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Glaucoma, a leading cause of irreversible blindness worldwide, is characterized by progressive loss of retinal ganglion cells (RGCs) and optic nerve damage. While elevated intraocular pressure (IOP) is the only known modifiable risk factor, normal-tension glaucoma (NTG) challenges this notion, suggesting other mechanisms beyond IOP may contribute to its development. Emerging evidence support the hypothesis that glaucoma may be an autoimmune disease. This review summarizes evidence for this hypothesis, focusing on the gut-retina axis. We discuss how antigens of gut bacterial prime peripheral T cells to breach the blood-retina barrier (BRB) and initiate cross-reactivity with ocular tissues via molecular mimicry, resulting in autoimmune RGC damage. Understanding these mechanisms may uncover new diagnostic biomarkers and therapeutic strategies targeting immune pathways alongside conventional IOP-lowering treatments.
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OBJECTIVE: To retrospectively analyze the efficacy and safety of laser ablation (LA) and microwave ablation (MWA) in the treatment of papillary thyroid microcarcinoma (PTMC). METHODS: This was a retrospective study of 103 patients (109 nodules) who underwent thermal ablation for PTMC between October 2019 and March 2023; 61 underwent LA and 48 underwent MWA. The mean patients' age was 43.50 ± 12.42 years. After ablation, changes in tumor size at different time points, local recurrence, new lesions, lymph node metastasis, and complications were evaluated and recorded. The feasibility, success rate, and safety of LA and MWA were analyzed. RESULTS: Complete absence of enhancement on contrast-enhanced ultrasonography was observed in all target tumors after ablation. At the last follow-up, the mean volume of the PTMC nodules decreased from 0.09 ± 0.09 to 0.03 ± 0.03 ml (LA group) and from 0.11 ± 0.10 to 0.06 ± 0.08 ml (MWA group) (both, P < 0.05). There was no significant difference in volume change between the groups (P (groups): 0.520; P (groups over time): 0.423), indicating similar efficacy between the groups. There was also no significant difference in the volume reduction rate between the groups during follow-up, except for at 3 months (P = 0.023). The complication rates did not differ between the LA group (8.2 %) and MWA group (6.3 %) (P > 0.05). CONCLUSION: During the short-term follow-up, ultrasound-guided LA and MWA were effective and safe for PTMC, and there were no significant differences in treatment outcomes between the methods.
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FMR1 autosomal homolog 1 (FXR1) is an RNA-binding protein that belongs to the Fragile X-related protein (FXR) family. FXR1 is critical for development, as its loss of function is intolerant in humans and results in neonatal death in mice. Although FXR1 is expressed widely including the brain, functional studies on FXR1 have been mostly performed in cancer cells. Limited studies have demonstrated the importance of FXR1 in the brain. In this review, we will focus on the roles of FXR1 in brain development and pathogenesis of brain disorders. We will summarize the current knowledge in FXR1 in the context of neural biology, including structural features, isoform diversity and nomenclature, expression patterns, post-translational modifications, regulatory mechanisms, and molecular functions. Overall, FXR1 emerges as an important regulator of RNA metabolism in the brain, with strong implications in neurodevelopmental and psychiatric disorders.
