Blood-responsive mussel-inspired hydrogels for hemostasis, antibacterial action, and wound healing.

Rapid hemostasis, potent antimicrobial activity, and efficient wound management are critical factors in enhancing the survival of trauma patients. Chitosan, as a green and sustainable biomaterial with low cost, degradability and biocompatibility, is widely used in the biomedical field. However, chitosan dissolves in an acidic environment, which is not conducive to wound healing. In this study, chitosan was chemically modified to address this limitation. A mussel-inspired hydrogel composed of caffeic acid-grafted chitosan, gallic acid-grafted chitosan, and oxidized microcrystalline cellulose (CHI-C/CSG/OMCC) was designed. This hydrogel exhibits blood-responsive gelation behavior and offers a synergistic combination of tissue adhesion, antimicrobial properties, and tissue repair capabilities. The carboxyl, hydroxyl, phenolic hydroxyl and aldehyde groups within the hydrogel system endowed the hydrogel with excellent adhesion properties (53.1 kPa adhesion strength to porcine skin-adherent tissues), biocompatibility, and excellent antimicrobial properties. Surprisingly, this hydrogel not only achieved rapid and effective hemostasis, but also effectively promoted wound healing in a mouse skin injury model. In addition, its remarkable efficacy in stopping bleeding within approximately 2 min without rebleeding was demonstrated in a porcine model of acute gastrointestinal hemorrhage in the esophagus, stomach, and intestines. This blood-responsive ternary hydrogel offers a promising alternative to wound management materials due to its excellent overall performance and superior efficacy in all phases of wound healing.

TET1 overexpression affects cell proliferation and apoptosis in aging ovaries.

PURPOSE: Along with the progress of society, human life expectancy has been increasing, and late marriage and late childbearing are the current trend. Since reproductive aging affects fertility, ovarian aging in women has become a major reproductive health issue in the current society. During ovarian aging, DNA methylation levels may change. The ten-eleven translocation (TET) protein family proteins TET1, TET2, and TET3 are important DNA demethylation enzymes, and differential expression of TET1, TET2, and TET3 may affect the proliferation and apoptosis of aging ovarian cells. The aim of this study was to investigate the role of TET1 in the regulation of ovarian aging. METHODS: The expression of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) was analyzed by immunofluorescence (IF) in young and aging ovaries of six 6-8-week-old female mice and six 6-8-month-old female mice. Then, the expression pattern of the TET protein family in young and aging ovaries of mice was investigated. To determine the impact of TET1 on ovarian development, the aging of IOSE-80, KGN, and SKOV-3 cells was induced with D-galactosidase (D-gal). Cells were then transfected using the TET1 overexpression vector or si-TET1. We assessed the proliferation and apoptosis of aging cells after transfection and analyzed the regulatory effect of TET1 expression on aging cells. Additionally, we verified the Tet1 expression in Tet1-KO mice. RESULTS: The 5mC to 5hmC transition, oocyte maturation, and blastocyst rate were reduced in aging mice compared to young mice. In aging mice ovaries, the expression levels of Tet1, Tet2, and Tet3 were reduced significantly, with Tet1 being particularly pronounced. The overexpression of TET1 promoted proliferation and inhibited apoptosis in aging human ovarian cells. Furthermore, Tet1 expression was very low in Tet1-KO C57BL/6 J mice ovaries. CONCLUSION: This study demonstrates that the expression levels of TET family proteins are low in aging ovaries, and the overexpression of TET1 can promote proliferation and inhibit apoptosis in aging ovarian cells.

The correlation of inflammation, tryptophan-kynurenine pathway, and suicide risk in adolescent depression.

