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In middle to late 2023, a sublineage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron XBB, EG.5.1 (a progeny of XBB.1.9.2), is spreading rapidly around the world. We performed multiscale investigations, including phylogenetic analysis, epidemic dynamics modeling, infection experiments using pseudoviruses, clinical isolates, and recombinant viruses in cell cultures and experimental animals, and the use of human sera and antiviral compounds, to reveal the virological features of the newly emerging EG.5.1 variant. Our phylogenetic analysis and epidemic dynamics modeling suggested that two hallmark substitutions of EG.5.1, S:F456L and ORF9b:I5T are critical to its increased viral fitness. Experimental investigations on the growth kinetics, sensitivity to clinically available antivirals, fusogenicity, and pathogenicity of EG.5.1 suggested that the virological features of EG.5.1 are comparable to those of XBB.1.5. However, cryo-electron microscopy revealed structural differences between the spike proteins of EG.5.1 and XBB.1.5. We further assessed the impact of ORF9b:I5T on viral features, but it was almost negligible in our experimental setup. Our multiscale investigations provide knowledge for understanding the evolutionary traits of newly emerging pathogenic viruses, including EG.5.1, in the human population.
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OBJECTIVE: To investigate the effects of astragaloside IV (AS-IV) on podocyte injury of diabetic nephropathy (DN) and reveal its potential mechanism. METHODS: In in vitro experiment, podocytes were divided into 4 groups, normal, high glucose (HG), inositol-requiring enzyme 1 (IRE-1) α activator (HG+thapsigargin 1 µmol/L), and IRE-1α inhibitor (HG+STF-083010, 20 µmol/L) groups. Additionally, podocytes were divided into 4 groups, including normal, HG, AS-IV (HG+AS-IV 20 µmol/L), and IRE-1α inhibitor (HG+STF-083010, 20 µmol/L) groups, respectively. After 24 h treatment, the morphology of podocytes and endoplasmic reticulum (ER) was observed by electron microscopy. The expressions of glucose-regulated protein 78 (GRP78) and IRE-1α were detected by cellular immunofluorescence. In in vivo experiment, DN rat model was established via a consecutive 3-day intraperitoneal streptozotocin (STZ) injections. A total of 40 rats were assigned into the normal, DN, AS-IV [AS-IV 40 mg/(kg·d)], and IRE-1α inhibitor [STF-083010, 10 mg/(kg·d)] groups (n=10), respectively. The general condition, 24-h urine volume, random blood glucose, urinary protein excretion rate (UAER), urea nitrogen (BUN), and serum creatinine (SCr) levels of rats were measured after 8 weeks of intervention. Pathological changes in the renal tissue were observed by hematoxylin and eosin (HE) staining. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were used to detect the expressions of GRP78, IRE-1α, nuclear factor kappa Bp65 (NF-κBp65), interleukin (IL)-1ß, NLR family pyrin domain containing 3 (NLRP3), caspase-1, gasdermin D-N (GSDMD-N), and nephrin at the mRNA and protein levels in vivo and in vitro, respectively. RESULTS: Cytoplasmic vacuolation and ER swelling were observed in the HG and IRE-1α activator groups. Podocyte morphology and ER expansion were improved in AS-IV and IRE-1α inhibitor groups compared with HG group. Cellular immunofluorescence showed that compared with the normal group, the fluorescence intensity of GRP78 and IRE-1α in the HG and IRE-1α activator groups were significantly increased whereas decreased in AS-IV and IRE-1α inhibitor groups (P<0.05). Compared with the normal group, the mRNA and protein expressions of GRP78, IRE-1α, NF-κ Bp65, IL-1ß, NLRP3, caspase-1 and GSDMD-N in the HG group was increased (P<0.05). Compared with HG group, the expression of above indices was decreased in the AS-IV and IRE-1α inhibitor groups, and the expression in the IRE-1α activator group was increased (P<0.05). The expression of nephrin was decreased in the HG group, and increased in AS-IV and IRE-1α inhibitor groups (P<0.05). The in vivo experiment results revealed that compared to the normal group, the levels of blood glucose, triglyceride, total cholesterol, BUN, blood creatinine and urinary protein in the DN group were higher (P<0.05). Compared with DN group, the above indices in AS-IV and IRE-1α inhibitor groups were decreased (P<0.05). HE staining revealed glomerular hypertrophy, mesangial widening and mesangial cell proliferation in the renal tissue of the DN group. Compared with the DN group, the above pathological changes in renal tissue of AS-IV and IRE-1α inhibitor groups were alleviated. Quantitative RT-PCR and Western blot results of GRP78, IRE-1α, NF-κ Bp65, IL-1ß, NLRP3, caspase-1 and GSDMD-N were consistent with immunofluorescence analysis. CONCLUSION: AS-IV could reduce ERS and inflammation, improve podocyte pyroptosis, thus exerting a podocyte-protective effect in DN, through regulating IRE-1α/NF-κ B/NLRP3 signaling pathway.