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BACKGROUND AND AIMS: Metabolic dysfunction-associated steatohepatitis (MASH)-related fibrosis is reversible. However, the dynamic morphology change in fibrosis regression remains unclear. We aim to explore the morphological characteristics of fibrosis regression in advanced MASH patients. METHODS: Clinical and histological data of 79 biopsy-proved MASH patients with advanced fibrosis (F3-F4) were reviewed. The second harmonic generation/two-photon excitation fluorescence (SHG/TPEF) image technology was used to quantitatively identify the R (regressive) septa from P (progressive) septa and PS (perisinusoidal) fibrosis. Non-invasive tests were used to compare the fibrosis level with and without R septa groups. Transcriptomics was used to explore hub genes and the underlying mechanism of the formation of R septa. RESULTS: The R septa were different from the P septa and PS fibrosis in detail collagen quantitation identified by SHG/TPEF technology. The R septa were found in MASH fibrosis-regressed patients, which met the definition of the "Beijing classification". Therefore, patients were divided into two groups according to septa morphology: with R septa (n = 10, 12.7%), and without R septa (n = 69, 87.3%). Patients with R septa had lower values in most non-invasive tests, especially for liver stiffness assessed by TE (12.3 vs. 19.4 kPa, p = 0.010) and FAST (FibroScan®-AST) score (0.43 vs. 0.70, p = 0.003). Transcriptomics analysis showed that the expressions of five hub fibrogenic genes, including Col3A1, BGN, Col4A1, THBS2, and Col4A2 in the R septa group, were significantly lower. CONCLUSIONS: The R septa can be differentiated from the P septa and PS fibrosis by quantitative assessment of SHG/TPEF, and it represents a tendency of fibrosis regression in MASH patients. TRIAL REGISTRATION: NCT03386890, 29/12/2017.
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Lactic acid bacteria (LAB) are the main probiotics currently available in the markets and are essential for maintaining gut health. To guarantee probiotic function, it is imperative to boost the culture yield of probiotic organisms, ensure the sufficient viable cells in commercial products, or develop effective prebiotics. Recent studies have shown that protein hydrolysates and their derived peptides promote the proliferation of probiotic in vitro and the abundance of gut flora. This article comprehensively reviews different sources of protein hydrolysates and their derived peptides as growth-promoting factors for probiotics including Lactobacillus, Bifidobacterium, and Saccharomyces. We also provide a preliminary analysis of the characteristics of LAB proteolytic systems focusing on the correlation between their elements and growth-promoting activities. The structure-activity relationship and underlying mechanisms of growth-promoting peptides and their research perspectives are thoroughly discussed. Overall, this review provides valuable insights into growth-promoting protein hydrolysates and their derived peptides for proliferating probiotics in vivo or in vitro, which may inspire researchers to explore new options for industrial probiotics proliferation, dairy products fermentation, and novel prebiotics development in the future.
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The residual bone tumor and defects which is caused by surgical therapy of bone tumor is a major and important problem in clinicals. And the sequential treatment for irradiating residual tumor and repairing bone defects has wildly prospects. In this study, we developed a general modification strategy by gallic acid (GA)-assisted coordination chemistry to prepare black calcium-based materials, which combines the sequential photothermal therapy of bone tumor and bone defects. The GA modification endows the materials remarkable photothermal properties. Under the near-infrared (NIR) irradiation with different power densities, the black GA-modified bone matrix (GBM) did not merely display an excellent performance in eliminating bone tumor with high temperature, but showed a facile effect of the mild-heat stimulation to accelerate bone regeneration. GBM can efficiently regulate the microenvironments of bone regeneration in a spatial-temporal manner, including inflammation/immune response, vascularization and osteogenic differentiation. Meanwhile, the integrin/PI3K/Akt signaling pathway of bone marrow mesenchymal stem cells (BMSCs) was revealed to be involved in the effect of osteogenesis induced by the mild-heat stimulation. The outcome of this study not only provides a serial of new multifunctional biomaterials, but also demonstrates a general strategy for designing novel blacked calcium-based biomaterials with great potential for clinical use.
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We reported a surface ligand manipulation strategy for hybrid MAPbI3 perovskite quantum dots (PeQDs) using methylamine iodide (MAI), methylamine thiocyanate (MASCN) and methylamine acetate (MAAc) salts. After MAI salt post-treatment, a record high efficiency of 14.98% was obtained for MAPbI3 PeQD solar cells together with enhanced ambient stability.
