The zinc finger protein DHHC09 S-acylates the kinase STRK1 to regulate H2O2 homeostasis and promote salt tolerance in rice.

Soil salinity results in oxidative stress and heavy losses to crop production. The S-acylated protein SALT TOLERANCE RECEPTOR-LIKE CYTOPLASMIC KINASE 1 (STRK1) phosphorylates and activates CATALASE C (CatC) to improve rice (Oryza sativa L.) salt tolerance, but the molecular mechanism underlying its S-acylation involved in salt signal transduction awaits elucidation. Here, we show that the DHHC-type zinc finger protein DHHC09 S-acylates STRK1 at Cys5, Cys10, and Cys14 and promotes salt and oxidative stress tolerance by enhancing rice H2O2-scavenging capacity. This modification determines STRK1 targeting to the plasma membrane or lipid nanodomains and is required for its function. DHHC09 promotes salt signaling from STRK1 to CatC via transphosphorylation, and its deficiency impairs salt signal transduction. Our findings demonstrate that DHHC09 S-acylates and anchors STRK1 to the plasma membrane to promote salt signaling from STRK1 to CatC, thereby regulating H2O2 homeostasis and improving salt stress tolerance in rice. Moreover, overexpression of DHHC09 in rice mitigates grain yield loss under salt stress. Together, these results shed light on the mechanism underlying the role of S-acylation in RLK/RLCK-mediated salt signal transduction and provide a strategy for breeding highly salt-tolerant rice.

Prolonged myelin deficits contribute to neuron loss and functional impairments after ischaemic stroke.

Ischaemic stroke causes neuron loss and long-term functional deficits. Unfortunately, effective approaches to preserving neurons and promoting functional recovery remain unavailable. Oligodendrocytes, the myelinating cells in the CNS, are susceptible to oxygen and nutrition deprivation and undergo degeneration after ischaemic stroke. Technically, new oligodendrocytes and myelin can be generated by the differentiation of oligodendrocyte precursor cells (OPCs). However, myelin dynamics and their functional significance after ischaemic stroke remain poorly understood. Here, we report numerous denuded axons accompanied by decreased neuron density in sections from ischaemic stroke lesions in human brain, suggesting that neuron loss correlates with myelin deficits in these lesions. To investigate the longitudinal changes in myelin dynamics after stroke, we labelled and traced pre-existing and newly-formed myelin, respectively, using cell-specific genetic approaches. Our results indicated massive oligodendrocyte death and myelin loss 2 weeks after stroke in the transient middle cerebral artery occlusion (tMCAO) mouse model. In contrast, myelin regeneration remained insufficient 4 and 8 weeks post-stroke. Notably, neuronal loss and functional impairments worsened in aged brains, and new myelin generation was diminished. To analyse the causal relationship between remyelination and neuron survival, we manipulated myelinogenesis by conditional deletion of Olig2 (a positive regulator) or muscarinic receptor 1 (M1R, a negative regulator) in OPCs. Deleting Olig2 inhibited remyelination, reducing neuron survival and functional recovery after tMCAO. Conversely, enhancing remyelination by M1R conditional knockout or treatment with the pro-myelination drug clemastine after tMCAO preserved white matter integrity and neuronal survival, accelerating functional recovery. Together, our findings demonstrate that enhancing myelinogenesis is a promising strategy to preserve neurons and promote functional recovery after ischaemic stroke.

Copper Single-Atom-Based Metal-Organic Framework for Ultrasound-Enhanced Nanocatalytic Therapy.

Chemodynamic therapy (CDT) is an emerging therapeutic modality triggered by endogenous substances in the tumor microenvironment (TME) to generate reactive oxygen species. However, the mild acid pH, low H2O2 concentration, and overexpressed glutathione can suppress the CDT efficiency. Herein, ultrasound (US)-triggered Cu2+-based single-atom nanoenzymes (FA-NH2-UiO-66-Cu, FNUC) are constructed with the performance of target and glutathione depletion. In the TME, the single-atom Cu sites of FNUC consume glutathione and the FNUC:Cu+ generates •OH via peroxidase-like activity. The US-activated FNUC exhibits a fast •OH generation rate, a low Michaelis constant, and a large •OH concentration, indicating the cavitation effect of US promotes the •OH generation. Meanwhile, the tumor target of FNUC is confirmed by NIR-II fluorescence imaging, in which it is modified with IR-1061. Combined with the antitumor performance of FNUC in vitro and in vivo, the novel Cu-based SAzymes can achieve efficient and precise cancer treatment.

