Pinning Synchronization for Stochastic Complex Networks With Randomly Occurring Nonlinearities: Tackling Bit Rate Constraints and Allocations.

In this article, the ultimately bounded synchronization problem is investigated for a class of discrete-time stochastic complex networks under the pinning control strategy. Communication between system nodes and the remote controller is facilitated via wireless networks subject to bit rate constraints. The system model is distinguished by the inclusion of randomly occurring nonlinearities. A coding-decoding transmission mechanism under constrained bit rates is introduced to characterize the digital transmission process. To achieve synchronization of the network nodes with the unforced target node, a pinning controller is specifically devised based on the information from partially selected nodes. Through the application of the stochastic analysis method, a sufficient condition is derived for ensuring the mean-square boundedness of the synchronization error system. In addition, an optimization algorithm is introduced to address bit rate allocation and the design of desired controller gains. Within the presented theoretical framework, the correlation between the mean-square synchronization performance and bit rate allocation is further elucidated. To conclude, a simulation example is provided to substantiate the efficacy of the recommended pinning control approach.

The Masquelet technique triggers the formation of a network involving LncRNA, circRNA, miRNA, and mRNA during bone repair.

BACKGROUND: The ceRNA network, which is competitive endogenous RNA, uncovers a fresh mechanism of RNA interaction and holds significant importance in diverse biological processes. The aim of this study is to investigate the molecular process of induced membrane (IM) formation in bone defects using the Masquelet's induced membrane technique (MIMT), in order to offer novel insights and a theoretical foundation for enhancing the treatment of bone defects with MIMT. METHODS: In this work, we identified differentially expressed mRNAs (DEGs), lncRNAs (DELs), circRNAs (DECs), and miRNAs (DEMs). To explore the primary functions of the shared DEGs, we utilized Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Next, predictions were made for lncRNA-miRNA and miRNA-mRNA interactions, and the Cytoscape software was utilized to construct the regulatory network for ceRNA. RESULTS: By integrating GO and KEGG enrichment analysis, a total of 385 differentially expressed genes (DEGs) were discovered in the samples from the MIMT-treated group. Additionally, after re-annotating the probes and intersecting two sets of differently expressed miRNAs, 1304 differentially expressed lncRNAs (DELs) and 23 differentially expressed circRNAs (DECs) were identified. Furthermore, 13 differentially expressed miRNAs (DEMs) were obtained. Moreover, utilizing the anticipated objectives of DEMs, we acquired 1203 pairs of lncRNA-miRNA-mRNA interactors (comprising 24 lncRNAs, 10 miRNAs, and 115 mRNAs) and 250 pairs of circRNA-miRNA-mRNA interactions (comprising 7 circRNAs, 9 miRNAs, and 115 mRNAs). CEBPA, DGAT2, CDKN1A, PLIN2, and CIDEC were identified as the five hub proteins in the PPI network. LncRNA/circRNA-hsa-miR-671-5p could potentially regulate the primary central protein, CEBPA. CONCLUSIONS: In this study, we described the potential regulatory mechanism of the MIMT in treating bone defects. We proposed a new lncRNA-miRNA-mRNA ceRNA network that could help further explore the molecular mechanisms of bone repair.

Eimeria tenella rhoptry neck protein 2 plays a key role in the process of invading the host intestinal epithelium.

