Characterization of active alkaloids and metabolites in rats after oral administration of Zuojin Pill using UHPLC-Q-TOF-MS combined with bioinformatics and molecular docking analyses.

Zuojin Pill (ZJP), a traditional Chinese medicine prescription composed of Rhizoma Coptidis and Euodiae Fructus in the ratio of 6:1 (w/w), has been widely used for the treatment of gastric disorders. However, an in-depth understanding of in vivo metabolism and distribution profiles of protoberberine alkaloids (PBAs) and indole alkaloids (IDAs) in ZJP is lacking. In this study, a method using ultra-high performance liquid chromatography coupled with quadruple time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) was developed to systematically screen the alkaloids and their metabolites in rat plasma and various tissues after oral administration of ZJP. Furthermore, bioinformatics and molecular docking analyses were conducted to elucidate the contribution of the alkaloids and metabolites enriched in the stomach to the therapeutic effect of ZJP on gastritis. A total of 33 compounds, including 7 prototype alkaloids and 26 metabolites, were chemically defined or tentatively identified in this work. The metabolic pathways of PBAs (hydroxylation, oxidation, reduction, demethylation, demethylenation, glucuronide conjugation, sulfate conjugation) and IDAs (hydroxylation, glucuronide conjugation) were revealed. Notably, 7 prototype alkaloids and 18 metabolites were detected in the stomach, indicating their propensity for gastric distribution. These alkaloids and metabolites showed strong affinities with the 7 hub targets associated with gastritis, such as CCR7, CXCR4, IL6, IFNG, CCL2, TNF, and PTPRC, and could be considered the potential active substances of ZJP for treating gastritis. In conclusion, this study clarified the gastric distribution propensity of PBAs and IDAs and their metabolites, as well as their favorable binding interactions with gastritis-related targets, which could provide essential data for the further study of the pharmacodynamic material basis and gastroprotective mechanism of ZJP.

Association between tobacco exposure and bladder cancer recurrence: A systematic review and meta-analysis.

BACKGROUND: However, the connection between smoking and the prognosis of patients with bladder cancer remains unclear. AIM: To determine whether smoking is linked to the recurrence and progression of bladder cancer. METHODS: As of July 20, 2022, relevant English-language research was identified by searching PubMed, the Web of Science, and the Cochrane Library. We pooled the available data from the included studies using a random effects model. Subgroup analysis and sensitivity analysis were also conducted. RESULTS: A total of 12 studies were included in this meta-analysis. The combined analysis revealed that tobacco exposure was associated with a significantly greater recurrence rate than nonsmoking status [odd ratios (OR) = 1.76, 95%CI: 1.84-2.93], and the progression of bladder cancer was significantly greater in smokers than in nonsmokers (OR = 1.21, 95%CI: 1.02-1.44). Stratified analysis further revealed that current smokers were more likely to experience relapse than never-smokers were (OR = 1.85, 95%CI: 1.11-3.07). Former smokers also had a greater risk of relapse than did never-smokers (OR = 1.73, 95%CI: 1.09-2.73). Subgroup analysis indicated that non-Caucasians may be more susceptible to bladder cancer recurrence than Caucasians are (OR = 2.13, 95%CI: 1.74-2.61). CONCLUSION: This meta-analysis revealed that tobacco exposure may be a significant risk factor for both the recurrence and progression of bladder cancer.

The lowdown on breakdown: Open questions in plant proteolysis.

Proteolysis, including post-translational proteolytic processing as well as protein degradation and amino acid recycling, is an essential component of the growth and development of living organisms. In this article, experts in plant proteolysis pose and discuss compelling open questions in their areas of research. Topics covered include the role of proteolysis in the cell cycle, DNA damage response, mitochondrial function, the generation of N-terminal signals (degrons) that mark many proteins for degradation (N-terminal acetylation, the Arg/N-degron pathway, and the chloroplast N-degron pathway), developmental and metabolic signaling (photomorphogenesis, abscisic acid and strigolactone signaling, sugar metabolism, and post-harvest regulation), plant responses to environmental signals (endoplasmic-reticulum associated degradation, chloroplast-associated degradation, drought tolerance, the growth-defense tradeoff)), and the functional diversification of peptidases. We hope these thought-provoking discussions help to stimulate further research.