Staphylococcus aureus Conquers Host by Hijacking Mitochondria via PFKFB3 in Epithelial Cells.

Staphylococcus aureus (S. aureus) persists within mammary epithelial cells for an extended duration, exploiting the host metabolic resources to facilitate replication. This study revealed a mechanism by which intracellular S. aureus reprograms host metabolism, with PFKFB3 playing a crucial role in this process. Mechanistically, S. aureus induced mitochondrial damage, leading to increased levels of mitochondrial reactive oxygen species (mROS) and dysfunction in electron transport chain (ETC). Moreover, S. aureus shifted the balance of mitochondrial dynamics from fusion to fission, subsequently activating PINK1-PRKN-dependent mitophagy, causing loss of the sirtuin 3 (SIRT3) to stabilize hypoxic inducible factor 1α (HIF1α), and shifting the host metabolism toward enhanced glycolysis. The inhibition of PFKFB3 reversed the mitochondrial damage and degradation of SIRT3 induced by S. aureus. Overall, our findings elucidate the mechanism by which S. aureus reprograms host metabolism and offer insights into the treatment of S. aureus infection.

TLR9 activation induces immunosuppression and tumorigenesis via PARP1/PD-L1 signaling pathway in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer, and metastasis and immunosuppression are responsible for the poor prognosis of OSCC. Previous studies have shown that poly(ADP-ribose) polymerase (PARP)1 plays a key role in the pathogenesis of OSCC. Therefore, PARP1 may serve as an important research target for the potential treatment of OSCC. Here, we aimed to investigate the role of PARP1 in the tumorigenesis of OSCC and elucidate the key molecular mechanisms of its upstream and downstream regulation in vivo and in vitro. In human OSCC tissues and cells, Toll-like receptor (TLR)9 and PD-L1 were highly expressed and PARP1 was lowly expressed. Suppression of TLR9 remarkably repressed CAL27 and SCC9 cell proliferation, migration, and invasion. After coculture, we found that low expression of TLR9 inhibited PD-L1 expression and immune escape. In addition, TLR9 regulated PD-L1 expression through the PARP1/STAT3 pathway. PARP1 mediated the effects of TLR9 on OSCC cell proliferation, migration, and invasion and immune escape. Additionally, in vivo experiments further verified that TLR9 promoted tumor growth and immune escape by inhibiting PARP1. Collectively, TLR9 activation induced immunosuppression and tumorigenesis via PARP1/PD-L1 signaling pathway in OSCC, providing important insights for subsequent in-depth exploration of the mechanism of OSCC.NEW & NOTEWORTHY In this research, we took PARP1 as the key target to explore its regulatory effect on oral squamous cell carcinoma (OSCC). The key molecular mechanisms involved in its upstream and downstream regulation were elucidated in OSCC cell lines in vitro and tumor-bearing mice in vivo, combined with clinical OSCC tissues.

Research progress of the netrins and their receptors in cancer.

Netrins, a family of secreted and membrane-associated proteins, can regulate axonal guidance, morphogenesis, angiogenesis, cell migration, cell survival, and tumorigenesis. Four secreted netrins (netrin 1, 3, 4 and 5) and two glycosylphosphatidylinositols-anchored membrane proteins, netrin-G1 and G2, have been identified in mammals. Netrins and their receptors can serve as a biomarker and molecular therapeutic target for pathological differentiation, diagnosis and prognosis of malignant cancers. We review here the potential roles of the netrins family and their receptors in cancer.

Soluble Nanographene C222: Synthesis and Applications for Synergistic Photodynamic/Photothermal Therapy.