Accumulating evidence suggests a role for the tryptophan-kynurenine pathway (TKP) in the psychopathology of major depressive disorder (MDD). Abnormal inflammatory profile and production of TKP neurotoxic metabolites appear more pronounced in MDD with suicidality. Progress in understanding the neurobiology of MDD in adolescents lags significantly behind that in adults due to limited empirical evidence. Aims of this study was to investigate the association between inflammation, TKP, and suicidality in adolescent depression. Seventy-three adolescents with MDD were assessed for serum levels of interleukin (IL)-1ß, IL-6, IL-18, IL-10, tumor necrosis factor-α (TNF-α), tryptophan (TRP), kynurenine (KYN), 3-hydroxykynurenine (3-HK), and kynurenine acid (KA). Correlations between cytokines and TKP measures were examined. Patients were divided into high- (n = 42) and non-high-suicide-risk groups (n = 31), and serum levels of cytokines and TKP metabolites were compared. Significant negative correlations were found between TRP and IL-8 (r = - 0.27, P < 0.05) and IL-10 (r = - 0.23, P < 0.05), while a significant positive correlation was observed between 3-HK and IL-8 (r = 0.39, P < 0.01) in depressed adolescents. The KYN/TPR (index of indoleamine 2,3-dioxygenase, IDO) was positively correlated with IL-1ß (r = 0.34), IL-6 (r = 0.32), IL-10 (r = 0.38) and TNF-α (r = 0.35) levels (P < 0.01); and 3-HK/KYN (index of kynurenine3-monooxidase, KMO) was positively correlated with IL-8 level (r = 0.31, P < 0.01). Depressed adolescents at high suicide risk exhibited significantly higher levels of IL-1ß (Z = 2.726, P < 0.05), IL-10 (Z = 2.444, P < 0.05), and TNF-α (Z = 2.167, P < 0.05) and lower levels of 3-HK (Z = 2.126, P < 0.05) compared to their non-high suicide risk counterparts. Our findings indicated that serum inflammatory cytokines were robustly associated with IDO and KMO activity, along with significantly decreased serum level of TRP, increased level of 3-HK, and higher suicide risk in adolescent depression.

Hierarchical structures and magnetism of Co clusters: a perspective from integration of deep learning and a hybrid differential evolution algorithm.

Theoretically determining the lowest-energy structure of a cluster has been a persistent challenge due to the inherent difficulty in accurate description of its potential energy surface (PES) and the exponentially increasing number of local minima on the PES with the cluster size. In this work, density-functional theory (DFT) calculations of Co clusters were performed to construct a dataset for training deep neural networks to deduce a deep potential (DP) model with near-DFT accuracy while significantly reducing computational consumption comparable to classic empirical potentials. Leveraging the DP model, a high-efficiency hybrid differential evolution (HDE) algorithm was employed to search for the lowest-energy structures of CoN (N = 11-50) clusters. Our results revealed 38 of these clusters superior to those recorded in the Cambridge Cluster Database and identified diverse architectures of the clusters, evolving from layered structures for N = 11-27 to Marks decahedron-like structures for N = 28-42 and to icosahedron-like structures for N = 43-50. Subsequent analyses of the atomic arrangement, structural similarity, and growth pattern further verified their hierarchical structures. Meanwhile, several highly stable clusters, i.e., Co13, Co19, Co22, Co39, and Co43, were discovered by the energetic analyses. Furthermore, the magnetic stability of the clusters was verified, and a competition between the coordination number and bond length in affecting the magnetic moment was observed. Our study provides high-accuracy and high-efficiency prediction of the optimal structures of clusters and sheds light on the growth trend of Co clusters containing tens of atoms, contributing to advancing the global optimization algorithms for effective determination of cluster structures.

[Effect of Flow Cytometric MRD Detection at Different Time Points during AML Chemotherapy on Prognosis].