A laponite-based immunologically active gel delivery system for long-acting tumor vaccine.

Traditional bolus vaccines typically require multiple doses, which complicates the vaccination process and may cause missed shots, leading to sub-optimal immunity and reduced vaccine effectiveness. Herein, a gel-based long-acting vaccine system with self-adjuvant properties based on laponite was constructed to simplify vaccination procedures and improve vaccine effectiveness. Firstly, the gel system could recruit multiple types of immune cells to form immune niches. Secondly, it could achieve sustained delivery of antigens to lymph nodes by active transport and passive drainage. Then, the gel system triggered the formation of a large number of germinal centers, which elicited enhanced and durable humoral immune responses, as well as strong cellular immune responses. As a result, it eventually showed good prophylactic and therapeutic effects in a variety of tumor models including melanoma, colorectal cancer and peritoneal metastasis models. By further combining the immunoadjuvant CpG ODN and cytokine IL-12, the effect of the gel-vaccine could be further enhanced. In a murine peritoneal metastasis model of colorectal carcinoma, a single administration of the gel-vaccine resulted in complete tumor eradication in 8/9 mice. In summary, this study developed an immunologically active gel-vaccine system. And as a robust and versatile vaccine platform, by loading different antigens and adjuvants, this gel-vaccine system is expected to realize its better therapeutic potential.

Gene expression profiles to clarify the effect of low-dose benzo(a)pyrene on crystalline silica induced acute lung injury in mice.

Published evidences have suggested that air pollutant benzo(a)pyrene (BaP) may modify the toxicity and adverse effects produced by other toxicants. However, the precise role of short-term exposure to low-dose BaP on acute lung injury (ALI) induced by crystalline silica (CS) and the underlying mechanisms remain to be clarified. To investigate this issue, a mouse co-exposure model was established by intratracheal instillation of 2.5 mg CS and BaP alone or in combination. Our data found that CS exposure resulted in ALI as evidenced by lung histological changes, elevated lactate dehydrogenase activity, increased level of pro-inflammatory markers and enhanced oxidative damage. Although exposure to BaP alone had little effect on the pathological changes of mice lung tissues except for occasionally mild inflammation, it could aggravate the CS-induced ALI in a dose-dependent manner. Bioinformatic analysis of transcriptome sequencing suggested that the expression changes of significantly differentially expressed genes were closely related to the severity of ALI. The joined analysis of STC and WGCNA found that "NOD-like receptor signaling pathway", "toll-like receptor signaling pathway", "TNF signaling pathway", and "NF-kappa B signaling pathway" associated with immune and inflammatory response were the most prominent significant pathways. TLR2/9 and Nod2 might be the key inflammation-related genes that were differentially expressed in the combined lung toxicity induced by CS and BaP exposure. All these findings suggest that co-exposure of CS and low-dose BaP can cause more severe lung inflammation and oxidative damage in mice than exposure alone, which may be useful in the management and prevention of silicosis. The roles of TLR2/9 and Nod2 as candidate targets in the combined toxicity need further exploration.

Mechanistic insights into phosphoactivation of SLAC1 in guard cell signaling.

Stomata in leaves regulate gas (carbon dioxide and water vapor) exchange and water transpiration between plants and the atmosphere. SLow Anion Channel 1 (SLAC1) mediates anion efflux from guard cells and plays a crucial role in controlling stomatal aperture. It serves as a central hub for multiple signaling pathways in response to environmental stimuli, with its activity regulated through phosphorylation via various plant protein kinases. However, the molecular mechanism underlying SLAC1 phosphoactivation has remained elusive. Through a combination of protein sequence analyses, AlphaFold-based modeling and electrophysiological studies, we unveiled that the highly conserved motifs on the N- and C-terminal segments of SLAC1 form a cytosolic regulatory domain (CRD) that interacts with the transmembrane domain(TMD), thereby maintaining the channel in an autoinhibited state. Mutations in these conserved motifs destabilize the CRD, releasing autoinhibition in SLAC1 and enabling its transition into an activated state. Our further studies demonstrated that SLAC1 activation undergoes an autoinhibition-release process and subsequent structural changes in the pore helices. These findings provide mechanistic insights into the activation mechanism of SLAC1 and shed light on understanding how SLAC1 controls stomatal closure in response to environmental stimuli.