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Rhythmic network states have been theorized to facilitate communication between brain regions, but how these oscillations influence communication subspaces, i.e, the low-dimensional neural activity patterns that mediate inter-regional communication, and in turn how subspaces impact behavior remains unclear. Using a spatial memory task in rats, we simultaneously recorded ensembles from hippocampal CA1 and the prefrontal cortex (PFC) to address this question. We found that task behaviors best aligned with low-dimensional, shared subspaces between these regions, rather than local activity in either region. Critically, both network oscillations and speed modulated the structure and performance of this communication subspace. Contrary to expectations, theta coherence did not better predict CA1-PFC shared activity, while theta power played a more significant role. To understand the communication space, we visualized shared CA1-PFC communication geometry using manifold techniques and found ring-like structures. We hypothesize that these shared activity manifolds are utilized to mediate the task behavior. These findings suggest that memory-guided behaviors are driven by shared CA1-PFC interactions that are dynamically modulated by oscillatory states, offering a novel perspective on the interplay between rhythms and behaviorally relevant neural communication.
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Advanced melanoma is an aggressive and dangerous form of skin cancer, and programmed cell death-1 (PD-1) inhibitors are recommended treatment options for patients with advanced melanoma. Mucosa-associated lymphoid tissue 1 (MALT1) impairs CD8+ T-cell activation to induce immune escape, leading to a reduction in the antitumor effect of PD-1 inhibitors. The present study aimed to assess the prognostic implication of MALT1 in patients with advanced melanoma receiving PD-1 inhibitor monotherapy. Blood MALT1 levels were assessed using reverse transcription-quantitative PCR in 20 healthy controls (HCs) after enrollment and in 49 patients with advanced melanoma before (T0), as well as 2 months (T1) and 4 months after (T2) PD-1 inhibitor monotherapy. The maximum level of MALT1 in HCs (3.100) was used as the cut-off in patients with advanced melanoma. MALT1 levels at T0 were significantly increased in patients with advanced melanoma compared with in HCs (P<0.001). In patients with advanced melanoma, MALT1 was significantly decreased from T0 to T2 (P<0.001). Objective response rate (ORR) and disease control rate (DCR) were 28.6 and 59.2%, respectively. MALT1 levels at T1 were significantly negatively associated with overall therapeutic response (P=0.001), ORR (P=0.009) and DCR (P=0.004). MALT1 levels at T2 were significantly inversely associated with overall therapeutic response (P=0.021) and ORR (P=0.036). Moreover, MALT1 levels >3.100 at T0 (P=0.027) and T1 (P=0.045) were significantly associated with shorter progression-free survival (PFS), and MALT1 levels >3.100 at T1 were significantly associated with a poor overall survival (OS; P=0.022). Multivariate Cox regression analysis demonstrated that MALT1 levels at T0 (>3.100 vs. ≤3.100) were significantly associated with a poor PFS [hazard ratio (HR)=2.248; P=0.037], and MALT1 levels at T1 (>3.100 vs. ≤3.100) were significantly associated with a poor OS (HR=4.332; P=0.007). In conclusion, MALT1 levels are reduced following PD-1 treatment, and a high MALT1 level is associated with a poor therapeutic response and shorter survival in patients with advanced melanoma receiving PD-1 inhibitor monotherapy.