Nanographene C222, which consists of a planar graphenic plane containing 222 carbon atoms, holds the record as the largest planar nanographene synthesized to date. However, its complete insolubility makes the processing of C222 difficult. Here we addressed this issue by introducing peripheral substituents perpendicular to the graphene plane, effectively disrupting the interlayer stacking and endowing C222 with good solubility. We also found that the electron-withdrawing substituents played a crucial role in the cyclodehydrogenation process, converting the dendritic polyphenylene precursor to C222. After disrupting the interlayer stacking, the introduction of only a few peripheral carboxylic groups allowed C222 to dissolve in phosphate buffer saline, reaching a concentration of up to 0.5 mg/mL. Taking advantage of the good photosensitizing and photothermal properties of the inner C222 core, the resulting water-soluble C222 emerged as a single-component agent for both photothermal and photodynamic tumor therapy, exhibiting an impressive tumor inhibition rate of 96%.

Thiocarbonyl-Based Hole Transport Materials with Enhanced Defect Passivation Ability for Efficient and Stable Perovskite Solar Cells.

Organic hole transporting materials (HTMs) are extensively studied in perovskite solar cells (PSCs). The HTMs directly contact the underlying perovskite material, and they play additional roles apart from hole transporting. Developing organic HTMs with defect passivation function has been proved to be an efficient strategy to construct efficient and stable PSCs. In this work, new organic molecules with thiocarbonyl (C═S) and carbonyl (C═O) functional groups are synthesized and applied as HTMs (named FN-S and FN-O). FN-S with C═S can be facilely obtained from FN-O containing C═O. Notably, the C═S in FN-S results in superior defect passivation ability compared to FN-O. Moreover, FN-S exhibits excellent hole extraction/transport capability. Conventional PSCs using FN-S as HTM show an impressive power conversion efficiency (PCE) of 23.25%, with excellent long-term stability and operational stability. This work indicates that simply converting C═O to C═S is an efficient way to improve the device performance by strengthening the defect passivation functionality.

Improvement of Perovskite Solar Cells Efficiency by Management of the Electron Withdrawing Groups in Hole Transport Materials: Theoretical Calculation and Experimental Verification.

Management of functional groups in hole transporting materials (HTMs) is a feasible strategy to improve perovskite solar cells (PSCs) efficiency. Therefore, starting from the carbazole-diphenylamine-based JY7 molecule, JY8 and JY9 molecules are incorporated into the different electron-withdrawing groups of fluorine and cyano groups on the side chains. The theoretical results reveal that the introduction of electron-withdrawing groups of JY8 and JY9 can improve these highest occupied molecular orbital (HOMO) energy levels, intermolecular stacking arrangements, and stronger interface adsorption on the perovskite. Especially, the results of molecular dynamics (MD) indicate that the fluorinated JY8 molecule can yield a preferred surface orientation, which exhibits stronger interface adsorption on the perovskite. To validate the computational model, the JY7-JY9 are synthesized and assembled into PSC devices. Experimental results confirm that the HTMs of JY8 exhibit outstanding performance, such as high hole mobility, low defect density, and efficient hole extraction. Consequently, the PSC devices based on JY8 achieve a higher PCE than those of JY7 and JY9. This work highlights the management of the electron-withdrawing groups in HTMs to realize the goal of designing HTMs for the improvement of PSC efficiency.

Passive localization and reconstruction of multiple non-line-of-sight objects in a scene with a large visible transmissive window.

Passive non-line-of-sight imaging methods have been demonstrated to be capable of reconstructing images of hidden objects. However, current passive non-line-of-sight imaging methods have performance limitations due to the requirements of an occluder and aliasing between multiple objects. In this paper, we propose a method for passive localization and reconstruction of multiple non-line-of-sight objects in a scene with a large visible transmissive window. The analysis of the transport matrix revealed that more redundant information is acquired in a scene with a window than that with an occluder, which makes the image reconstruction more difficult. We utilized the projection operator and residual theory to separate the reconstruction equation of multiple objects into the independent equations of the located objects that can be reconstructed independently by TVAL3 and Split-Bregman algorithms, which greatly reduces the computational complexity of the reconstruction. Our method lays the foundation for multiple objects reconstruction in complex non-line-of-sight scenes.

Pathological response to neoadjuvant chemoradiotherapy for oesophageal squamous cell carcinoma in Eastern versus Western countries: meta-analysis.