OBJECTIVE: To investigate the effect of flow cytometric minimal residual disease (MRD) detection at different time points during AML chemotherapy on prognosis. METHODS: 130 adult primary AML patients diagnosed and standardized with chemotherapy from March 2018 to March 2022 were retrospectively analyzed, MRD was detected by flow cytometry, Kaplan-Meier curves was used for survival analysis and log-rank test was used for variance analysis, and univariate and multifactor influencing patient survival with COX proportional risk regression model analysis. Cumulative incidence rate (CIR) analysis with competing risk model and variance analysis using Fine-Gray. RESULTS: There were 81 CR1, 26 CR2, 14 PR, and 9 NR patients in 130 patients. OS of the CR1 group was higher than that in the CR2, PR,and NR groups. OS of the CR2 group was higher than that in the PR group, but there was no statistically difference compared to the NR group. There was no statistically difference in OS between the PR and NR groups. 107 patients in CR1 and CR2 were grouped according to MRD detected by flow cytometry, and after the first induction chemotherapy, for patients in the MRD- and MRD+ groups, the 4-year expected RFS rates were 65.3% and 27.9% respectively, the 4-year expected OS rates were 58.7% and 41.4% respectively, and the 4-year expected CIR were 34.7% and 69.7% respectively, with statistically significant differences between 2 groups (χ2=6.639, P =0.010; χ2=6.131, P =0.013 and χ2=6.637， P =0.010). After the second chemotherapy, for patients in the MRD- and MRD+ groups, the 4-year expected RFS rates were 50.8% and 37.9% respectively, the 4-year expected OS rates were 49.2% and 44.5% respectively, and the 4-year expected CIR were 49.2% and 59.5% respectively, with no statistically significant differences between 2 groups (χ2=1.475, P =0.225; χ2=2.432, P =0.119 and χ2=1.416， P =0.234). During consolidation therapy, for patients in the MRD - and MRD+ groups, the 4-year expected RFS rates were 51.9% and 29.6% respectively, the 4-year expected OS rates were 67.5% and 24.6% respectively, and the 4-year expected CIR were 48.1% and 70.4% respectively, with statistically significant differences between 2 groups (χ2=20.982, P < 0.001; χ2=17.794, P < 0.001 and χ2=19.879， P < 0.001). For patients with MRD- at all three time points and positive at either time point, the 4-year expected RFS rates were 69.9% and 33.3% respectively, the 4-year expected OS rates were 59.1% and 44.7% respectively, and the 4-year expected CIR were 30.1% and 65.1% respectively, with statistically significant differences between 2 groups (χ2=7.367, P =0.007; χ2=6.042, P =0.014 and χ2=7.662， P =0.006). Univariate analysis showed that karyotype at high risk of chromosome was an unfavorable factor affecting patients' RFS and OS, while 2 cycles of induction chemotherapy achieved CR, MRD- after the first induction chemotherapy and MRD- after the second induction chemotherapy was a protective factor affecting patients' RFS and OS. MRD- during consolidation therapy and MRD- at all three time points were all protective factors affecting patients' RFS, OS and CIR. Multivariate analysis showed that induction chemotherapy for 2 cycles achieved CR was a protective factor affecting patients' RFS and CIR, and MRD- during consolidation therapy was a protective factor affecting patients' RFS, OS and CIR. CONCLUSION: Early achievement of CR and MRD- in adult AML patients, especially MRD- during consolidation therapy, is a marker of good prognosis, and flow cytometry is the most commonly used method for MRD detection in AML patients.

Recent research progress in tetrodotoxin detection and quantitative analysis methods.

Tetrodotoxin (TTX) is a highly potent and widely distributed ion-channel marine neurotoxin; it has no specific antidote and poses a great risk to human health. Therefore, detecting and quantifying TTX to effectively implement prevention strategies is important for food safety. The development of novel and highly sensitive, highly specific, rapid, and simple techniques for trace TTX detection has attracted widespread attention. This review summarizes the latest advances in the detection and quantitative analysis of TTX, covering detection methods based on biological and cellular sensors, immunoassays and immunosensors, aptamers, and liquid chromatography-mass spectrometry. It further discusses the advantages and applications of various detection technologies developed for TTX and focuses on the frontier areas and development directions of TTX detection, providing relevant information for further investigations.

A novel BN aromatic module modified near-infrared fluorescent probe for monitoring carbon monoxide-releasing molecule CORM-3 in living cells and animals.