The Apicomplexa parasitic phylum rhoptry neck protein 2 (RON2) plays a key role in the process of invading host cells. Eimeria tenella, an intracellular protozoan shares a similar conserved invasion pattern. However, whether E. tenella RON2 participates in the process of invading the host intestinal epithelium is poorly understood. In this study, the sequence of EtRON2 was analyzed and expressed. The expression of the truncated extracellular N-terminal fragment of EtRON2 (403-700 aa, designated EtRON2403-700) with a molecular mass of 38.3 kDa. EtRON2 in the sporozoite protein was detected at 151.4 kDa by rabbit anti-rEtRON2403-700 antibody. Immunofluorescence results showed that EtRON2 was mainly localized to the nucleus and apex of the E. tenella sporozoite. qPCR results showed that the highest expression level of EtRON2 was detected in sporulated oocysts compared with other developmental stages of E. tenella. In vitro invasion inhibition assays showed that the capacity of sporozoites to invade DF-1 cells was significantly inhibited after pretreatment with the rabbit anti-rEtRON2403-700 antibody. Silencing the EtRON2 gene by RNA interference (RNAi) significantly inhibited EtRON2 expression and significantly reduced the invasion of DF-1 cells by sporozoites. In vivo experiments revealed a significant decrease parasite burden and oocyst outputs in chicks after infection with EtRON2 gene-silenced sporozoites by cloacal inoculation. Recombinant EtRON2403-700 (rEtRON2403-700) immunizes chicks effectively against E. tenella infection by inducing humoral immunity and upregulating IFN-γ and CD8+ T lymphocytes. Furthermore, chicks exhibited increased relative weight gain rates, lower cecum lesion scores, and reduced oocyst outputs during the E. tenella challenge. H&E staining showed that the cecum tissue of chicks immunized with rEtRON2403-700 showed relatively mild histopathological changes. In conclusion, the results of this study demonstrated that EtRON2 plays a key role in E. tenella invasion of the host intestinal epithelium and provides a potential target for vaccines against E. tenella infection.

Primary Amine-Functionalized Chiral Covalent Organic Framework Enables High-Efficiency Asymmetric Catalysis in Water.

Aqueous asymmetric catalysis using chiral covalent organic frameworks (COFs) represents a significant advancement but remains to be explored. Herein, we present the first example of aqueous asymmetric catalysis catalyzed by a primary amine-tagged chiral D-ADP-TAPB COF. The D-ADP-TAPB COF was synthesized by the postsynthetic deprotection of D-ADP-TAPB-Boc bearing a protective tert-butoxycarbonyl (Boc) group, which was constructed by a Schiff-base reaction between an alanine-derived chiral building block (D-ADP-Boc) and 1,3,5-tris(4-aminophenyl)benzene (TAPB). The crystalline D-ADP-TAPB COF exhibits a uniform, spherical morphology with abundant, well-distributed chiral primary amines, rendering it highly active in the asymmetric aldol reaction between cyclohexanone and 4-nitrobenzaldehyde. Notably, this reaction is conducted entirely in water, achieving impressive yields and enantiomeric excess (ee) values of up to 90 and 85%, respectively. To the best of our knowledge, D-ADP-TAPB COF represents the first chiral COF catalyst with high reactivity and enantioselectivity for an asymmetric aldol reaction solely in water, eliminating the need for conventional organic solvents. Moreover, a plausible mechanism for D-ADP-TAPB COF-mediated aqueous asymmetric aldol reactions is elucidated. This work not only expands the toolbox for designing rare primary amine-functionalized chiral COFs for asymmetric catalysis but also opens exciting avenues for developing green and water-based enantioselective catalysis.

The latest developments in the design and discovery of non-nucleoside reverse transcriptase inhibitors (NNRTIs) for the treatment of HIV.

INTRODUCTION: This review encapsulates the recent strides in the development of non-nucleoside reverse transcriptase inhibitors (NNRTIs) for HIV treatment, focusing on the novel structural designs that promise to overcome limitations of existing therapies, such as drug resistance and toxicity. AREAS COVERED: We underscore the application of computational chemistry and structure-based drug design in refining NNRTIs with enhanced potency and safety. EXPERT OPINION: Highlighting the emergence of diverse chemical scaffolds like diarylpyrimidines, indoles, DABOs and HEPTs, the review reveals compounds with nanomolar efficacy and improved pharmacokinetics. The integration of artificial intelligence in drug discovery is poised to accelerate the evolution of NNRTIs, laying the foundation for addressing drug resistance in the era of anti-HIV therapy through innovative designs and multi-target strategies.

Miniaturized Modular Click Chemistry-enabled Rapid Discovery of Unique SARS-CoV-2 Mpro Inhibitors With Robust Potency and Drug-like Profile.