An intelligent spraying system for weeds in wheat fields based on a dynamic model of droplets impacting wheat leaves.

Introduction: Targeted herbicide application refers to precise application of herbicides in weed-infested areas according to the location and density of farmland weeds. At present, targeted herbicide application in wheat fields generally faces problems including the low herbicide adhesion rate, leading to omission and excessive loss of herbicides. Methods: To solve these problems, changes in the impact force of herbicide and the weed leaves in the operation process of a spraying system were studied from the interaction between weeds and herbicides applied. A dynamic model of weed leaves was established. On this basis, the research indicated that the herbicide adhesion rate is highest under spraying pressure of 0.4 MPa and flow rate of 0.011 kg/s when the spray height is 300 mm. To study the dynamic deformation of weed leaves and the distribution of liquid herbicides in the external flow field under weed-herbicide interaction, a dynamic simulation model of herbicide application was built using the finite element method. Results and Discussion: The results show that when the spray height is 300 mm, the maximum weed leaf deformation index (LDI) is 0.43 and the velocity in the external flow field is 0 m/s under spraying pressure of 0.4 MPa and flow rate of 0.011 kg/s. This finding indicates that the herbicide is not splashed elsewhere and the turbulence intensity in the weed area is 2%, implying steady flow of the herbicide, most of which can be retained on weed leaves. Field test results of application quality of the herbicide show that the maximum LDI is 0.41 and the coverage of the herbicide in the sheltered area below the leaves is 19.02% when the spraying pressure is 0.4 MPa, flow rate is 0.011 kg/s, and spray height is 300 mm. This solves the problem of a low rate of utilization of herbicides because the herbicide passes through weed plants, and achieves the precision herbicide application in wheat fields.

Effect of Luhong formula on the cardiac rehabilitation of patients with chronic heart failure.

BACKGROUND: Current treatments for chronic heart failure (CHF) are therapeutically ineffective. The optimization of treatments for this disease needs to be explored and analyzed. AIM: To analyze the effect of using Luhong Formula in the cardiac rehabilitation of patients with CHF and its influence on cardiopulmonary function (CPF) and prognosis. METHODS: In total, 160 patients with CHF admitted between June 2022 and June 2023 were selected, including 75 receiving perindopril (control group) and 85 receiving Luhong Formula (research group). We conducted comparative analyses on the curative effects of traditional Chinese medicine (TCM) syndromes and cardiac function, CPF [oxygen consumption at the anaerobic threshold (VO2 AT) and at peak exercise (peak VO2)], echocardiographic indexes [left atrial volume index (LAVI), left ventricular muscle mass index (LVMI), left ventricular ejection fraction (LVEF)], and prognosis [major adverse cardiovascular events (MACEs) at 6 months follow-up]. RESULTS: The research group showed markedly higher curative effects of TCM syndromes and cardiac function than the control group. In addition, post-treatment VO2 AT, peak VO2, LVMI and LVEF in the research group were significantly higher, whereas LAVI was significantly lower, than those of the control group. Furthermore, fewer patients in the research group developed MACEs at the 6-month follow-up. CONCLUSION: Luhong Formula is more therapeutically effective than perindopril for the cardiac rehabilitation of patients with CHF, specifically in enhancing CPF and prognosis.

Comparison of Long-Term Clinical Outcomes and Costs Between Transesophageal Echocardiography-Guided and X-ray-Guided Percutaneous Atrial Septal Defect Closure in Children.

