Neuromodulation is crucial for advancing neuroscience and treating neurological disorders. However, traditional methods using rigid electrodes have been limited by large stimulating currents, low precision, and the risk of tissue damage. In this work, we developed a biocompatible ultraflexible electrode array that allows for both neural recording of spike firings and low-threshold, high-precision stimulation for neuromodulation. Specifically, mouse turning behavior can be effectively induced with approximately five microamperes of stimulating current, which is significantly lower than that required by conventional rigid electrodes. The array's densely packed microelectrodes enable highly selective stimulation, allowing precise targeting of specific brain areas critical for turning behavior. This low-current, targeted stimulation approach helps maintain the health of both neurons and electrodes, as evidenced by stable neural recordings after extended stimulations. Systematic validations have confirmed the durability and biocompatibility of the electrodes. Moreover, we extended the flexible electrode array to a brain-to-brain interface system that allows human brain signals to directly control mouse behavior. Using advanced decoding methods, a single individual can issue eight commands to simultaneously control the behaviors of two mice. This study underscores the effectiveness of the flexible electrode array in neuromodulation, opening new avenues for interspecies communication and potential neuromodulation applications.

Intra-tumoral microbiota, which is a potential component of the tumor microenvironment (TME), has been emerging as a key participant and driving factor in cancer. Previously, due to technical issues and low biological content, little was known about the microbial community within tumors. With the development of high-throughput sequencing technology and molecular biology techniques, it has been demonstrated that tumors harbor highly heterogeneous symbiotic microbial communities, which affect tumor progression mechanisms through various pathways, such as inducing DNA damage, activating carcinogenic pathways, and inducing an immunesuppressive environment. Faced with the harmful microbial communities in the TME, efforts have been made to develop new technologies specifically targeting the microbiome and tumor microecology. Given the success of nanotechnology in cancer diagnosis and treatment, the development of nanotechnology to regulate microscale and molecular-scale interactions occurring in the microbiome and tumor microecology holds promise for providing new approaches for cancer therapy. This article reviews the latest progress in this field, including the microbial community within tumors and its pro-cancer mechanisms, as well as the anti-tumor strategies targeting intra-tumoral microorganisms using nanotechnology. Additionally, this article delivers prospects for the potential clinical significance and challenges of anti-tumor strategies against intra-tumoral microorganisms.

Radiotherapy (RT) resistance remains a substantial challenge in cancer therapy. Although physical factors are optimizing, the biological mechanisms for RT resistance are still elusive. Herein, we explored potential reasons for this difficult problem by generating RT-resistant models for in vitro and in vivo experiments. We found that abnormal spindle-like microcephaly-associated protein (ASPM) was highly expressed in RT-resistant samples and significantly correlated with disease advance in lung adenocarcinoma. Mechanistically, ASPM helps RT-resistant cells to evade spindle checkpoint surveillance and complete cell division after irradiation through destruction of microtubule stability, with subsequent increases in chromosome mis-segregation and deteriorating chromosomal stability during mitosis. Depletion of ASPM stabilized microtubules and significantly decreased chromosome mis-segregation, restoring the sensitivity of RT-resistant cells to radiation. We further found, with bioinformatics analysis, amino acid sequence 963-1263 of ASPM as a potential new drug target for overcoming RT resistance and identified 9 drug pockets within this domain for clinical translation. Our findings suggest that ASPM is a key regulator with an important role in promoting RT resistance in non-small cell lung cancer, and that suppressing or blocking its expression could be worth exploring as therapy for a variety of RT-resistant cancers.