The COVID-19 pandemic has required an expeditious advancement of innovative antiviral drugs. In this study, focused compound libraries are synthesized in 96- well plates utilizing modular click chemistry to rapidly discover potent inhibitors targeting the main protease (Mpro) of SARS-CoV-2. Subsequent direct biological screening identifies novel 1,2,3-triazole derivatives as robust Mpro inhibitors with high anti-SARS-CoV-2 activity. Notably, C5N17B demonstrates sub-micromolar Mpro inhibitory potency (IC50 = 0.12 µM) and excellent antiviral activity in Calu-3 cells determined in an immunofluorescence-based antiviral assay (EC50 = 0.078 µM, no cytotoxicity: CC50 > 100 µM). C5N17B shows superior potency to nirmatrelvir (EC50 = 1.95 µM) and similar efficacy to ensitrelvir (EC50 = 0.11 µM). Importantly, this compound displays high antiviral activities against several SARS-CoV-2 variants (Gamma, Delta, and Omicron, EC50 = 0.13 - 0.26 µM) and HCoV-OC43, indicating its broad-spectrum antiviral activity. It is worthy that C5N17B retains antiviral activity against nirmatrelvir-resistant strains with T21I/E166V and L50F/E166V mutations in Mpro (EC50 = 0.26 and 0.15 µM, respectively). Furthermore, C5N17B displays favorable pharmacokinetic properties. Crystallography studies reveal a unique, non-covalent multi-site binding mode. In conclusion, these findings substantiate the potential of C5N17B as an up-and-coming drug candidate targeting SARS-CoV-2 Mpro for clinical therapy.

A new treatment approach of toripalimab in combination with concurrent platinum-based chemoradiotherapy for locally advanced cervical cancer: A phase II clinical trial.

This study investigated the efficacy and safety of toripalimab in combination with concurrent platinum-based chemoradiation in patients with untreated locally advanced cervical cancer. Eligible patients received toripalimab 240 mg once every 3 weeks in combination with concurrent platinum-based chemoradiotherapy, followed by the maintenance of toripalimab once every 6 weeks up to 1 year. The primary endpoint was objective response rate (ORR). Secondary endpoints included 2-year and 3-year progression-free survival (PFS) rates, 3-year overall survival (OS) rate, and safety. Biomarker analysis of PD-L1 expression and genomic mutational analysis by next-generation sequencing were conducted, as well as PD-L1 expression on tumor biopsies. A total of 82 patients were enrolled. The median follow-up was 21 months (range, 5.2-44.5 months). The ORR and disease control rate were both 87.8% among the 82 patients. Median PFS and OS were not reached. A trend toward longer PFS was observed in the populations with a PD-L1 combined positive score ≥10, low tumor mutation burden and loss of heterozygosity in human leukocyte antigen (HLA LOH) detected populations. A total of 37 patients experienced treatment-related adverse events, of which 17 (20.7%) patients experienced grade 3 or higher adverse events. Collectively, toripalimab plus concurrent platinum-based chemoradiotherapy showed promising antitumor efficacy with acceptable safety profiles in patients with untreated locally advanced cervical cancer.

Nonfragile Impulsive State Estimation for Complex Networks With Markovian Switching Topologies Subject to Limited Bit Rate Constraints.

In this article, we consider the impulsive estimation problem for a specific category of discrete-time complex networks (CNs) characterized by Markovian switching topologies. The measurement outputs of the underlying CNs, transmitted to the observer over wireless networks, are subject to bit rate constraints. To effectively reduce the estimation error and enhance estimation performance, a mode-dependent impulsive observer is proposed that employs the impulse mechanism. The application of stochastic analysis techniques leads to the derivation of a sufficient condition for ensuring the mean-square boundedness of the estimation error dynamics. The upper bound of the error is then analyzed by iteratively exploring the Lyapunov relation at both impulsive and non-impulsive instants. Moreover, an optimization algorithm is presented for handling the bit rate allocation, which is coupled with the design of desired observer gains using the linear matrix inequality (LMI) approach. Within this theoretical framework, the relationship between the mean-square estimation performance and the bit rate allocation protocol is further elucidated. Finally, a simulation example is provided to demonstrate the validity and effectiveness of the proposed impulsive estimation approach.