Carbon monoxide (CO), a significant gas transmitter, plays a vital role in the intricate functioning of living systems and is intimately linked to a variety of physiological and pathological processes. To comprehensively investigate CO within biological system, researchers have widely adopted CORM-3, a compound capable of releasing CO, which serves as a surrogate for CO. It aids in elucidating the physiological and pathological effects of CO within living organisms and can be employed as a therapeutic drug molecule. Therefore, the pivotal role of CORM-3 necessitates the development of effective probes that can facilitate the visualization and tracking of CORM-3 in living systems. However, creating fluorescent probes for real-time imaging of CORM-3 in living species has proven to be a persisting challenge that arises from factors such as background interference, light scattering and photoactivation. Herein, the BNDN fluorescent probe, a brand-new near-infrared is proposed. Remarkably, the BNDN probe offers several noteworthy advantages, including a substantial Stokes shift (201 nm), heightened sensitivity, exceptional selectivity, and an exceedingly low CORM-3 detection limit (0.7 ppb). Furthermore, the underlying sensing mechanism has been meticulously examined, revealing a process that revives the fluorophore by reducing the complex Cu2+ to Cu+. This distinctive NIR fluorescence "turn-on" character, coupled with its larger Stokes shift, holds great promise for achieving high resolution imaging. Most impressively, this innovative probe has demonstrated its efficacy in detecting exogenous CORM-3 in living animal. It is important to underscore that these endeavors mark a rare instance of a near-infrared probes successfully detecting exogenous CORM-3 in vivo. These exceptional outcomes highlighted the potential of BNDN as a highly promising new tool for in vivo detection of CORM-3. Considering the impressive imaging capabilities demonstrated by BNDN presented in this study, we anticipate that this tool may offer a compelling avenue for shedding light on the roles of CO in future research endeavors.

Handgrip Strength and Low Muscle Strength Rate in Chinese Adults - China, 2020.

What is already known on this topic?: Handgrip strength (HS) serves as a diagnostic marker for low muscle strength rate (LMSR) and reflects the level of skeletal muscle. Over the past two decades, global data indicate a downward trend in HS across various countries. What is added by this report?: According to the latest national data, the mean HS among Chinese adults aged 20 years and older was recorded at 40.4 kg for males and 25.1 kg for females in 2020. A decline in HS was observed with increasing age, particularly among women. Additionally, lower HS values were reported in rural areas, whereas LMSR was more prevalent in these regions. What are the implications for public health practice?: The analysis of HS and LMSR among Chinese adults is essential for the development and implementation of targeted interventions aimed at improving HS prevalence rates. This analysis is highly significant for public health, contributing to increased public awareness of LMSR and the promotion of preventative measures.

Inverted Sandwich-Type e-LCR Aided by Lambda Exonuclease-RecJf Combination Enables Ultrasensitive Detection of Low-Frequency EGFR-L858R Mutation in NSCLC.

Highly sensitive detection of low-frequency EGFR-L858R mutation is particularly important in guiding targeted therapy of nonsmall-cell lung carcinoma (NSCLC). To this end, a ligase chain reaction (LCR)-based electrochemical biosensor (e-LCR) with an inverted sandwich-type architecture was provided by combining a cooperation of lambda exonuclease-RecJf exonuclease (λ-RecJf exo). In this work, by designing a knife-like DNA substrate (an overhang ssDNA part referred to the "knife arm") and introducing the λ-RecJf exo, the unreacted DNA probes in the LCR were specially degraded while only the ligated products were preserved, after which the ligated knife-like DNA products were hybridized with capture probes on the gold electrode surface through the "knife arms", forming the inverted sandwich-type DNA structure and bringing the methylene blue-label close to the electrode surface to engender the electrical signal. Finally, the sensitivity of the e-LCR could be improved by 3 orders of magnitude with the help of the λ-RecJf exo, and due to the mutation recognizing in the ligation site of the employed ligase, this method could detect EGFR-L858R mutation down to 0.01%, along with a linear range of 1 fM-10 pM and a limit detection of 0.8 fM. Further, the developed method could distinguish between L858R positive and negative mutations in cultured cell samples, tumor tissue samples, and plasma samples, whose accuracy was verified by the droplet digital PCR, holding a huge potential in liquid biopsy for precisely guiding individualized-treatment of NSCLC patients with advantages of high sensitivity, low cost, and adaptability to point-of-care testing.