Amyloid-β (Aβ) deposition was an important pathomechanisms of Alzheimer's disease (AD). Aβ generation was highly regulated by beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), which is a prime drug target for AD therapy. The silence of BACE1 function to slow down Aβ production was accepted as an effective strategy for combating AD. Herein, BACE1 interfering RNA, metallothionein (MT) and ruthenium complexes ([Ru(bpy)₂dppz]²⁺) were all loaded in Prussian blue nanoparticles (PRM-siRNA). PRM-siRNA under near-infrared light irradiation showed good photothermal effect and triggered instantaneous opening of blood-brain barrier (BBB) for enhanced drug delivery. BACE1 siRNA slowed down Aβ production and Cu²⁺ chelation by metallothionein (MT) synergistically inhibited Aβ aggregation. Ruthenium (Ru) could real-timely track Aβ degradation and aggregation. The results indicated that PRM-siRNA significantly blocked Aβ aggregation and attenuated Aβ-induced neurotoxicity and apoptosis in vitro by inhibiting ROS-mediated oxidative damage and mitochondrial dysfunction through regulating the Bcl-2 family. PRM-siRNA in vivo effectively improved APP/PS1 mice learning and memory by alleviating neural loss, neurofibrillary tangles and activation of astrocytes and microglial cells in APP/PS1 mice by inhibiting BACE1, oxidative damage and tau phosphorylation. Taken together, our findings validated that BACE1 siRNA-loaded Prussian blue nanocomplexes showed enhanced BBB penetrability and AD synergy therapy.

Electrochemical reduction of carbon dioxide (CO₂) has been considered a promising route to reduce net carbon emissions and thus mitigate global warming issues. In practice, it mainly involves two processes including the CO₂ capture and subsequent electrochemical conversion. From the perfective of feasible and economic benefits, it is of practical significance to develop integrated CO₂ capture and conversion systems in an efficient way. However, a majority of studies have been currently focusing on the independent process, and the development of integrated strategies is still in the initial stage. This review mainly covers the recent progress on the integrated technologies of CO₂ capture and electrochemical conversion, including the integration strategies, mechanisms, and corresponding issues. The advantages and disadvantages of those strategies are particularly discussed, aiming to identify the viable routes for future applications. To conclude, the challenges and prospects in terms of the research direction in this field are provided, with the hope of promoting practical CO₂ utilization from the fundamental aspects.

Atomic layer deposition (ALD) technique has emerged as a fascinating tool for the design and synthesis of heterogeneous catalysts with atomic precision for energy conversion, generation, and storage applications. Here, we demonstrate the importance of the ALD for catalyst design by citing recently reported works, in particular, the emphasis has been given to the surface/interface engineering of catalysts for improving their catalytic efficiency in energy applications. To get insight into the reaction mechanism, the ALD-based routes for catalyst synthesis may revolutionize the field of sustainable energy conversion and storage. Moreover, the synthesis of supported nanoparticles with controlled shape and size has attracted great attention in catalysis owing to their unique properties. By taking advantage of the ALD, it is possible to synthesize catalysts at the atomic scale, particularly, site-selective ALD provides tremendous opportunities in catalytic efficiency and selectivity studies. Moreover, this review illustrates diverse heterogeneous catalysts with their limitations for energy-related applications and how the ALD technique can facilitate overcoming them. Finally, we deliberate the advancement in the ALD technique on heterogeneous catalyst design, and interface engineering of catalysts, and outline future perspectives of this technology in catalysis.

Electrochemical CO₂ reduction reaction (CO₂RR) has received great attention to solve CO₂- induced global warming and carbon neutrality. It is essential to enhance the electrochemical CO₂RR selectivity, activity, and long-term stability for sustainable manufacturing of specific chemicals via CO₂RR. To produce multi-carbon (C₂₊) chemicals, Cu-based heterogeneous catalysts have been developed in terms of defect engineering, morphological design, and facet control. Despite the substantial efforts for the design of efficient Cu-based heterogeneous catalysts, there exist inevitable structural changes of catalysts with continuous dissolution and redeposition during CO₂RR. This reconstruction modifies the as-synthesized catalysts into an unpredictable structure and leads to changes in active site. Here, we review the reconstruction of Cu-based catalysts during CO₂RR, which occurs via continuous dissolution and redeposition process. This includes fundamental principles of reconstruction and the effect of microenvironment on reconstruction during CO₂RR. We offer research progress about the reconstruction of Cu-based electrocatalysts, analysis methodologies to track the reconstruction, and the insight to improve the activity, selectivity, and stability of CO₂RR. We provide perspective to understand and harness the reconstruction for the development of efficient CO₂RR catalysts.