Constraint-Induced Movement Therapy (CIMT) and Neural Precursor Cell (NPC) Transplantation Synergistically Promote Anatomical and Functional Recovery in a Hypoxic-Ischemic Mouse Model.

Cerebral palsy (CP) is a common neurodevelopmental disorder characterized by pronounced motor dysfunction and resulting in physical disability. Neural precursor cells (NPCs) have shown therapeutic promise in mouse models of hypoxic-ischemic (HI) perinatal brain injury, which mirror hemiplegic CP. Constraint-induced movement therapy (CIMT) enhances the functional use of the impaired limb and has emerged as a beneficial intervention for hemiplegic CP. However, the precise mechanisms and optimal application of CIMT remain poorly understood. The potential synergy between a regenerative approach using NPCs and a rehabilitation strategy using CIMT has not been explored. We employed the Rice-Vannucci HI model on C57Bl/6 mice at postnatal day (PND) 7, effectively replicating the clinical and neuroanatomical characteristics of hemiplegic CP. NPCs were transplanted in the corpus callosum (CC) at PND21, which is the age corresponding to a 2-year-old child from a developmental perspective and until which CP is often not formally diagnosed, followed or not by Botulinum toxin injections in the unaffected forelimb muscles at PND23, 26, 29 and 32 to apply CIMT. Both interventions led to enhanced CC myelination and significant functional recovery (as shown by rearing and gait analysis testing), through the recruitment of endogenous oligodendrocytes. The combinatorial treatment indicated a synergistic effect, as shown by newly recruited oligodendrocytes and functional recovery. This work demonstrates the mechanistic effects of CIMT and NPC transplantation and advocates for their combined therapeutic potential in addressing hemiplegic CP.

Preparation and Molecular Dynamic Simulation of Superfine CL-20/TNT Cocrystal Based on the Opposite Spray Method.

In view of the current problems of slow crystallization rate, varying grain sizes, complex process conditions, and low safety in the preparation of CL-20/TNT cocrystal explosives in the laboratory, an opposite spray crystallization method is provided to quickly prepare ultrafine explosive cocrystal particles. CL-20/TNT cocrystal explosive was prepared using this method, and the obtained cocrystal samples were characterized by electron microscopy morphology, differential thermal analysis, infrared spectroscopy, and X-ray diffraction analysis. The effects of spray temperature, feed ratio, and preparation method on the formation of explosive cocrystal were studied, and the process conditions of the pneumatic atomization spray crystallization method were optimized. The crystal plane binding energy and molecular interaction forces between CL-20 and TNT were obtained through molecular dynamic simulation, and the optimal binding crystal plane and cocrystal mechanism were analyzed. The theoretical calculation temperature of the binding energy was preliminarily explored in relation to the preparation process temperature of cocrystal explosives. The mechanical sensitivity of ultrafine CL-20/TNT cocrystal samples was tested. The results showed that choosing acetone as the cosolvent, a spraying temperature of 30 °C, and a feeding ratio of 1:1 was beneficial for the formation and growth of cocrystal. The prepared CL-20/TNT cocrystal has a particle size of approximately 10 µm. The grain size is small, and the crystallization rate is fast. The impact and friction sensitivity of ultrafine CL-20/TNT cocrystal samples were significantly reduced. The experimental process conditions are simple and easy to control, and the safety of the preparation process is high, providing certain technical support for the preparation of high-quality cocrystal explosives.

Luteolin protects against myocardial ischemia/reperfusion injury by reducing oxidative stress and apoptosis through the p53 pathway.