This study aimed to compare the long-term clinical outcomes and costs between using either transesophageal echocardiography (TEE) or X-ray fluoroscopy for Percutaneous atrial septal defect (ASD) closure in children. An analysis was conducted on clinical data from children undergoing TEE-guided (n = 168) and X-ray-guided (n = 139) percutaneous ASD closure. Demographic characteristics, technical indices, acute complications, follow-up outcomes, and costs were compared between the groups. The results are that TEE-guided closure demonstrated shorter surgical times (20.3 ± 7.6 min vs. 32.8 ± 7.9 min, P < 0.001) and lower procedural costs ($3093.3 ± 451.5 vs. $3589.1 ± 219.4, P < 0.001) compared to X-ray guidance. Initial successful closure rates were similar between the groups (TEE: 98.2%, XR: 97.1%, P = 0.691). TEE guidance also resulted in fewer acute complications and reduced radiation exposure. TEE-guided percutaneous ASD closure offers advantages in terms of shorter surgical times, lower procedural costs, and reduced radiation exposure compared to X-ray guidance. These findings support the preference for TEE guidance in pediatric ASD closure procedures, with potential implications for improving patient outcomes and reducing healthcare costs.

Incidence and clinical analysis of asymptomatic intracranial hemorrhage in neonates with cerebral hypoxic-ischaemic risk based on multisequence MR images.

The incidence and clinical distribution of intracranial haemorrhage (ICH) in neonates at risk of cerebral hypoxia-ischaemia have not been reported in specific studies. Based on conventional magnetic resonance imaging (MRI) versus susceptibility weighted imaging (SWI), this study aimed to analyse the occurrence of asymptomatic ICH in newborns with or without risk of cerebral hypoxia-ischaemia and to accumulate objective data for clinical evaluations of high-risk neonates and corresponding response strategies. 317 newborns were included. MRI revealed that the overall incidence of ICH was 59.31%. The most common subtype was intracranial extracerebral haemorrhage (ICECH) which included subarachnoid haemorrhage (SAH) and subdural haemorrhage (SDH). ICECH accounted for 92.02% of ICH. The positive detection rate of ICECH by SWI was significantly higher than that by T1WI. The incidence of total ICH, ICECH and SAH was greater among children who were delivered vaginally than among those who underwent caesarean delivery. Asymptomatic neonatal ICH may be a common complication of the neonatal birth process, and SWI may improve the detection rate. Transvaginal delivery and a weight greater than 2500 g were associated with a high incidence of ICECH in neonates. The impact of neonatal cerebral hypoxia-ischaemia risk factors on the occurrence of asymptomatic ICH may be negligible.

Evaluation of Neonatal Cerebral Circulation Under Hypoxic Ischemic Risk Factors Based on Quantitative Analysis of Cerebral Veins with Magnetic Resonance Susceptibility Weighted Imaging.

PURPOSE: To observe the regulation of cerebral circulation in vivo based on image segmentation algorithms for deep learning in medical imaging to automatically detect and quantify the neonatal deep medullary veins (DMVs) on susceptibility weighted imaging (SWI) images. To evaluate early cerebral circulation self-rescue for neonates undergoing risk of cerebral hypoxia-ischaemia in vivo. METHODS: SWI images and clinical data of 317 neonates with or without risk of cerebral hypoxia-ischaemia were analyzed. Quantitative parameters showing the number, width, and curvature of DMVs were obtained using an image segmentation algorithm. RESULTS: The number of DMVs was greater in males than in females (p < 0.01), and in term than in preterm infants (p = 0.001). The width of DMVs was greater in term than in preterm infants (p < 0.01), in low-risk than in high-risk group (p < 0.01), and in neonates without intracranial extracerebral haemorrhage (ICECH) than with ICECH (p < 0.05). The curvature of DMVs was greater in term than in preterm infants (P < 0.05). The width of both bilateral thalamic veins and anterior caudate nucleus veins were positively correlated with the number of DMVs; the width of bilateral thalamic veins was positively correlated with the width of DMVs. CONCLUSION: The DMVs quantification based on image segmentation algorithm may provide more detailed and stable quantitative information in neonate. SWI vein quantification may be an observable indicator for in vivo assessment of cerebral circulation self-regulation in neonatal hypoxic-ischemic brain injury.