LncRNA PITPNA-AS1 mediates the diagnostic potential of miR-129-5p in prostate cancer.

BACKGROUND: LncRNA has an effective value in many diseases, which has long been applied in the diagnosis, treatment and prognosis of prostate cancer. This study focused on lncRNA PITPNA-AS1, and its diagnostic potential in prostate cancer has been explored. METHODS: The expression of PITPNA-AS1 and miR-129-5p in prostate cancer serum and sample cells was determined by real-time quantitative polymerase chain reaction (RT-qPCR). The relationship between the expression of PITPNA-AS1 and clinicopathological parameters was considered. ROC curve prompted the diagnostic value of PITPNA-AS1. The effect of PITPNA-AS1 on prostate cancer cells was verified using vitro cells assay. Luciferase activity assay and RIP assay demonstrated the sponge relationship of PITPNA-AS1 to miR-129-5p. RESULTS: PITPNA-AS1 level was increased, while miR-129-5p was obviously decreased in prostate cancer. PITPNA-AS1 expression was associated with Gleason grade, lymph node metastasis and TNM stage in patients. The area under the curve (AUC) was 0.910, with high sensitivity and specificity. PITPNA-AS1 was elucidated to directly target miR-129-5p, whereas silencing PITPNA-AS1 negatively affected prostate cancer cell proliferation, migration and invasion. Intervention of miR-129-5p inhibitor reversed the effect of silencing PITPNA-AS1 on cells. CONCLUSIONS: PITPNA-AS1 was relatively highly expressed in prostate cancer and mediated the pathophysiological process of patients, which may serve as a diagnostic indicator. Silencing of the PITPNA-AS1 sponge miR-129-5p inhibited the biological function of the cells, indicating that PITPNA-AS1 may represent a novel therapeutic target for prostate cancer.

The application of organoids in colorectal diseases.

Intestinal organoids are a three-dimensional cell culture model derived from colon or pluripotent stem cells. Intestinal organoids constructed in vitro strongly mimic the colon epithelium in cell composition, tissue architecture, and specific functions, replicating the colon epithelium in an in vitro culture environment. As an emerging biomedical technology, organoid technology has unique advantages over traditional two-dimensional culture in preserving parental gene expression and mutation, cell function, and biological characteristics. It has shown great potential in the research and treatment of colorectal diseases. Organoid technology has been widely applied in research on colorectal topics, including intestinal tumors, inflammatory bowel disease, infectious diarrhea, and intestinal injury regeneration. This review focuses on the application of organoid technology in colorectal diseases, including the basic principles and preparation methods of organoids, and explores the pathogenesis of and personalized treatment plans for various colorectal diseases to provide a valuable reference for organoid technology development and application.

CRISPR technology in human diseases.

Gene editing is a growing gene engineering technique that allows accurate editing of a broad spectrum of gene-regulated diseases to achieve curative treatment and also has the potential to be used as an adjunct to the conventional treatment of diseases. Gene editing technology, mainly based on clustered regularly interspaced palindromic repeats (CRISPR)-CRISPR-associated protein systems, which is capable of generating genetic modifications in somatic cells, provides a promising new strategy for gene therapy for a wide range of human diseases. Currently, gene editing technology shows great application prospects in a variety of human diseases, not only in therapeutic potential but also in the construction of animal models of human diseases. This paper describes the application of gene editing technology in hematological diseases, solid tumors, immune disorders, ophthalmological diseases, and metabolic diseases; focuses on the therapeutic strategies of gene editing technology in sickle cell disease; provides an overview of the role of gene editing technology in the construction of animal models of human diseases; and discusses the limitations of gene editing technology in the treatment of diseases, which is intended to provide an important reference for the applications of gene editing technology in the human disease.

Design, synthesis and antitumor activity of a novel FGFR2-selective degrader to overcome resistance of the FGFR2V564F gatekeeper mutation based on a pan-FGFR inhibitor.