OBJECTIVE: Myocardial ischemia/reperfusion injury (MIRI) is an obstacle to the success of cardiac reperfusion therapy. This study explores whether luteolin can mitigate MIRI by regulating the p53 signaling pathway. METHODS: Model mice were subjected to a temporary surgical ligation of the left anterior descending coronary artery, and administered luteolin. The myocardial infarct size, myocardial enzyme levels, and cardiac function were measured. Latent targets and signaling pathways were screened using network pharmacology and molecular docking. Then, proteins related to the p53 signaling pathway, apoptosis and oxidative stress were measured. Hypoxia/reoxygenation (HR)-incubated HL1 cells were used to validate the effects of luteolin in vitro. In addition, a p53 agonist and an inhibitor were used to investigate the mechanism. RESULTS: Luteolin reduced the myocardial infarcted size and myocardial enzymes, and restored cardiac function in MIRI mice. Network pharmacology identified p53 as a hub target. The bioinformatic analyses showed that luteolin had anti-apoptotic and anti-oxidative properties. Additionally, luteolin halted the activation of p53, and prevented both apoptosis and oxidative stress in myocardial tissue in vivo. Furthermore, luteolin inhibited cell apoptosis, JC-1 monomer formation, and reactive oxygen species elevation in HR-incubated HL1 cells in vitro. Finally, the p53 agonist NSC319726 downregulated the protective attributes of luteolin in the MIRI mouse model, and both luteolin and the p53 inhibitor pifithrin-α demonstrated a similar therapeutic effect in the MIRI mice. CONCLUSION: Luteolin effectively treats MIRI and may ameliorate myocardial damage by regulating apoptosis and oxidative stress through its targeting of the p53 signaling pathway. Please cite this article as: Zhai P, Ouyang XH, Yang ML, Lin L, Li JY, Li YM, Cheng X, Zhu R, Hu DS. Luteolin protects against myocardial ischemia/reperfusion injury by reducing oxidative stress and apoptosis through the p53 pathway. J Integr Med. 2024; Epub ahead of print.Please cite this article as: Zhai P, Ouyang XH, Yang ML, Lin L, Li JY, Li YM, Cheng X, Zhu R, Hu DS. Luteolin protects against myocardial ischemia/reperfusion injury by reducing oxidative stress and apoptosis through the p53 pathway. J Integr Med. 2024; Epub ahead of print.

Brachial plexopathy following stereotactic body radiation therapy in apical lung malignancies: A dosimetric pooled analysis of individual patient data.

BACKGROUND AND OBJECTIVES: The aim of this study is to establish dosimetric constraints for the brachial plexus at risk of developing grade ≥ 2 brachial plexopathy in the context of stereotactic body radiation therapy (SBRT). PATIENTS AND METHODS: Individual patient data from 349 patients with 356 apical lung malignancies who underwent SBRT were extracted from 5 articles. The anatomical brachial plexus was delineated following the guidelines provided in the atlases developed by Hall, et al. and Kong, et al.. Patient characteristics, pertinent SBRT dosimetric parameters, and brachial plexopathy grades (according to CTCAE 4.0 or 5.0) were obtained. Normal tissue complication probability (NTCP) models were used to estimate the risk of developing grade ≥ 2 brachial plexopathy through maximum likelihood parameter fitting. RESULTS: The prescription dose/fractionation schedules for SBRT ranged from 27 to 60 Gy in 1 to 8 fractions. During a follow-up period spanning from 6 to 113 months, 22 patients (6.3 %) developed grade ≥2 brachial plexopathy (4.3 % grade 2, 2.0 % grade 3); the median time to symptoms onset after SBRT was 8 months (ranged, 3-54 months). NTCP models estimated a 10 % risk of grade ≥2 brachial plexopathy with an anatomic brachial plexus maximum dose (Dmax) of 20.7 Gy, 34.2 Gy, and 42.7 Gy in one, three, and five fractions, respectively. Similarly, the NTCP model estimates the risks of grade ≥2 brachial plexopathy as 10 % for BED Dmax at 192.3 Gy and EQD2 Dmax at 115.4 Gy with an α/ß ratio of 3, respectively. Symptom persisted after treatment in nearly half of patients diagnosed with grade ≥2 brachial plexopathy (11/22, 50 %). CONCLUSIONS: This study establishes dosimetric constraints ranging from 20.7 to 42.7 Gy across 1-5 fractions, aimed at mitigating the risk of developing grade ≥2 brachial plexopathy following SBRT. These findings provide valuable guidance for future ablative SBRT in apical lung malignancies.

The relationship between openness to experience and humor production: Exploring the mediating roles of cognitive flexibility and ambiguity tolerance.