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BACKGROUND: Although several SARS-CoV-2-related coronaviruses (SC2r-CoVs) were discovered in bats and pangolins, the differences in virological characteristics between SARS-CoV-2 and SC2r-CoVs remain poorly understood. Recently, BANAL-20-236 (B236) was isolated from a rectal swab of Malayan horseshoe bat and was found to lack a furin cleavage site (FCS) in the spike (S) protein. The comparison of its virological characteristics with FCS-deleted SARS-CoV-2 (SC2ΔFCS) has not been conducted yet. METHODS: We prepared human induced pluripotent stem cell (iPSC)-derived airway and lung epithelial cells and colon organoids as human organ-relevant models. B236, SARS-CoV-2, and artificially generated SC2ΔFCS were used for viral experiments. To investigate the pathogenicity of B236 in vivo, we conducted intranasal infection experiments in hamsters. FINDINGS: In human iPSC-derived airway epithelial cells, the growth of B236 was significantly lower than that of the SC2ΔFCS. A fusion assay showed that the B236 and SC2ΔFCS S proteins were less fusogenic than the SARS-CoV-2 S protein. The infection experiment in hamsters showed that B236 was less pathogenic than SARS-CoV-2 and even SC2ΔFCS. Interestingly, in human colon organoids, the growth of B236 was significantly greater than that of SARS-CoV-2. INTERPRETATION: Compared to SARS-CoV-2, we demonstrated that B236 exhibited a tropism toward intestinal cells rather than respiratory cells. Our results are consistent with a previous report showing that B236 is enterotropic in macaques. Altogether, our report strengthens the assumption that SC2r-CoVs in horseshoe bats replicate primarily in the intestinal tissues rather than respiratory tissues. FUNDING: This study was supported in part by AMED ASPIRE (JP23jf0126002, to Keita Matsuno, Kazuo Takayama, and Kei Sato); AMED SCARDA Japan Initiative for World-leading Vaccine Research and Development Centers "UTOPIA" (JP223fa627001, to Kei Sato), AMED SCARDA Program on R&D of new generation vaccine including new modality application (JP223fa727002, to Kei Sato); AMED SCARDA Hokkaido University Institute for Vaccine Research and Development (HU-IVReD) (JP223fa627005h0001, to Takasuke Fukuhara, and Keita Matsuno); AMED Research Program on Emerging and Re-emerging Infectious Diseases (JP21fk0108574, to Hesham Nasser; JP21fk0108493, to Takasuke Fukuhara; JP22fk0108617 to Takasuke Fukuhara; JP22fk0108146, to Kei Sato; JP21fk0108494 to G2P-Japan Consortium, Keita Matsuno, Shinya Tanaka, Terumasa Ikeda, Takasuke Fukuhara, and Kei Sato; JP21fk0108425, to Kazuo Takayama and Kei Sato; JP21fk0108432, to Kazuo Takayama, Takasuke Fukuhara and Kei Sato; JP22fk0108534, Terumasa Ikeda, and Kei Sato; JP22fk0108511, to Yuki Yamamoto, Terumasa Ikeda, Keita Matsuno, Shinya Tanaka, Kazuo Takayama, Takasuke Fukuhara, and Kei Sato; JP22fk0108506, to Kazuo Takayama and Kei Sato); AMED Research Program on HIV/AIDS (JP22fk0410055, to Terumasa Ikeda; and JP22fk0410039, to Kei Sato); AMED Japan Program for Infectious Diseases Research and Infrastructure (JP22wm0125008 to Keita Matsuno); AMED CREST (JP21gm1610005, to Kazuo Takayama; JP22gm1610008, to Takasuke Fukuhara; JST PRESTO (JPMJPR22R1, to Jumpei Ito); JST CREST (JPMJCR20H4, to Kei Sato); JSPS KAKENHI Fund for the Promotion of Joint International Research (International Leading Research) (JP23K20041, to G2P-Japan