OBJECTIVE: Locally advanced oesophageal squamous cell carcinoma can be treated with neoadjuvant chemoradiotherapy or chemotherapy followed by oesophagectomy. Discrepancies in pathological response rates have been reported between studies from Eastern versus Western countries. The aim of this study was to compare the pathological response to neoadjuvant chemoradiotherapy in Eastern versus Western countries. METHODS: Databases were searched until November 2022 for studies reporting pCR rates after neoadjuvant chemoradiotherapy for oesophageal squamous cell carcinoma. Multi-level meta-analyses were performed to pool pCR rates separately for cohorts from studies performed in centres in the Sinosphere (East) or in Europe and the Anglosphere (West). RESULTS: For neoadjuvant chemoradiotherapy, 51 Eastern cohorts (5636 patients) and 20 Western cohorts (3039 patients) were included. Studies from Eastern countries included more men, younger patients, more proximal tumours, and more cT4 and cN+ disease. Patients in the West were more often treated with high-dose radiotherapy, whereas patients in the East were more often treated with a platinum + fluoropyrimidine regimen. The pooled pCR rate after neoadjuvant chemoradiotherapy was 31.7% (95% c.i. 29.5% to 34.1%) in Eastern cohorts versus 40.4% (95% c.i. 35.0% to 45.9%) in Western cohorts (fixed-effect P = 0.003). For cohorts with similar cTNM stages, pooled pCR rates for the East and the West were 32.5% and 41.9% respectively (fixed-effect P = 0.003). CONCLUSION: The pathological response to neoadjuvant chemoradiotherapy is less favourable in patients treated in Eastern countries compared with Western countries. Despite efforts to investigate accounting factors, the discrepancy in pCR rate cannot be entirely explained by differences in patient, tumour, or treatment characteristics.

Applications of Metals and Metal Compounds in Improving the Sensitivity of Microfluidic Biosensors - A Review.

The enhancement of detection sensitivity in microfluidic sensors has been a continuously explored field. Initially, many strategies for sensitivity improvement involved introducing enzyme cascade reactions, but enzyme-based reactions posed challenges in terms of cost, stability, and storage. Therefore, there is an urgent need to explore enzyme-free cascade amplification methods, which are crucial for expanding the application range and improving detection stability. Metal or metal compound nanomaterials have gained great attention in the exploitation of microfluidic sensors due to their ease of preparation, storage, and lower cost. The unique physical properties of metallic nanomaterials, including surface plasmon resonance, surface-enhanced Raman scattering, metal-enhanced fluorescence, and surface-enhanced infrared absorption, contribute significantly to enhancing detection capabilities. The metal-based catalytic nanomaterials, exemplified by Fe3O4 nanoparticles and metal-organic frameworks, are considered viable alternatives to biological enzymes due to their excellent performance. Herein, we provide a detailed overview of the applications of metals and metal compounds in improving the sensitivity of microfluidic biosensors. This review not only highlights the current developments but also critically analyzes the challenges encountered in this field. Furthermore, it outlines potential directions for future research, contributing to the ongoing development of microfluidic biosensors with improved detection sensitivity.

Electronic dynamics through conical intersections via non-Markovian stochastic Schrödinger equation with complex modes.

Conical intersections (CIs) play a crucial role in photochemical reactions, offering an efficient channel for ultrafast non-adiabatic relaxation of excited states. This significantly influences the reaction pathways and the resulting products. In this work, we utilize the non-Markovian stochastic Schrödinger equation with complex modes method to explore the dynamics of electronic transitions through conical intersections (CIs) in pyrazine. The linear vibronic coupling model serves as the foundational framework, incorporating both intra-state and inter-state electron-vibrational interactions. The dynamics of the excited electronic transitions are analyzed across varying strengths of system-bath coupling and different bath relaxation times. The accuracy of this method is demonstrated by comparing its predictions with those from the hierarchical equations of motion method.

Differentiating low-risk thymomas from high-risk thymomas: preoperative radiomics nomogram based on contrast enhanced CT to minimize unnecessary invasive thoracotomy.