Meta-analysis of the clinical efficacy and safety of single versus dual plate in the treatment of comminuted distal femur fractures.

Objective: Through meta-analysis, this study aims to comprehensively evaluate the efficacy of single-plating and double-plating in the treatment of comminuted fractures of the distal femur. Methods: Computer searches of PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), China Biology Medicine (CBM), VIP, and Wanfang digital journals were performed, and the timeframe for the searches was from the establishment of each database to July 2023 for each of the databases. Meta-analysis was performed using RevMan 5.4 software provided by the Cochrane Library, and the review process was registered in the PROSPERO database. Results: A total of ten studies were included for statistical analysis. One randomised controlled study and nine retrospective cohort studies with a total of 563 patients were included. The double-plate group was superior to the single-plate group in terms of knee mobility at 6 months postoperatively, overall postoperative complications, and the rate of healing of knee deformity. However, it increased the operation time and intraoperative bleeding, and the difference between the two groups was statistically significant (P < 0.05). There was no significant difference between the two groups in terms of excellent knee function rate, fracture healing time, plate fracture, postoperative infection, delayed fracture healing, and non-union (P ≥ 0.05). Conclusion: Double plate fixation for comminuted fractures of the distal femur can improve knee mobility at 6 months postoperatively, reduce overall postoperative complications, and decrease the incidence of malunion healing. However, it increases operative time and bleeding. Randomised studies are needed to provide strong evidence in the future.

Deficiency of CAMSAP2 impairs olfaction and the morphogenesis of mitral cells.

In developing olfactory bulb (OB), mitral cells (MCs) remodel their dendrites to establish the precise olfactory circuit, and these circuits are critical for individuals to sense odors and elicit behaviors for survival. However, how microtubules (MTs) participate in the process of dendritic remodeling remains elusive. Here, we reveal that calmodulin-regulated spectrin-associated proteins (CAMSAPs), a family of proteins that bind to the minus-end of the noncentrosomal MTs, play a crucial part in the development of MC dendrites. We observed that Camsap2 knockout (KO) males are infertile while the reproductive tract is normal. Further study showed that the infertility was due to the severe defects of mating behavior in male mice. Besides, mice with loss-of-function displayed defects in the sense of smell. Furthermore, we found that the deficiency of CAMSAP2 impairs the classical morphology of MCs, and the CAMSAP2-dependent dendritic remodeling process is responsible for this defect. Thus, our findings demonstrate that CAMSAP2 plays a vital role in regulating the development of MCs.

Identification of Curcumin Targets in the Brain of Epileptic Mice Using DARTS.

Curcumin, a compound derived from turmeric, is traditionally utilized in East Asian medicine for treating various health conditions, including epilepsy. Despite its involvement in numerous cellular signaling pathways, the specific mechanisms and targets of curcumin in epilepsy treatment have remained unclear. Our study focused on identifying the primary targets and functional pathways of curcumin in the brains of epileptic mice. Using drug affinity responsive target stabilization (DARTS) and affinity chromatography, we identified key targets in the mouse brain, revealing 232 and 70 potential curcumin targets, respectively. Bioinformatics analysis revealed a strong association of these proteins with focal adhesions and cytoskeletal components. Further experiments using DARTS, along with immunofluorescence staining and cell migration assays, confirmed curcumin's ability to regulate the dynamics of focal adhesions and influence cell migration. This study not only advances our understanding of curcumin's role in epilepsy treatment but also serves as a model for identifying therapeutic targets in neurological disorders.

Recyclable Au@R-Fe3O4/g-C3N4 substrates for rapid SERS detection and degradation of multiple pollutants.