Consortium, Keita Matsuno, Takasuke Fukuhara and Kei Sato); JST SPRING (JPMJSP2108 to Shigeru Fujita); JSPS KAKENHI Grant-in-Aid for Scientific Research C (22K07103, to Terumasa Ikeda); JSPS KAKENHI Grant-in-Aid for Scientific Research B (21H02736, to Takasuke Fukuhara); JSPS KAKENHI Grant-in-Aid for Early-Career Scientists (22K16375, to Hesham Nasser; 20K15767, to Jumpei Ito); JSPS Core-to-Core Program (A. Advanced Research Networks) (JPJSCCA20190008, to Kei Sato); JSPS Research Fellow DC2 (22J11578, to Keiya Uriu); JSPS Research Fellow DC1 (23KJ0710, to Yusuke Kosugi); JSPS Leading Initiative for Excellent Young Researchers (LEADER) (to Terumasa Ikeda); World-leading Innovative and Smart Education (WISE) Program 1801 from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) (to Naganori Nao); Ministry of Health, Labour and Welfare (MHLW) under grant 23HA2010 (to Naganori Nao and Keita Matsuno); The Cooperative Research Program (Joint Usage/Research Center program) of Institute for Life and Medical Sciences, Kyoto University (to Kei Sato); International Joint Research Project of the Institute of Medical Science, the University of Tokyo (to Terumasa Ikeda and Takasuke Fukuhara); The Tokyo Biochemical Research Foundation (to Kei Sato); Takeda Science Foundation (to Terumasa Ikeda and Takasuke Fukuhara); Mochida Memorial Foundation for Medical and Pharmaceutical Research (to Terumasa Ikeda); The Naito Foundation (to Terumasa Ikeda); Hokuto Foundation for Bioscience (to Tomokazu Tamura); Hirose Foundation (to Tomokazu Tamura); and Mitsubishi Foundation (to Kei Sato).
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COVID-19 , Quirópteros , SARS-CoV-2 , Animales , SARS-CoV-2/genética , SARS-CoV-2/fisiología , Humanos , COVID-19/virología , Quirópteros/virología , Glicoproteína de la Espiga del Coronavirus/metabolismo , Glicoproteína de la Espiga del Coronavirus/genética , Organoides/virología , Organoides/metabolismo , Células Madre Pluripotentes Inducidas/metabolismo , Células Madre Pluripotentes Inducidas/citología , Células Madre Pluripotentes Inducidas/virología , Cricetinae , Furina/metabolismo , Células Epiteliales/virología , Células Vero , Chlorocebus aethiopsRESUMEN
Organic transistors based on organic semiconductors together with quantum dots (QDs) are attracting more and more interest because both materials have excellent optoelectronic properties and solution processability. Electronics based on nontoxic QDs are highly desired considering the potential health risks but are limited by elevated surface defects, inadequate stability, and diminished luminescent efficiency. Herein, organic synaptic transistors based on environmentally friendly ZnSe/ZnS core/shell QDs with passivating surface defects are developed, exhibiting optically programmable and electrically erasable characteristics. The synaptic transistors feature linear multibit storage capability and wavelength-selective memory function with a retention time above 6000 s. Various neuromorphic applications, including memory enhancement, optical communication, and memory consolidation behaviors, are simulated. Utilizing an established neuromorphic model, accuracies of 92% and 91% are achieved in pattern recognition and complicated electrocardiogram signal processing, respectively. This research highlights the potential of environmentally friendly QDs in neuromorphic applications and health monitoring.