Cancer cells are characterized by the Warburg effect, which hijacks glycolysis and hinders OXPHOS. Pyruvate dehydrogenase kinase 1 (PDK1) is a key modulator in the Warburg effect and is highly expressed in tumor cells. We utilize PROTAC technology to design compounds that could achieve long-lasting degradation on PDK1. After screening anti-tumor activity in vitro, we selected a top compound A04, among 22 chemical candidates in various structures. Compared to a conventional PDK1 inhibitor, A04 dramatically improves over 1000-fold proliferation inhibition efficacy. Besides, A04 reverses Warburg effect and causes tumor apoptosis. In vivo, A04 achieves potent therapeutic efficacy in tumor-bearing mice and dramatically prolongs their lifetime after surgery resection. For the mechanism, A04 induces immunogenic cell death and reverses immunosuppression in the TME to enhance antitumor immunoreactivity. Further, transcriptome analysis verifies the mechanisms and uncovers fluctuation in cancer related pathways. Combination with αPD-L1 improves therapeutic efficacy and promotes multiple immunocytes infiltration. In conclusion, we first utilize PROTAC technology on modulating aberrant expressed metabolic enzyme PDK1 in cancer cells and achieve a great pharmacological effect, rendering it promising for energy-aberrant cancer therapy.

Messenger RNA (mRNA) technology is revolutionizing the pharmaceutical industry owing to its superior safety profile, manufacturing capabilities, and potential applications in previously undruggable therapeutic targets. In addition to linear mRNA, such as conventional mRNA, self-amplifying mRNA, and trans-amplifying mRNA, circular mRNA has emerged as a promising candidate. Circular RNA (circRNA) is a class of single-stranded RNA with a covalently closed loop structure that offers enhanced stability compared to linear RNA by resisting degradation from RNases. Recent studies have revolutionized our understanding of their biological functions, surpassing the notion that they are merely byproducts of aberrant splicing events. Given the remarkable success achieved in cancer and SARS-CoV-2/monkeypox virus (MPXV) vaccines, circRNA is being intensively investigated for gene and cell therapies. In this review, we provide an overview of circRNA biogenesis mechanisms in vivo, along with synthesis strategies in vitro, while discussing translation regulation mechanisms and quality control processes involved in circRNA production. Furthermore, we explore the potential application scenarios for circRNAs.

Coatings have attracted widespread attention in the field of corrosion protection of metals because of their corrosion resistance and convenient techniques. Unfortunately, till now, traditional coatings have the shortcomings of vulnerability and passive corrosion protection, hence functional coatings progressively replace them. Endowing coatings with additional functions not only transform them into active protection mechanisms but also significantly improve life cycle of coatings. However, there is only limited success in combining multiple functions of coatings, which poses considerable obstacles to further advancement of their application researches. In this paper, we summarize the research progress of self-warning and self-repairing coatings in the field of metal corrosion protection as much as possible from the perspective of functional material selection. Meanwhile, the current progress of substituting dual-functional coatings for single-functional coatings is also highlighted. We aim to provide more options and strategic guidance for the design and fabrication of functional coatings on metal surfaces and to explore the possibilities of these designs in practical applications. Last but not least, the remaining challenges and future growth regarding this field are also outlined at the end. It is hope that such an elaborately organized review will benefit the readers interested to foster more possibilities in the future.