The purpose of this study was to examine how individual openness to experience influences humor production and to explore the underlying psychological mechanisms of this relationship, specifically focusing on cognitive flexibility (the cognitive path) and ambiguity tolerance (the motivational path). To comprehensively evaluate individuals' humor production ability, Study 1 employed a subjective self-report questionnaire on sense of humor, while Study 2 used an objective humor dialogue generation task. The results of Study 1 indicated that openness to experience did not directly impact sense of humor; instead, the relationship between openness to experience and sense of humor was fully mediated by cognitive flexibility. In Study 2, findings showed that openness to experience positively predicted humor production ability, with ambiguity tolerance partially mediating this effect. These results suggest that individuals with higher levels of openness to experience have a greater capacity for generating humorous perspectives. Moreover, the study identified two psychological pathways-cognition and motivation-in the process of generating funny ideas. The specific pathway influenced by the measurement method used for humor production further highlights the importance of both cognitive flexibility and ambiguity tolerance in understanding how openness to experience contributes to humor production.

The Differences in Parameters in Ultrasound Imaging and Biomechanical Properties of the Quadriceps Femoris with Unilateral Knee Osteoarthritis in the Elderly: A Preliminary Observational Study.

Purpose: Our study aims to evaluate differences in muscle parameters of the quadriceps muscles in patients with knee osteoarthritis (KOA) in older adults. Methods: The study included 40 patients diagnosed with unilateral knee osteoarthritis in the KOA group (KG) and 40 asymptomatic elderly individuals in the control group (CG). Muscle ultrasonic mean echo intensity and shear modulus, as well as tone and stiffness of the rectus femoris (RF), vastus medialis (VM), and vastus lateralis (VL) were analyzed. Additionally, clinical correlations were performed. Results: In the KG group, there were significant differences in echo intensity, shear modulus, and tone between the affected and unaffected sides for RF (p=0.003, 0.019, 0.014), while VM showed significant differences in shear modulus and tone (p=0.006, 0.002). Additionally, VL exhibited significant differences in echo intensity, shear modulus, and stiffness (p=0.007, 0.006, 0.010). Compared to the CG group, the KG group showed significant differences in echo intensity of the affected side RF (p=0.001). VM exhibited statistically significant differences in echo intensity and shear modulus (p < 0.001, p=0.008), while VL showed statistically significant differences in echo intensity, tone, and stiffness (p < 0.001, p=0.028, p < 0.001). The correlation results showed that patients with unilateral KOA, VM, and VL echo intensity were correlated with K-L grade (r = 0.443, p=0.004; r = 0.469, p=0.002). The tone of VL was correlated with VAS and WOMAC (r = 0.327, p=0.039; r = 0.344, p=0.030). Conclusion: The parameters of the quadriceps femoris muscle exhibit asymmetry between the affected and unaffected sides in patients with unilateral KOA, as well as a difference between the dominant side of healthy older individuals and the affected side of KOA.

TUBA1C orchestrates the immunosuppressive tumor microenvironment and resistance to immune checkpoint blockade in clear cell renal cell carcinoma.

Background: Clear cell renal cell carcinoma (ccRCC) poses substantial treatment challenges, especially in advanced stages where the efficacy of immune checkpoint blockade (ICB) therapy varies significantly. Elevated expression of the oncogene TUBA1C has been correlated with poor prognosis in various cancers, however, its role in ccRCC is unclear, especially concerning ICB resistance. Methods: Single-cell analysis was used to examine gene expression variations in malignant cells post-ICB therapy. This included investigating TUBA1C expression across different ICB response groups and its relationship with CD274. A general module of action was identified through pan-cancer and pan-tissue analysis. TUBA1C expression and its association with clinical characteristics and prognosis was further validated. Multiple algorithms were employed to explore immune cell infiltration levels, and the DepMap database was utilized to assess gene dependency and mutation status in kidney cancer cell lines. The in silico knockout of TUBA1C was performed using deep learning model, complemented by immunohistochemical assays, clinical cohort and functional assays validations. Results: TUBA1C expression is elevated in malignant cells following ICB therapy and is correlated with ICB resistance in ccRCC. High TUBA1C expression activates PI3K/AKT pathway and is associated with increased infiltration of regulatory T cells and myeloid-derived suppressor cells, which contributes to an immunosuppressive microenvironment in ccRCC. Patients with high TUBA1C expression exhibit a greater tumor mutation burden and increased genetic variation, which causes a worse prognosis. Additionally, TUBA1C dependency and its effects were evident in kidney cancer cell lines, where mutations conferred resistance to anti-PD-L1 therapy. In silico knockout analyses indicated that treatment targeting TUBA1C shifted malignant cells to a state responsive to ICB therapy. Immunohistochemistry, RT-qPCR and clinical cohort validation further confirmed that TUBA1C expression was upregulated and contributed to poorer outcome in ccRCC. Finaly, wound healing and CCK-8 assays demonstrated the potent oncogenic function of TUBA1C. Conclusions: TUBA1C is a pivotal regulator in ccRCC, affecting both disease progression and the effectiveness of ICB therapy by fostering an immunosuppressive microenvironment mediated by the PI3K/AKT pathway. Additionally, TUBA1C holds promise, both as a prognostic biomarker and a therapeutic target, for enhancing responsiveness to ICB.