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Background: Depression is a severe mental disorder that poses a significant threat to both the physical and mental wellbeing of individuals. Currently, there are various methods for treating depression, including traditional Chinese herbal formulations like Chaihu-Shugan-San (CSS), which have shown effective antidepressant effects in both clinical and animal research. Objective: This review aims to provide a comprehensive synthesis of evidence related to CSS, considering both preclinical and clinical studies, to uncover its potential multi-level, multi-pathway, and multi-target mechanisms for treating depression and identify its active ingredients. Methods: A thorough search was conducted in electronic databases, including PubMed, MEDLINE, Web of Science, Google Scholar, CNKI, and Wanfang, using keywords such as "Chaihu Shugan" and "depression" to retrieve relevant literature on CSS and its active ingredients. The review process adhered to the PRISMA guidelines. Results: This review consolidates the mechanisms underlying antidepressant effects of CSS and its active ingredients. It emphasizes its involvement in the regulation of monoaminergic neurotransmitter systems, synaptic plasticity, and the hypothalamic-pituitary-adrenal axis, among other aspects. Conclusion: CSS exerts a pivotal role in treating depression through various pathways, including the monoaminergic neurotransmitter system, the hypothalamic-pituitary-adrenal axis, synaptic plasticity, inflammation, brain-derived neurotrophic factor levels, and the brain-gut axis. This review facilitates a comprehensive understanding of the current state of CSS research, fostering an in-depth exploration of the etiological mechanisms of depression and the potential discovery of novel antidepressant drugs.
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Plant secondary metabolites are important raw materials for the pharmaceutical industry, and their biosynthetic processes are subject to diverse and precise regulation by miRNA. The identification of miRNA molecules in medicinal plants and exploration of their mechanisms not only contribute to a deeper understanding of the molecular genetic mechanisms of plant growth, development and resistance to stress, but also provide a theoretical basis for elucidating the pharmacological effects of authentic medicinal materials and constructing bioreactors for the synthesis of medicinal secondary metabolite components. This paper summarizes the research reports on the discovery of miRNA in medicinal plants and their regulatory mechanisms on the synthesis of secondary metabolites by searching the relevant literature in public databases. It summarizes the currently discovered miRNA and their functions in medicinal plants, and summarizes the molecular mechanisms regulating the synthesis and degradation of secondary metabolites. Furthermore, it provides a prospect for the research and development of medicinal plant miRNA. The compiled information contributes to a comprehensive understanding of the research progress on miRNA in medicinal plants and provides a reference for the industrial development of related secondary metabolite biosynthesis.
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MicroARNs , Plantas Medicinales , Plantas Medicinales/genética , Plantas Medicinales/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Metabolismo Secundario/genéticaRESUMEN
Tire plastic and road-wear particles (TPR-WP) are a current research priority as one of the main environmental sources of microplastics. We selected a unique land use type - desert restoration area, collected soil and dust samples from the Yujing Expressway and its service areas, and analyzed TPR-WP abundance, type, size and morphology by laser direct infrared (LDIR). The abundance of TPR-WP in expressway dust (14,446.87 ± 10,234.24 n/kg) was higher than that in soil (7500 ± 3253.64 n/kg). Random forest model showed that the source of TPR-WP was highly correlated with economic factors and natural climate. Overall, the proportion of small and medium-sized TPR-WP in dust was higher than soil, more than half of the TPR-WP in dust were in 20 - 50 µm range. The proportion of small particle size TPR-WP increased with the rise of elevation. The pollution load index suggested that the survey region was generally at level I risk zone, while the ecological risk index indicated that the pollution level of expressway was III and IV, and the service area was IV. In general, the study was of great significance for clarifying the distribution and risk of TPR-WP in soil and dust of expressways and service areas.
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Organic ion-gated transistors (OIGTs) demonstrate commendable performance for versatile neuromorphic systems. However, due to the fragility of organic materials to organic solvents, efficient and reliable all-photolithography methods for scalable manufacturing of high-density OIGT arrays with multimode neuromorphic functions are still missing, especially when all active layers are patterned in high-density. Here, a flexible high-density (9662 devices per cm2) OIGT array with high yield and minimal device-to-device variation is fabricated by a modified all-photolithography method. The unencapsulated flexible array can withstand 1000 times' bending at a radius of 1 mm, and 3 months' storage test in air, without obvious performance degradation. More interesting, the OIGTs can be configured between volatile and nonvolatile modes, suitable for constructing reservoir computing systems to achieve high accuracy in classifying handwritten digits with low training costs. This work proposes a promising design of organic and flexible electronics for affordable neuromorphic systems, encompassing both array and algorithm aspects.