Aberrant activation of fibroblast growth factor receptors (FGFRs) contributes to the development and progression of multiple types of cancer. Although many FGFR inhibitors have been approved by the FDA, their long-term therapeutic efficacy is hampered by acquired resistance to gatekeeper mutations and low subtype selectivity. FGFR2 has been found to be frequently amplified or mutated in many tumors. In this study, we designed several PROTACs with different E3 ligands based on LY2874455. By screening the length of the linker and the binding site in various degraders, we obtained a novel and highly efficient FGFR2-selective degrader 28e (DC50 = 0.645 nM, DCmax = 86 %). Compound 28e selectively degraded FGFR2 and essentially avoided degradation of FGFR1,3,4 isoforms (DC50 > 300 nM). Compound 28e significantly inhibited the proliferation of FGFR2-overexpressing cell lines, including KATOIII, SNU16, and AN3CA (IC50 = 0.794 nM/0.207 nM/4.626 nM), comparable to parental inhibitors. At the same time, the preferred compound showed superiority over the parental inhibitor in kinase inhibitory activity against the gatekeeper mutant isoform FGFR2V564F (IC50 = 0.121 nM). In summary, we identified 28e as a novel selective degrader of FGFR2 with high potency and high potential to overcome resistance to gatekeeper mutation. The discovery of 28e provides new evidence for the strategy of pan-inhibitor-based development of selective degrading agents.

Ocular biometric characteristics of Han ethnicity in Tianjin and Uyghur ethnicity in Xinjiang undergoing cataract surgery.

AIM: To analyze and compare the differences among ocular biometric parameters in Han and Uyghur populations undergoing cataract surgery. METHODS: In this hospital-based prospective study, 410 patients undergoing cataract surgery (226 Han patients in Tianjin and 184 Uyghur patients in Xinjiang) were enrolled. The differences in axial length (AL), anterior chamber depth (ACD), keratometry [steep K (Ks) and flat K (Kf)], and corneal astigmatism (CA) measured using IOL Master 700 were compared between Han and Uyghur patients. RESULTS: The average age of Han patients was higher than that of Uyghur patients (70.22±8.54 vs 63.04±9.56y, P<0.001). After adjusting for age factors, Han patients had longer AL (23.51±1.05 vs 22.86±0.92 mm, P<0.001), deeper ACD (3.06±0.44 vs 2.97±0.37 mm, P=0.001), greater Kf (43.95±1.40 vs 43.42±1.69 D, P=0.001), steeper Ks (45.00±1.47 vs 44.26±1.71 D, P=0.001), and higher CA (1.04±0.68 vs 0.79±0.65, P=0.025) than Uyghur patients. Intra-ethnic male patients had longer AL, deeper ACD, and lower keratometry than female patients; however, CA between the sexes was almost similar. In the correlation analysis, we observed a positive correlation between AL and ACD in patients of both ethnicities (rHan =0.48, rUyghur =0.44, P<0.001), while AL was negatively correlated with Kf (rHan =-0.42, rUyghur =-0.64, P<0.001) and Ks (rHan =-0.38, rUyghur =-0.66, P<0.001). Additionally, Kf was positively correlated with Ks (rHan =0.89, rUyghur =0.93, P<0.001). CONCLUSION: There are differences in ocular biometric parameters between individuals of Han ethnicity in Tianjin and those of Uyghur ethnicity in Xinjiang undergoing cataract surgery. These ethnic variances can enhance our understanding of ocular diseases related to these parameters and provide guidance for surgical procedures.

CBP60b clade proteins are prototypical transcription factors mediating immunity.