Developing a Surface-enhanced Raman spectroscopy (SERS) method with excellent detecting ability, good recyclability and analyzing multiple pollutants rapidly are critical for evaluation of water quality in emergency pollution affairs. While constructing a multifunctional substrate with these characteristics to realize the application of SERS in water quality monitoring remains a challenge. In this work, a reusable Au@R-Fe3O4/g-C3N4 SERS substrate is prepared by loading Au nanoparticles (Au NPs) on Fe3O4 nanorings (R-Fe3O4) and the formed Au@R-Fe3O4 is further combined with g-C3N4 nanosheets through a simple electrostatic assembly method. The Au@R-Fe3O4/g-C3N4 nanocomposite presents multifunction of magnetic enrichment, SERS signal enhancement, multiple pollutants analyzing, and photocatalytic activity, which achieves quantitative detection of rhodamine B (RhB), tetracycline hydrochloride (TC), and 4-chlorophenol (4-CP), with detection limits of 5.30 × 10-9, 7.50 × 10-8, 7.69 × 10-8 mol/L, respectively. Furthermore, the recyclable detection capability of Au@R-Fe3O4/g-C3N4 for multi components is demonstrated by the strong SERS signal after 9 cycles of "detection-degradation" processes. Combined with good uniformity and stability, this SERS method based on Au@R-Fe3O4/g-C3N4 substrate provides a new strategy for the multi-pollutants detection and degradation in water environment.

Construction of 5-Fluorouracil and Gallium Corrole Conjugates for Enhanced Photodynamic Therapy.

Molecular hybridization is a well-established strategy for developing new drugs. In the pursuit of promising photosensitizers (PSs) with enhanced photodynamic therapy (PDT) efficiency, a series of novel 5-fluorouracil (5FU) gallium corrole conjugates (1-Ga-4-Ga) were designed and synthesized by hybridizing a chemotherapeutic drug and PSs. Their photodynamic antitumor activity was also evaluated. The most active complex (2-Ga) possesses a low IC50 value of 0.185 µM and a phototoxic index of 541 against HepG2 cells. Additionally, the 5FU-gallium corrole conjugate (2-Ga) exhibited a synergistic increase in cytotoxicity under irradiation. Excitedly, treatment of HepG2 tumor-bearing mice with 2-Ga under irradiation could completely ablate tumors without harming normal tissues. 2-Ga-mediated PDT could disrupt mitochondrial function, cause cell cycle arrest in the sub-G1 phase, and activate the cell apoptosis pathway by upregulating the cleaved PARP expression and the Bax/Bcl-2 ratios. This work provides a useful strategy for the design of new corrole-based chemo-photodynamic therapy drugs.

Release of a ubiquitin brake activates OsCERK1-triggered immunity in rice.

Plant pattern-recognition receptors perceive microorganism-associated molecular patterns to activate immune signalling1,2. Activation of the pattern-recognition receptor kinase CERK1 is essential for immunity, but tight inhibition of receptor kinases in the absence of pathogen is crucial to prevent autoimmunity3,4. Here we find that the U-box ubiquitin E3 ligase OsCIE1 acts as a molecular brake to inhibit OsCERK1 in rice. During homeostasis, OsCIE1 ubiquitinates OsCERK1, reducing its kinase activity. In the presence of the microorganism-associated molecular pattern chitin, active OsCERK1 phosphorylates OsCIE1 and blocks its E3 ligase activity, thus releasing the brake and promoting immunity. Phosphorylation of a serine within the U-box of OsCIE1 prevents its interaction with E2 ubiquitin-conjugating enzymes and serves as a phosphorylation switch. This phosphorylation site is conserved in E3 ligases from plants to animals. Our work identifies a ligand-released brake that enables dynamic immune regulation.

Rational Design of Coumarin-Based Hybridized Local and Charge-Transfer Blue Emitters for Solution-Processed Organic Light-Emitting Diodes.