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Background: Despite the increasing global prevalence of depression, existing treatment methods have limitations. Acupuncture has been recognized for its potential to alleviate various diseases by regulating inflammatory cytokines. However, a comprehensive systematic analysis of the effects of acupuncture on depression through inflammatory cytokines is currently lacking. This review aims to evaluate the impact of acupuncture on inflammatory cytokines in animal models of depression. Methods: A comprehensive search was conducted in PubMed, EMBASE, MEDLINE, and the Research Information Service System to identify studies that met predefined inclusion and exclusion criteria. The quality of each included study was assessed using a 10-item checklist adapted from the Cochrane Collaboration methods and animal data review. Meta-analysis was performed using STATA 17.0 software for literature that met the inclusion criteria. Results: The meta-analysis included a total of 21 studies involving 376 rodents. The overall quality of the included reports was rated as moderate or higher. The results demonstrated that acupuncture had a significant effect on the reduction of pro-inflammatory cytokines, including: IL-1ß [SMD = 3.36, 95% CI (2.73, 4.00), I2 = 73.3%, p < 0.05], IL-6 [SMD = 3.05, 95% CI (2.45, 3.64), I2 = 68%, p < 0.05], and TNF-α [SMD = 3.30, 95% CI (2.53, 4.06), I2 = 74.5%, p < 0.05]. Conversely, acupuncture was associated with an increased expression of anti-inflammatory cytokines, notably: IL-4 [SMD = -1.64, 95% CI (-2.46, -0.82), I2 = 4.1%, p = 0.307] and IL-10 [SMD = -1.45, 95% CI (-2.24, -0.66), I2 = 0, p = 0.678]. These results suggest that acupuncture modulates cytokine levels in depressed rodents, including reducing the expression of pro-inflammatory cytokines and increasing the expression of anti-inflammatory cytokines, thereby regulating the immune-related antidepressant pathway. Conclusion: While this study is limited by the number of included studies, the results suggest that acupuncture may be a viable option for the treatment of depression, and this effect is achieved through the regulation of various inflammatory cytokines. Systematic review registration: This research endeavor was duly registered with PROSPERO (ID: CRD42023420919, https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=420919).
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BACKGROUND: Lung adenocarcinoma (LUAD) represents a significant global health issue. Smoking contributes to the development of periodontitis and LUAD. The connections between the two are still ambiguous. METHODS: Based on RNA expression data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, differentially expressed genes (DEGs) in Periodontitis and LUAD were collected. Protein-protein interaction (PPI) networks were produced by mining genes intersecting with crossover DEGs. Genes in the subnetwork and the top 15 genes of the topology score were defined as the crosstalk gene. Feature selection and diagnostic model construction were conducted based on Recursive Feature Elimination (RFE) and support vector machines (SVM). additionally, we analyzed the immune cells and signaling pathways influenced by the crosstalk gene. RESULTS: A total of 29 crossover DEGs between Periodontitis and LUAD were filtered, with 20 genes interacting with them in the PPI network. Five subnetworks with similar interaction patterns in the PPI network were detected. Based on the network topology analysis, genes ranking in the top 15 were used to take the intersection with those genes in the 5 subnetworks. Twelve intersecting genes were identified. Based on RFE and SVM algorithms, FKBP11 and MMP13 were considered as the Crosstalk genes for both Periodontitis and LUAD. The diagnostic model composed of FKBP11 and MMP13 showed excellent diagnostic potential. In addition, we found that FKBP11 and MMP13 influenced Macrophages, M1, T cells, CD8 activity, immune-related pathways, and cell cycle pathways. CONCLUSION: We identified the crosstalk genes (FKBP11 and MMP13) between periodontitis and LUAD. The two genes affected the comorbidity status between the two diseases through immune cell activity.