An extracellular acidic environment and an intracellular mildly alkaline environment induced by carbonic anhydrase 9 (CA9) play a critical role in self-renewal, invasion, migration, and drug resistance of cancer stem cells (CSCs) within hypoxic solid tumors. Here, we report an antitumor strategy leveraging hyperbaric oxygen therapy (HBO) to regulate tumor pH and boost hydroxyethyl starch-doxorubicin-copper nanoparticles (HHD-Cu NPs) against CSCs. HBO overcomes tumor hypoxia, downregulates pH-regulatory proteins such as CA9, and leads to intracellular accumulation of acidic metabolites. As a result, HBO promotes intracellular acidification of both tumor cells and CSCs, triggering efficient doxorubicin release and the potent copper-mediated chemical dynamic effect of subsequently administered dual-acid-responsive HHD-Cu NPs. The combination of HBO with HHD-Cu NPs not only eliminates tumor cells but also inhibits CSCs, altogether leading to potent tumor inhibition. This study explores a new function of clinical-widely used HBO and establishes a novel combination therapy for treating CSCs abundant hypoxic solid tumors.

The concept of the microbiota-gut-brain axis has witnessed significant advancements, and observational studies revealed dysbiosis in the gut microbiota of patients with brain tumors. The causal relationship between gut microbiota and brain tumors and the potential prognostic value of microbiota are still unclear. Based on multiple Mendelian randomization analyses, this study confirms the causal effects of four gut microbes on meningioma, seven gut microbes on pituitary tumor, and eight gut microbes on glioma. Based on the Sherlock framework, this study identifies 103 meningioma-related microbe-related genes (MRGs), 40 pituitary tumor-related MRGs, and 63 glioma-related MRGs expressed in brain tissues. Almost all glioma-related MRGs are associated with tumor grade and prognosis. Lastly, the prognostic model based on machine learning and microbiota established in this study, namely microbe-related signature (MRS), could robustly predict the prognosis of glioma and provide insights for immunotherapy benefits. This study presents evidence of the causal effects of gut microbes on brain tumors, which contributes to our understanding of the microbiota-gut-brain axis. The relationship between glioma-related MRGs and glioma prognosis, along with the prognostic prediction capacity of MRS and its association with immunotherapy, provides support for the use of gut microbiota as biomarkers to evaluate the prognosis and treatment response of glioma.

Bronchiectasis frequently co-exists with chronic obstructive pulmonary disease (COPD-bronchiectasis association [CBA]). We compared the microbiota and metabolome of bronchiectasis with (BO) and without airflow obstruction (BNO), COPD, and CBA. We determined how microbiota compositions correlated with clinical characteristics and exacerbations of CBA. We prospectively recruited outpatients with BNO (n = 104), BO (n = 51), COPD (n = 33), and CBA (n = 70). We sampled at stead-state and exacerbation, and profiled sputum microbiota via 16S rRNA sequencing and metabolome via liquid chromatography/mass spectrometry. Sputum microbiota and metabolome profiles of CBA separated from COPD (P < 0.05) but not bronchiectasis, partly driven by Proteobacteria enrichment in CBA. An increasing microbial interaction but not microbiota compositions were identified at exacerbation. Pseudomonadaceae-dominant CBA yielded lower Shannon-Wiener diversity index (P < 0.001), greater bronchiectasis severity (P < 0.05) and higher future exacerbation risk (HR 2.46, 95% CI: 1.34-4.52, P < 0.001) than other genera-dominant CBA. We found a clear metabolite discrimination between CBA and COPD. Most of up-regulated metabolites identified in CBA, were amino acids metabolites, which indicated that the accumulation of amino acids metabolites was related to the alteration of airway microbiota. To conclude, airway structural changes, but not airflow limitation, correlate more profoundly with microbiota and metabolome profiles (e.g. partly via Pseudomonadaceae-amino acids metabolism links), shaping clinical outcomes of CBA.