The H/F substitution strategy can achieve large spontaneous polarization in 1D hybrid perovskite ferroelectrics.

Hybrid organic-inorganic perovskite (HOIP) ferroelectrics exhibit polarization reversibility and have a wide range of applications in the fields of smart switches, memorizers, sensors, etc. However, the inherent limitations of small spontaneous polarization (P s) and large coercive field (E c) in ferroelectrics have impeded their broader utilization in electronics and data storage. Molecular ferroelectrics, as a powerful supplement to inorganic ferroelectrics, have shown great potential in the new generation of flexible wearable electronic devices. The important research responsibility is to greatly improve progressiveness and overcome the above limitations. Here, a novel one-dimensional (1D) HOIP ferroelectric, (3-F-BTAB)PbBr3 (3-F-BTAB = 3-fluorobenzyltrimethylammonium), was successfully synthesized by employing the H/F substitution strategy to modify parent compound (BTAB)PbBr3 (BTAB = benzyltrimethylammonium), which undergoes a ferroelectric phase transition with Aizu notation 2/mF2 at 420 K. Notably, (3-F-BTAB)PbBr3 demonstrates exceptional ferroelectric properties with a large P s of 7.18 µC cm-2 and a low E c of 1.78 kV cm-1. As far as we know, (3-F-BTAB)PbBr3 features the largest P s among those reported for 1D lead-based HOIP ferroelectrics. This work enriches the 1D lead-based ferroelectric family and provides guidance for applying ferroelectrics in low-voltage polar memories.

AFSC: A self-supervised augmentation-free spatial clustering method based on contrastive learning for identifying spatial domains.

Recent research in spatial transcriptomics allows researchers to analyze gene expression without losing spatial information. Spatial information can assist in cell communication, identification of new cell subtypes, which provides important research methods for multiple fields such as microenvironment interactions and pathological processes of diseases. Identifying spatial domains is an important step in spatial transcriptomics analysis, and improving spatial clustering methods can benefit for identifying spatial domains. In addition to eliminating noise in original gene expression, how to use spatial information to assist clustering has also become a new problem. A variety of calculating methods have been applied to spatial clustering, including contrastive learning methods. However, existing spatial clustering methods based on contrastive learning use data augmentation to generate positive and negative pairs, which will inevitably destroy the biological meaning of the data. We propose a new self-supervised spatial clustering method based on contrastive learning, Augmentation-Free Spatial Clustering (AFSC), which integrates spatial information and gene expression to learn latent representations. We construct a contrastive learning module without negative pairs or data augmentation by designing Teacher and Student Encoder. We also design an unsupervised clustering module to make clustering and contrastive learning be trained together. Experiments on multiple spatial transcriptomics datasets at different resolutions demonstrate that our method performs well in self-supervised spatial clustering tasks. Furthermore, the learned representations can be used for various downstream tasks including visualization and trajectory inference.

Unveiling cold Code: Acinetobacter calcoaceticus TY1's adaptation strategies and applications in nitrogen treatment.