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In late 2023, several SARS-CoV-2 XBB descendants, notably EG.5.1, were predominant worldwide. However, a distinct SARS-CoV-2 lineage, the BA.2.86 variant, also emerged. BA.2.86 is phylogenetically distinct from other Omicron sublineages, accumulating over 30 amino acid mutations in its spike protein. Here, we examined the virological characteristics of the BA.2.86 variant. Our epidemic dynamics modeling suggested that the relative reproduction number of BA.2.86 is significantly higher than that of EG.5.1. Additionally, four clinically available antivirals were effective against BA.2.86. Although the fusogenicity of BA.2.86 spike is similar to that of the parental BA.2 spike, the intrinsic pathogenicity of BA.2.86 in hamsters was significantly lower than that of BA.2. Since the growth kinetics of BA.2.86 are significantly lower than those of BA.2 both in vitro and in vivo, the attenuated pathogenicity of BA.2.86 is likely due to its decreased replication capacity. These findings uncover the features of BA.2.86, providing insights for control and treatment.
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COVID-19 , Animales , Cricetinae , SARS-CoV-2/genética , Aminoácidos , Cinética , MutaciónRESUMEN
Hydrogels, formed from crosslinked hydrophilic macromolecules, provide a three-dimensional microenvironment that mimics the extracellular matrix. They served as scaffold materials in regenerative medicine with an ever-growing demand. However, hydrogels composed of only organic components may not fully meet the performance and functionalization requirements for various tissue defects. Composite hydrogels, containing inorganic components, have attracted tremendous attention due to their unique compositions and properties. Rigid inorganic particles, rods, fibers, etc., can form organic-inorganic composite hydrogels through physical interaction and chemical bonding with polymer chains, which can not only adjust strength and modulus, but also act as carriers of bioactive components, enhancing the properties and biological functions of the composite hydrogels. Notably, incorporating environmental or stimulus-responsive inorganic particles imparts smartness to hydrogels, hence providing a flexible diagnostic platform for in vitro cell culture and in vivo tissue regeneration. In this review, we discuss and compare a set of materials currently used for developing organic-inorganic composite hydrogels, including the modification strategies for organic and inorganic components and their unique contributions to regenerative medicine. Specific emphasis is placed on the interactions between the organic or inorganic components and the biological functions introduced by the inorganic components. The advantages of these composite hydrogels indicate their potential to offer adaptable and intelligent therapeutic solutions for diverse tissue repair demands within the realm of regenerative medicine.
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Hidrogeles , Medicina Regenerativa , Medicina Regenerativa/métodos , Hidrogeles/química , Matriz Extracelular/química , Sustancias Macromoleculares , Polímeros/análisis , Ingeniería de Tejidos/métodosRESUMEN
Organic optoelectronic synaptic devices that can reliably operate in high-temperature environments (i.e., beyond 121°C) or remain stable after high-temperature treatments have significant potential in biomedical electronics and bionic robotic engineering. However, it is challenging to acquire this type of organic devices considering the thermal instability of conventional organic materials and the degradation of photoresponse mechanisms at high temperatures. Here, high-temperature synaptic phototransistors (HTSPs) based on thermally stable semiconductor polymer blends as the photosensitive layer are developed, successfully simulating fundamental optical-modulated synaptic characteristics at a wide operating temperature range from room temperature to 220°C. Robust optoelectronic performance can be observed in HTSPs even after experiencing 750 h of the double 85 testing due to the enhanced operational reliability. Using HTSPs, Morse-code optical decoding scheme and the visual object recognition capability are also verified at elevated temperatures. Furthermore, flexible HTSPs are fabricated, demonstrating an ultralow power consumption of 12.3 aJ per synaptic event at a low operating voltage of -0.05 mV. Overall, the conundrum of achieving reliable optical-modulated neuromorphic applications while balancing low power consumption can be effectively addressed. This research opens up a simple but effective avenue for the development of high-temperature and energy-efficient wearable optoelectronic devices in neuromorphic computing applications.