The C─H bond is the most abundant chemical bond in organic compounds. Therefore, the development of the more direct methods for C─H bond cleavage and the elucidation of their mechanisms will provide an important theoretical basis for achieving more efficient C─H functionalization and target molecule construction. In this study, the catalyst-free photon-induced direct homolysis of C_sp3─H bonds at room temperature was discovered for the first time. The applicable substrate scope of this phenomenon is very wide, expanding from the initial benzyl compounds to aliphatic alcohols, alkanes, olefins, polymers containing benzyl hydrogens, and even gaseous methane. Experiments and calculations have demonstrated that this process involves rapid vibrational relaxation on the femtosecond time scale, leading to the formation of hydrogen radical and carbon radical. Importantly, the direct homolysis of C_sp3─H bonds is independent of the presence of oxidants, highlighting its spontaneous nature. Additionally, the cleaved hydrogen radical exhibits diverse reactivity, including coupling reactions to produce hydrogen gas (H₂), reduction of oxygen to generate hydrogen peroxide (H₂O₂), and reduction of carbon dioxide to formic acid (HCOOH). Notably, in the field of H₂O₂ production, the absence of a catalyst allows for the bypassing of inherent drawbacks associated with photocatalysts, thereby presenting significant potential for practical application. Furthermore, the cleaved carbon radicals display enhanced reactivity, providing excellent opportunities for direct functionalization, thereby enabling efficient C─H bond activation and molecular construction. Overall, this significant discovery offers a valuable new strategy for the production of bulk chemicals, organic synthesis, low-carbon and hydrogen energy industries, as well as environmental treatment.

Celastrol (CEL) is a natural pentacyclic triterpenoid demonstrating significant therapeutic properties against various diseases. However, the ambiguity of target information poses a significant challenge in transitioning CEL from a traditional remedy to a modern pharmaceutical agent. Recently, the emerging target discovery approaches of natural products have broadened extensive avenues for uncovering comprehensive target information of CEL and promoting its drug development. Herein, diverse target discovery strategies are overviewed for the pharmacological and toxicological studies of CEL, including chemical proteomics, protein microarray, degradation-based protein profiling, proteome-wide label-free approaches, network pharmacology, target-based drug screening, multi-omics analysis, and hypothesis-driven target confirmation. Dozens of CEL targets have been identified, which significantly suggests that CEL functions as a multi-target therapeutic agent. Further network interaction analysis and frequency analysis of collected targets reveal that PRDXs, HMGB1, HSP90, STAT3, and PKM2 may serve as key targets for CEL. Additionally, this review highlights the positive role of target discovery in facilitating CEL-based combination therapy and drug delivery, which is essential for further advancing the clinical applications of CEL. Efforts in CEL target identification not only aid in unraveling the scientific underpinnings of its multiple pharmacological effects but also offer crucial insights for further drug development of CEL-based drugs.

Selenium (Se) is a crucial element in selenoproteins, key biomolecules for physiological function in vivo. As a selenium-rich organ, the central nervous system can express all 25 kinds of selenoproteins, which protect neurons by reducing oxidative stress and inflammatory response. However, decreased Se levels are prevalent in a variety of neurological disorders, which is not conducive to the treatment and prognosis of patients. Thus, the biological study of Se has emerged as a focal point in investigating the pivotal role of trace elements in neuroprotection. This paper presents a comprehensive review of the pathogenic mechanism of neurological diseases, the protective mechanism of Se, and the neurological protective function of selenoproteins. Additionally, the application of Se as a neuroprotective agent in neurological disorder therapy, including ischemic stroke, Alzheimer's, Parkinson's, and other neurological diseases, is summarized. The present review aims to offer novel insights and methodologies for the prevention and treatment of neurological disorders with trace Se, providing a scientific basis for the development of innovative Se-based neuroprotectants to promote their clinical application against neurological diseases.

There is currently a pressing issue of antimicrobial resistance, with numerous pathogenic superbugs continually emerging, posing significant threats to both human health and the economy. However, the development of new antibiotics has not kept up in pace with the development of microbial resistance, necessitating the exploration of more effective approaches to combat microbes. Synthetic biology offers a novel paradigm by employing selective screening and assembling diverse biological components to redesign biological systems that can specifically target and eliminate microbes. In particular, engineering living therapeutics enables the detection and precise eradication of pathogenic microorganisms in a controlled means. This review provides an overview of recent advancements in engineering living therapeutics using synthetic biology for antibacterial treatment. It focuses on modifying bacteriophages, microbes, and mammalian cells through engineering approaches for antibacterial therapy. The advantages of each approach are delineated along with potential challenges they may encounter. Finally, a prospective outlook is presented highlighting the potential impact and future prospects of this innovative antimicrobial strategy.