Overcoming low nitrogen removal efficiency at low temperatures is a challenge in biological treatment. This study investigated the cold-tolerant heterotrophic nitrification-aerobic denitrification by Acinetobacter calcoaceticus TY1. Transcriptomic and biochemical analyses indicated that strain TY1 upregulated genes for energy production, assimilation, cell motility, and antioxidant enzyme production under cold stress, maintaining functions such as energy supply, nitrogen utilization, and oxidative defense. Increasing the synthesis of extracellular polysaccharides, unsaturated fatty acids, and medium-chain fatty acids and secreting large amounts of antioxidant enzymes ensured cell membrane flexibility while enhancing the antioxidant system. Immobilization experiments showed that biofilms accelerated the removal of nitrogen pollutants and demonstrated good stability, with carriers being reusable to five times, maintaining high ammonia nitrogen (63.90 %) and total nitrogen (50.66 %) removal rates. These findings reveal the cold tolerance mechanisms of strain TY1 and its excellent practical potential as a candidate for wastewater treatment in cold regions.

Aloperine Suppresses Cancer Progression by Interacting with VPS4A to Inhibit Autophagosome-lysosome Fusion in NSCLC.

Aloperine (ALO), a quinolizidine-type alkaloid isolated from a natural Chinese herb, has shown promising antitumor effects. Nevertheless, its common mechanism of action and specific target remain elusive. Here, it is demonstrated that ALO inhibits the proliferation and migration of non-small cell lung cancer cell lines in vitro and the tumor development in several mouse tumor models in vivo. Mechanistically, ALO inhibits the fusion of autophagosomes with lysosomes and the autophagic flux, leading to the accumulation of sequestosome-1 (SQSTM1) and production of reactive oxygen species (ROS), thereby inducing tumor cell apoptosis and preventing tumor growth. Knockdown of SQSTM1 in cells inhibits ROS production and reverses ALO-induced cell apoptosis. Furthermore, VPS4A is identified as a direct target of ALO, and the amino acids F153 and D263 of VPS4A are confirmed as the binding sites for ALO. Knockout of VPS4A in H1299 cells demonstrates a similar biological effect as ALO treatment. Additionally, ALO enhances the efficacy of the anti-PD-L1/TGF-ß bispecific antibody in inhibiting LLC-derived subcutaneous tumor models. Thus, ALO is first identified as a novel late-stage autophagy inhibitor that triggers tumor cell death by targeting VPS4A.

Molecular characterization of cassava zinc finger-homeodomain (ZF-HD) transcription factors reveals their role in disease resistance.

The production of cassava (Manihot esculenta Crantz) is constantly threatened by cassava bacterial blight (CBB), caused by Xanthomonas phaseoli pv. manihotis (Xpm). Zinc finger-homeodomain (ZF-HD) belongs to a family of homozygous heterotypic cassette genes widely implicated in various developmental and physiological processes in plants. Despite their importance, a comprehensive analysis of ZF-HD genes, particularly those involved in disease resistance, has not been performed for cassava. In the present study, we utilized bioinformatics methods to identify 21 ZF-HD genes distributed across 11 chromosomes of cassava genome, with the majority exhibiting gene structure without introns. Phylogenetic analysis categorized these genes into two major groups (MIF and ZHD) with five subgroups. We observed fourteen pairs of duplicated genes, suggesting that segmental duplication has likely facilitated the expansion of the cassava ZF-HD gene family. Comparative orthologous analyses between cassava and other plant species shed light on the evolutionary trajectory of this gene family. Promoter analyses revealed multiple hormone- and stress-related elements, indicative of a functional role in stress responses. Expression profiling through RNA-seq and quantitative real-time PCR (qRT-PCR) demonstrated that certain cassava ZF-HD genes are up-regulated in response to Xpm infection, suggesting their involvement in defense mechanisms. Notably, MeZHD7 gene was identified via virus induced gene silencing (VIGS) as potentially crucial in conferring resistance against CBB. Results from subcellular localization experiments indicated that MeZHD7 was localized in the nucleus. The Luciferase reporter assay demonstrated an interaction between MeZHD7 and MeMIF5. These findings may lay the foundation for further cloning and functional analyses of cassava ZF-HD genes, particularly those associated with pathogen resistance.