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Pain perception nociceptors (PPN), an important type of sensory neuron, are capable of sending out alarm signals when the human body is exposed to destructive stimuli. Simulating the human ability to perceive the external environment and spontaneously avoid injury is a critical function of neural sensing of artificial intelligence devices. The demand for developing artificial PPN has subsequently increased. However, due to the application scenarios of bionic electronic devices such as human skin, electronic prostheses, and robot bodies, where a certain degree of surface deformation constantly occurs, the ideal artificial PPN should have the stretchability to adapt to real scenarios. Here, an organic semiconductor nanofiber artificial pain perception nociceptor (NAPPN) based on a pre-stretching strategy is demonstrated to achieve key pain aspects such as threshold, sensitization, and desensitization. Remarkably, while stretching up to 50%, the synaptic behaviors and injury warning ability of NAPPN can be retained. To verify the wearability of the device, NAPPN was attached to a curved human finger joint, on which PPN behaviors were successfully mimicked. This provides a promising strategy for realizing neural sensing function on either deformed or mobile electronic devices.
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Inteligencia Artificial , Nociceptores , Humanos , Células Receptoras Sensoriales , Electrónica , Percepción del DolorRESUMEN
The constant presence of infectious diseases poses an everlasting threat to the entire world. In recent years, there has been an increased attention toward the application of traditional Chinese medicine (TCM) in the treatment of emerging infectious diseases, as it has played a significant role. The aim of this article is to provide a concise overview of the roles and mechanisms of TCM in treating infectious diseases. TCM possesses the ability to modulate relevant factors, impede signaling pathways, and inhibit microbial growth, thereby exhibiting potent antiviral, antibacterial, and anti-inflammatory effects that demonstrate remarkable efficacy against viral and bacterial infections. This article concludes that the comprehensive regulatory features of Chinese herbal medicines, with their various components, targets, and pathways, result in synergistic effects. The significance of Chinese herbal medicines in the context of infectious diseases should not be underestimated; however, it is crucial to also acknowledge their underutilization. This paper presents constructive suggestions regarding the challenges and opportunities faced by Chinese medicines. Particularly, it emphasizes the effectiveness and characteristics of Chinese medicines in the treatment of infectious diseases, specifying how these medicines' active substances can be utilized to target infectious diseases. This perspective is advantageous in facilitating researchers' pharmacological studies on Chinese medicines, focusing on the specific points of action. The mechanism of action of Chinese herbal medicines in the treatment of infectious diseases is comprehensively elucidated in this paper, providing compelling evidence for the superior treatment of infectious diseases through Chinese medicine. This information is favorable for advancing the development of TCM and its potential applications in the field of infectious diseases.
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Autonomously self-propelled nanoswimmers represent the next-generation nano-devices for bio- and environmental technology. However, current nanoswimmers generate limited energy output and can only move in short distances and duration, thus are struggling to be applied in practical challenges, such as living cell transportation. Here, we describe the construction of biodegradable metal-organic framework based nanobots with chemically driven buoyancy to achieve highly efficient, long-distance, directional vertical motion to "find-and-fetch" target cells. Nanobots surface-functionalized with antibodies against the cell surface marker carcinoembryonic antigen are exploited to impart the nanobots with specific cell targeting capacity to recognize and separate cancer cells. We demonstrate that the self-propelled motility of the nanobots can sufficiently transport the recognized cells autonomously, and the separated cells can be easily collected with a customized glass column, and finally regain their full metabolic potential after the separation. The utilization of nanobots with easy synthetic pathway shows considerable promise in cell recognition, separation, and enrichment.
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Hepatocellular carcinoma (HCC) is the leading fatal malignancy worldwide. The tumor microenvironment (TME) can affect the survival, proliferation, migration, and even dormancy of cancer cells. Hypoxia is an important component of the TME, and hypoxia-inducible factor-1α (HIF-1α) is the most important transcriptional regulator. Noncoding RNAs (ncRNAs), including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), comprise a large part of the human transcriptome and play an important role in regulating the tumorigenesis of HCC. This review discusses the role of ncRNAs in hepatocarcinogenesis, epithelial-mesenchymal transition (EMT), and angiogenesis in a hypoxic microenvironment, as well as the interactions between ncRNAs and key components of the TME. It further discusses their use as biomarkers and the potential clinical value of drugs, as well as the challenges faced in the future.