Transcriptional reprogramming is critical for plant immunity. Several calmodulin (CaM)-binding protein 60 (CBP60) family transcription factors (TFs) in Arabidopsis (Arabidopsis thaliana), including CBP60g, systemic acquired resistance deficient 1 (SARD1), CBP60a, and CBP60b, are critical for and show distinct roles in immunity. However, there are additional CBP60 members whose function is unclear. We report here that Arabidopsis CBP60c-f, 4 uncharacterized CBP60 members, play redundant roles with CBP60b in the transcriptional regulation of immunity responses, whose pCBP60b-driven expression compensates the loss of CBP60b. By contrast, neither CBP60g nor SARD1 is interchangeable with CBP60b, suggesting clade-specific functionalization. We further show that the function of CBP60b clade TFs relies on DNA-binding domains (DBDs) and CaM-binding domains, suggesting that they are downstream components of calcium signaling. Importantly, we demonstrate that CBP60s encoded in earliest land plant lineage Physcomitrium patens and Selaginella moellendorffii are functionally homologous to Arabidopsis CBP60b, suggesting that the CBP60b clade contains the prototype TFs of the CBP60 family. Furthermore, tomato and cucumber CBP60b-like genes rescue the defects of Arabidopsis cbp60b and activate the expression of tomato and cucumber SALICYLIC ACID INDUCTION DEFICIIENT2 (SID2) and ENHANCED DISEASE SUSCEPTIBILITY 1 (EDS1) genes, suggesting that immune response pathways centered on CBP60b are also evolutionarily conserved. Together, these findings suggest that CBP60b clade TFs are functionally conserved in evolution and positively mediate immunity.

Arabidopsis Sar1b is critical for pollen tube growth.

Pollen tube growth is an essential step leading to reproductive success in flowering plants, in which vesicular trafficking plays a key role. Vesicular trafficking from endoplasmic reticulum to the Golgi apparatus is mediated by the coat protein complex II (COPII). A key component of COPII is small GTPase Sar1. Five Sar1 isoforms are encoded in the Arabidopsis genome and they show distinct while redundant roles in various cellular and developmental processes, especially in reproduction. Arabidopsis Sar1b is essential for sporophytic control of pollen development while Sar1b and Sar1c are critical for gametophytic control of pollen development. Because functional loss of Sar1b and Sar1c resulted in pollen abortion, whether they influence pollen tube growth was unclear. Here we demonstrate that Sar1b mediates pollen tube growth, in addition to its role in pollen development. Although functional loss of Sar1b does not affect pollen germination, it causes a significant reduction in male transmission and of pollen tube penetration of style. We further show that membrane dynamics at the apex of pollen tubes are compromised by Sar1b loss-of-function. Results presented provide further support of functional complexity of the Sar1 isoforms.

Discovery of a first-in-class degrader for the protein arginine methyltransferase 6 (PRMT6).

PRMT6 is a member of the protein arginine methyltransferase family, which participates in a variety of physical processes and plays an important role in the occurrence and development of tumors. Using small molecules to design and synthesize targeted protein degraders is a new strategy for drug development. Here, we report the first-in-class degrader SKLB-0124 for PRMT6 based on the hydrophobic tagging (HyT) method.Importantly, SKLB-0124 induced proteasome dependent degradation of PRMT6 and significantly inhibited the proliferation of HCC827 and MDA-MB-435 cells. Moreover, SKLB-0124 effectively induced apoptosis and cell cycle arrest in these two cell lines. Our data clarified that SKLB-0124 is a promising selective PRMT6 degrader for cancer therapy which is worthy of further evaluation.

Efficacy of a mouthwash containing ε-poly-L-lysine, funme peptides and domiphen in reducing halitosis and supragingival plaque: a randomized clinical trial.