BACKGROUND: This study was designed to develop a combined radiomics nomogram to preoperatively predict the risk categorization of thymomas based on contrast-enhanced computed tomography (CE-CT) images. MATERIALS: The clinical and CT data of 178 patients with thymoma (100 patients with low-risk thymomas and 78 patients with high-risk thymomas) collected in our hospital from March 2018 to July 2023 were retrospectively analyzed. The patients were randomly divided into a training set (n = 125) and a validation set (n = 53) in a 7:3 ratio. Qualitative radiological features were recorded, including (a) tumor diameter, (b) location, (c) shape, (d) capsule integrity, (e) calcification, (f) necrosis, (g) fatty infiltration, (h) lymphadenopathy, and (i) enhanced CT value. Radiomics features were extracted from each CE-CT volume of interest (VOI), and the least absolute shrinkage and selection operator (LASSO) algorithm was performed to select the optimal discriminative ones. A combined radiomics nomogram was further established based on the clinical factors and radiomics scores. The differentiating efficacy was determined using receiver operating characteristic (ROC) analysis. RESULTS: Only one clinical factor (incomplete capsule) and seven radiomics features were found to be independent predictors and were used to establish the radiomics nomogram. In differentiating low-risk thymomas (types A, AB, and B1) from high-risk ones (types B2 and B3), the nomogram demonstrated better diagnostic efficacy than any single model, with the respective area under the curve (AUC), accuracy, sensitivity, and specificity of 0.974, 0.921, 0.962 and 0.900 in the training cohort, 0.960, 0.892, 0923 and 0.897 in the validation cohort, respectively. The calibration curve showed good agreement between the prediction probability and actual clinical findings. CONCLUSIONS: The nomogram incorporating clinical factors and radiomics features provides additional value in differentiating the risk categorization of thymomas, which could potentially be useful in clinical practice for planning personalized treatment strategies.

Characteristics and clinical significance of tertiary lymphoid structures in OSCC.

OBJECTIVES: This study aimed to investigate the characteristics of tertiary lymphoid structures (TLSs) in oral squamous cell carcinoma (OSCC) and their association with clinical and pathological features. MATERIALS AND METHODS: 12 TLS-related chemokines in TCGA database were analyzed to investigate the TLSs in OSCC. The density, maturity, and location of TLSs in a large cohort of 189 OSCC patients (114 of which had clinical and prognostic information) were assessed. And the significance between TLSs and clinicopathologic characteristics was analyzed. RESULTS: Bioinformatics and analysis showed that TLSs were associated with better clinical outcomes in OSCC. Histological staining and analysis showed that the overall survival rate of the high-density group (71/112, 63.4%) was significantly higher (p < 0.0001) than that of the low-density group (41/112, 36.6%), and the high-density group had fewer lymph node metastases (50.0%/68.3%, p = 0.021). And TLSs were divided into 4 types according to the maturity and location. Different types of TLSs are associated with prognosis (OS, p < 0.0001), clinical features (T stage, p = 0.028; degree of differentiation, p = 0.043), and precancerous lesion types (OSF, p = 0.049) of OSCC patients. CONCLUSION: TLSs were closely associated with better OSCC prognosis, and a more systematic classification may better guide the formulation of further treatment options.

The interconnection of orthographic, phonetic, and semantic skills with arithmetic fluency.

Arithmetic fluency is considered considers highly rely on language processing, encompassing essential skills. However, the independent predictive power of phonetic, semantic, or orthographic skills in relation to arithmetic fluency remains an unresolved query. This study introduces the common component hypothesis to elucidate the inconsistent findings in previous research. The hypothesis posits that significant correlations between language and mathematics hinge on whether the language and mathematics utilized in a given task share a common component. According to this hypothesis, processing skills for each of the three fundamental language elements (i.e., phonetic, semantic, orthographic) should correlate with arithmetic fluency, as these elements are also integral to simple arithmetic processing. A cohort of one hundred and ninety-eight primary school students participated in the study, undertaking a battery of tests assessing general cognitive abilities, psycholinguistic elements, and arithmetic fluency. The results showed that orthographic, phonetic, and semantic abilities independently predicted arithmetic fluency, even after accounting for all other cognitive predictors. These findings substantiate the common component hypothesis, providing empirical support for explaining the association between language and mathematics. This evidence contributes to addressing the interplay between language and mathematics in educational contexts.

Advanced photocatalytic disinfection mechanisms and their challenges.

