picking on flexible lattices.

Cryogenic electron tomography (cryoET) is capable of determining in situ biological structures of molecular complexes at near-atomic resolution by averaging half a million subtomograms. While abundant complexes/particles are often clustered in arrays, precisely locating and seamlessly averaging such particles across many tomograms present major challenges. Here, we developed TomoNet, a software package with a modern graphical user interface to carry out the entire pipeline of cryoET and subtomogram averaging to achieve high resolution. TomoNet features built-in automatic particle picking and three-dimensional (3D) classification functions and integrates commonly used packages to streamline high-resolution subtomogram averaging for structures in 1D, 2D, or 3D arrays. Automatic particle picking is accomplished in two complementary ways: one based on template matching and the other using deep learning. TomoNet's hierarchical file organization and visual display facilitate efficient data management as required for large cryoET datasets. Applications of TomoNet to three types of datasets demonstrate its capability of efficient and accurate particle picking on flexible and imperfect lattices to obtain high-resolution 3D biological structures: virus-like particles, bacterial surface layers within cellular lamellae, and membranes decorated with nuclear egress protein complexes. These results demonstrate TomoNet's potential for broad applications to various cryoET projects targeting high-resolution in situ structures.