OBJECTIVE: To evaluate the antibacterial effectiveness of a combination of ε-poly-L-lysine (ε-PL), funme peptide (FP) as well as domiphen against oral pathogens, and assess the efficacy of a BOP® mouthwash supplemented with this combination in reducing halitosis and supragingival plaque in a clinical trial. MATERIALS AND METHODS: The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the compound against Fusobacterium nucleatum, Porphyromonas gingivalis, Streptococcus mutans, and Aggregatibacter actinomycetemcomitans were determined by the gradient dilution method. Subsequently, the CCK-8 assay was used to detect the toxicity of mouthwash on human gingival fibroblastst, and the effectiveness in reducing halitosis and supragingival plaque of the mouthwash supplemented with the combination was analyzed by a randomized, double-blind, parallel-controlled clinical trial. RESULTS: The combination exhibited significant inhibitory effects on tested oral pathogens with the MIC < 1.56% (v/v) and the MBC < 3.13% (v/v), and the mouthwash containing this combination did not inhibit the viability of human gingival fibroblasts at the test concentrations. The clinical trial showed that the test group displayed notably lower volatile sulfur compounds (VSCs) at 0, 10, 24 h, and 7 d post-mouthwash (P < 0.05), compared with the baseline. After 7 days, the VSC levels of the and control groups were reduced by 50.27% and 32.12%, respectively, and notably cutting severe halitosis by 57.03% in the test group. Additionally, the Plaque Index (PLI) of the test and control group decreased by 54.55% and 8.38%, respectively, and there was a significant difference in PLI between the two groups after 7 days (P < 0.01). CONCLUSIONS: The combination of ε-PL, FP and domiphen demonstrated potent inhibitory and bactericidal effects against the tested oral pathogens, and the newly formulated mouthwash added with the combination exhibited anti-dental plaque and anti-halitosis properties in a clinical trial and was safe. TRIAL REGISTRATION: The randomized controlled clinical trial was registered on Chinese Clinical Trial Registry (No. ChiCTR2300073816, Date: 21/07/2023).

Deep learning for high-resolution seismic imaging.

Seismic imaging techniques play a crucial role in interpreting subsurface geological structures by analyzing the propagation and reflection of seismic waves. However, traditional methods face challenges in achieving high resolution due to theoretical constraints and computational costs. Leveraging recent advancements in deep learning, this study introduces a neural network framework that integrates Transformer and Convolutional Neural Network (CNN) architectures, enhanced through Adaptive Spatial Feature Fusion (ASFF), to achieve high-resolution seismic imaging. Our approach directly maps seismic data to reflection models, eliminating the need for post-processing low-resolution results. Through extensive numerical experiments, we demonstrate the outstanding ability of this method to accurately infer subsurface structures. Evaluation metrics including Root Mean Square Error (RMSE), Correlation Coefficient (CC), and Structural Similarity Index (SSIM) emphasize the model's capacity to faithfully reconstruct subsurface features. Furthermore, noise injection experiments showcase the reliability of this efficient seismic imaging method, further underscoring the potential of deep learning in seismic imaging.

Research on a Method for Identification of Peanut Pests and Diseases Based on a Lightweight LSCDNet Model.

Timely and accurate identification of peanut pests and diseases, coupled with effective countermeasures, is pivotal for ensuring high-quality and efficient peanut production. Despite the prevalence of pests and diseases in peanut cultivation, challenges such as minute disease spots, the elusive nature of pests, and intricate environmental conditions often lead to diminished identification accuracy and efficiency. Moreover, continuous monitoring of peanut health in real-world agricultural settings demands solutions that are computationally efficient. Traditional deep learning models often require substantial computational resources, limiting their practical applicability. In response to these challenges, we introduce LSCDNet (Lightweight Sandglass and Coordinate Attention Network), a streamlined model derived from DenseNet. LSCDNet preserves only the transition layers to reduce feature map dimensionality, simplifying the model's complexity. The inclusion of a sandglass block bolsters features extraction capabilities, mitigating potential information loss due to dimensionality reduction. Additionally, the incorporation of coordinate attention addresses issues related to positional information loss during feature extraction. Experimental results showcase that LSCDNet achieved impressive metrics with accuracy, precision, recall, and Fl score of 96.67, 98.05, 95.56, and 96.79%, respectively, while maintaining a compact parameter count of merely 0.59 million. When compared with established models such as MobileNetV1, MobileNetV2, NASNetMobile, DenseNet-121, InceptionV3, and X-ception, LSCDNet outperformed with accuracy gains of 2.65, 4.87, 8.71, 5.04, 6.32, and 8.2%, respectively, accompanied by substantially fewer parameters. Lastly, we deployed the LSCDNet model on Raspberry Pi for practical testing and application and achieved an average recognition accuracy of 85.36%, thereby meeting real-world operational requirements.