Currently, microbial contamination issues have globally brought out a huge health threat to human beings and animals. To be specific, microorganisms including bacteria and viruses display durable ecological toxicity and various diseases to aquatic organisms. In the past decade, the photocatalytic microorganism inactivation technique has attracted more and more concern owing to its green, low-cost, and sustainable process. A variety kinds of photocatalysts have been employed for killing microorganisms in the natural environment. However, two predominant shortcomings including low activity of photocatalysts and diverse impacts of water characteristics are still displayed in the current photocatalytic disinfection system. So far, various strategies to improve the inherent activity of photocatalysts. Other than the modification of photocatalysts, the optimization of environments of water bodies has been also conducted to enhance microorganisms inactivation. In this mini-review, we outlined the recent progress in photocatalytic sterilization of microorganisms. Meanwhile, the relevant methods of photocatalyst modification and the influences of water body characteristics on disinfection ability were thoroughly elaborated. More importantly, the relationships between strategies for constructing advanced photocatalytic microorganism inactivation systems and improved performance were correlated. Finally, the perspectives on the prospects and challenges of photocatalytic disinfection were presented. We sincerely hope that this critical mini-review can inspire some new concepts and ideas in designing advanced photocatalytic disinfection systems.

Electronically Manipulated Molecular Strategy Enabling Highly Efficient Tin Perovskite Photovoltaics.

Buried interface modification can effectively improve the compatibility between interfaces. Given the distinct interface selections in perovskite solar cells (PSCs), the applicability of a singular modification material remains limited. Consequently, in response to this challenge, we devised a tailored molecular strategy based on the electronic effects of specific functional groups. Therefore, we prepared three distinct silane coupling agents, and due to the varying inductive effects of these functional groups, the electronic distribution and molecular dipole moments of the coupling agents are correspondingly altered. Among them, trimethoxy (3,3,3-trifluoropropyl)-silane (F3 -TMOS), which possesses electron-withdrawing groups, generates a molecular dipole moment directed toward the hole transport layer (HTL). This approach changes the work function of the HTL, optimizes the energy level alignment, reduces the open-circuit voltage loss, and facilitates carrier transport. Furthermore, through the buffering effect of the coupling agent, the interface strain and lattice distortion caused by annealing the perovskite are reduced, enhancing the stability of the tin-based perovskite. Encouragingly, tin PSCs treated with F3 -TMOS achieved a champion efficiency of 14.67 %. This strategy provides an expedient avenue for the design of buried interface modification materials, enabling precise molecular adjustments in accordance with distinct interfacial contexts to ameliorate mismatched energetics and enhance carrier dynamics.

Chemical Reaction Modulated Low-Dimensional Phase Toward Highly Efficient Sky-Blue Perovskite Light-Emitting Diodes.

Blue perovskite light-emitting diodes (PeLEDs) are crucial avenues for achieving full-color displays and lighting based on perovskite materials. However, the relatively low external quantum efficiency (EQE) has hindered their progression towards commercial applications. Quasi-two-dimensional (quasi-2D) perovskites stand out as promising candidates for blue PeLEDs, with optimized control over low-dimensional phases contributing to enhanced radiative properties of excitons. Herein, the impact of organic molecular dopants on the crystallization of various n-phase structures in quasi-2D perovskite films. The results reveal that the highly reactive bis(4-(trifluoromethyl)phenyl)phosphine oxide (BTF-PPO) molecule could effectively restrain the formation of organic spacer cation-ordered layered perovskite phases through chemical reactions, simultaneously passivate those uncoordinated Pb2+ defects. Consequently, the prepared PeLEDs exhibited a maximum EQE of 16.6 % (@ 490 nm). The finding provides a new route to design dopant molecules for phase modulation in quasi-2D PeLEDs.

Numerical analysis of MICP treated sand based on bio-chemo-hydro model.

Microbially Induced Calcite Precipitation (MICP) represents an environmentally friendly and innovative soil grouting technology. Involving intricate biochemical processes, it poses challenges for a thorough investigation of factors influencing microbial grouting effectiveness through experimentation alone. Consequently, A three-dimensional numerical model was developed to predict the permeability of bio-grouting in porous media. The numerical model is validated by comparing its results with test results available in the literature. The validated model is then used to investigate the effects of variation bacterial solution concentration, cementation solution concentration, grouting rate and grouting time on grouting effectiveness. It was founded that the remediation effect was positively correlated with the bacterial solution concentration and the number of grouting. An increased grouting rate enhanced the transport efficiency of reactants. Additionally, the concentration of cementation solution exhibited no significant effect on the reduction of calcium carbonate yield and permeability.