Extracellular matrices (ECMs) play a crucial role in the onset and progression of tumors by providing structural support and promoting the proliferation and metastases of tumor cells. Current therapeutic approaches targeting tumor ECMs focus on two main strategies: Inhibiting matrix degradation to prevent metastases and facilitating matrix degradation to enhance the penetration of drugs and immune cells. However, these strategies may lead to unintended consequences, such as tumor growth promotion, drug resistance, and side effects like fibrotic changes in healthy tissues. Biomaterials have made significant progress in fabricating artificial ECMs for tumor therapy by inducing biomineralization, fibrogenesis, or gelation. This perspective explores the fundamental concepts, benefits, and challenges of each technique. Additionally, future improvements and research directions in artificial ECMs are discussed, highlighting their potential to advance tumor therapy.

Young migrants, particularly those at high altitudes, are predisposed to heart health abnormalities, including high-altitude heart disease. Despite the profound impact of hypobaric hypoxia on the gut microbial community, the understanding of the roles played by gut microbiota and gut microbiota-associated serum metabolites in high-altitude heart diseases remains limited. Therefore, we conducted a comprehensive multi-omics analysis involving 230 graduates from the same university, with 163 Tibetan Plateau migrants and 67 Chengdu Plain residents, and identified 206 differential metabolites (82 in serum and 124 in feces) and 369 species that differed between migrants and residents. Among these, 27 microbial species and four metabolites (Ketoglutaric acid, L-Aspartic acid, 3-Guanidinopropionic acid, betaine) detected in both serum and feces were found to be associated with migrants exhibiting compromised heart health, as diagnosed through clinical examinations. Notably, the abundances of Veillonella rogosae and Streptococcus rubneri were correlated with serum levels of L-Aspartic acid, betaine, and Ketoglutaric acid in heart health-abnormal individuals. Validation of these microbiome biomarkers and gut microbiota-associated serum metabolites in an independent cohort demonstrated their excellent predictive ability for indicating heart health abnormalities in migrants (AUC = 0.7857). Furthermore, supplementation with these identified species or gut microbiota-associated serum metabolites effectively mitigated hypobaric hypoxia-induced increases in serum lactate, glycolysis, myocardial damage, and cardiac hypertrophy. Integrated analysis revealed that the alterations in the gut microbiome negatively regulated key metabolic pathways such as the malate-aspartate shuttle, tricarboxylic acid cycle, and oxidative phosphorylation in heart health-abnormal individuals. The migration to high-altitude plateaus significantly reshaped the gut microbiome and metabolome signatures. Lower abundances of Veillonella rogosae, Streptococcus rubneri, and gut microbiota-associated serum metabolites promoted the remodeling of metabolic processes, thereby increasing susceptibility to high-altitude heart health abnormalities. Overall, our findings elucidate the microbial mechanisms underlying high-altitude heart disease and provide valuable insights for potential early intervention strategies in this context.

The role of CD8⁺ T cells in the pathogenesis of ulcerative colitis (UC) remains unclear. Similarly, the posttranscriptional regulation of the highly heterogenic CD8⁺ T cell populations and their effector function in IBD also remains poorly understood. Here, we find that miR-29a and -29b (miR-29a/b) regulate T cell fate, and their expression is higher near damaged colon tissue in patients with IBD compared to controls. In mice, we find that miR-29a/b suppresses the differentiation of CD8⁺ T cells and the secretion of pro-inflammatory and chemotactic factors during severe colitis by inhibiting transcriptional pathways, including those involving the T cell receptor and JAK-STAT signaling. Furthermore, we identify Ifng, an inflammatory factor that drives immune response and the reshaping of CD8⁺ T cell fate, as a potential target of the miRNAs. Finally, we show that delivery of miR-29 mimics to the colon of mice is sufficient to alleviate DSS-induced inflammation. Together, these data show that miR-29 plays an important role in suppressing T cell overactivation during inflammatory diseases.