Hybridized local and charge-transfer (HLCT) with the utilization of both singlet and triplet excitons through the "hot excitons" channel have great application potential in highly efficient blue organic light-emitting diodes (OLEDs). The proportion of charge-transfer (CT) and locally excited (LE) components in the relevant singlet and triplet states makes a big difference for the high-lying reverse intersystem crossing process. Herein, three novel donor (D)-acceptor (A) type HLCT materials, 7-([1,1'-biphenyl]-4-yl(9,9-dimethyl-9H-fluoren-2-yl)amino)-3-phenyl-1H-isochromen-1-one (pPh-7P), 7-([1,1'-biphenyl]-4-yl(9,9-dimethyl-9H-fluoren-2-yl)amino)-3-methyl-1H-isochromen-1-one (pPh-7M), and 6-([1,1'-biphenyl]-4-yl(9,9-dimethyl-9H-fluoren-2-yl)amino)-3-methyl-1H-isochromen-1-one (pPh-6M), were rationally designed and synthesized with diphenylamine derivative as donor and oxygen heterocyclic coumarin moiety as acceptors. The proportions of CT and LE components were fine controlled by changing the connection site of diphenylamine derivative at C6/C7-position and the substituent at C3-position of coumarin moiety. The HLCT characteristics of pPh-7P, pPh-7M, and pPh-6M were systematically demonstrated through photophysical properties and density functional theory calculations. The solution-processed doped OLEDs based on pPh-6M exhibited deep-blue electroluminescence with the maximum emission wavelength of 446 nm, maximum luminance of 8755 cd m-2, maximum current efficiency of 5.83 cd A-1, and maximum external quantum efficiency of 6.54 %. The results reveal that pPh-6M with dominant 1LE and 3CT components has better OLED performance.

Phosphorylation of 399S at CsHsp70 of Cymbidium sinense is essential to maintain chlorophyll stability.

The Chinese orchids symbolise nobility and gentility in China, and the variation of leaf color makes Cymbidium sinense more diversified and valuable. However, its color variations especially at the protein level still remain largely unexplored. In this study, the proteomics and phosphoproteomics of Cymbidium sinense leaf color variation mutants were studied. A total of 1059 differentially abundant proteins (DAPs) and 1127 differentially abundant phosphorylation sites belonging to 644 phosphoproteins (DAPPs) were identified in the yellow section of leaf variegation mutant of Cymbidium sinense (MY) compared with the green section (MG). Moreover, 349 co-expressing proteins were found in both omics' datasets, while only 26 proteins showed the same expression patterns in the two omics. The interaction network analysis of kinases and phosphatases showed that DAPs and DAPPs in photosynthesis, response to hormones, pigment metabolic process, phosphorylation, glucose metabolic process, and dephosphorylation might contribute to leaf color variation. The abundance of 28 Hsps and 28 phosphorylation sites belonging to 10 Hsps showed significant differences between MG and MY. CsHsp70 was selected to explore the function in Cymbidium sinense leaf variegation. The results showed CsHsp70 is essential for maintaining photosynthetic pigment content and the 399S phosphorylation site is crucial to the function of CsHsp70. Collectively, our findings construct a comprehensive coverage of protein and protein phosphorylation in leaf variegation of C. sinense, providing valuable insights into its formation mechanisms.

Molecular targets and mechanisms of different aberrant alternative splicing in metastatic liver cancer.

Metastasis remains a major challenge in the successful management of malignant diseases. The liver is a major site of metastatic disease and a leading cause of death from gastrointestinal malignancies such as colon, stomach, and pancreatic cancers, as well as melanoma, breast cancer, and sarcoma. As an important factor that influences the development of metastatic liver cancer, alternative splicing drives the diversity of RNA transcripts and protein subtypes, which may provide potential to broaden the target space. In particular, the dysfunction of splicing factors and abnormal expression of splicing variants are associated with the occurrence, progression, aggressiveness, and drug resistance of cancers caused by the selective splicing of specific genes. This review is the first to provide a detailed summary of the normal splicing process and alterations that occur during metastatic liver cancer. It will cover the role of alternative splicing in the mechanisms of metastatic liver cancer by examining splicing factor changes, abnormal splicing, and the contribution of hypoxia to these changes during metastasis.