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As one of the least energy-efficient components in buildings, transparent building envelopes are responsible for approximately 60% of the total energy losses. Although controlling solar transmittance through electrochromic modulation is an effective method for temperature management in these structures, a dynamic control strategy for solar light on curved transparent building envelopes is still lacking. In this study, we introduce a dual-mode flexible electrochromic device based on reversible silver deposition for curved transparent building envelopes. The device operates by reversibly depositing and dissolving silver on a flexible polyethylene terephthalate-indium tin oxide (PET-ITO) substrate, controlled through the application and removal of pulsed voltage. This mechanism enables rapid switching between radiative cooling and solar heating modes, leading to modulation of solar reflectance from 89.1% to 15.7% and solar transmittance from 0.02% to 72.9%. Under approximately 700 W/m2 of solar irradiance, the device achieves an average temperature reduction of 1.6 °C (with a maximum reduction of 4.3 °C) compared to ambient temperature in radiative cooling mode. In solar heating mode, the device achieves an average temperature increase of 17.1 °C (with a maximum increment of 23.7 °C) compared to ambient temperature. Simulation results show that the dual-mode flexible electrochromic device could offer all-season thermal regulation for curved transparent building envelopes and achieve a maximum of over 50% annual HVAC energy savings.
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19F magnetic resonance imaging (19F MRI) is gaining attention as an emerging diagnostic technology. Effective 19F MRI contrast agents (CAs) for in vivo applications require a long transverse (or spin-spin) relaxation time (T2), short longitudinal (or spin-lattice) relaxation time (T1), high fluorine content, and excellent biocompatibility. Here, we present a novel hyperbranched polymeric 19F MRI CA based on ß-cyclodextrin and phosphorylcholine. The influence of the branching degree and fluorine content on T2 was thoroughly investigated. Results demonstrated a maximum fluorine content of 11.85% and a T2 of 612 ms. This hyperbranched polymeric 19F MRI CA exhibited both great biocompatibility against cells and organs of mice and high-performance imaging capabilities both in vitro and in vivo. The research provides positive insights into the synthesis strategies, topological design, and selection of fluorine tags for 19F MRI CAs.
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Systemic lupus erythematosus (SLE) is an autoimmune disease that affects multiple organs and systems. Ocular involvement is estimated to manifest in one-third of individuals with SLE, of which lupus retinopathy and choroidopathy represent the severe subtype accompanied by vision impairment. Advancements in multimodal ophthalmic imaging have allowed ophthalmologists to reveal subclinical microvascular and structural changes in fundus of patients with SLE without ocular manifestations. Both ocular manifestations and subclinical fundus damage have been shown to correlate with SLE disease activity and, in some patients, even precede other systemic injuries as the first presentation of SLE. Moreover, ocular fundus might serve as a window into the state of systemic vasculitis in patients with SLE. Given the similarities of the anatomy, physiological and pathological processes shared among ocular fundus, and other vital organ damage in SLE, such as kidney and brain, it is assumed that ocular fundus involvement has implications in the diagnosis and evaluation of other systemic impairments. Therefore, evaluating the fundus characteristics of patients with SLE not only contributes to the early diagnosis and intervention of potential vision damage, but also holds considerate significance for the evaluation of SLE vasculitis state and prediction of other systemic injuries.
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Fundo de Olho , Lúpus Eritematoso Sistêmico , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Doenças Retinianas/etiologia , Doenças Retinianas/diagnóstico , Doenças Retinianas/patologia , Doenças da Coroide/etiologia , Doenças da Coroide/diagnósticoRESUMO
Metal-organic frameworks (MOFs) are metal-organic skeleton compounds composed of self-assembled metal ions or clusters and organic ligands. MOF materials often have porous structures, high specific surface areas, uniform and adjustable pores, high surface activity and easy modification and have a wide range of prospects for application. MOFs have been widely used. In recent years, with the continuous expansion of MOF materials, they have also achieved remarkable results in the field of antimicrobial agents. In this review, the structural composition and synthetic modification of MOF materials are introduced in detail, and the antimicrobial mechanisms and applications of these materials in the healing of infected wounds are described. Moreover, the opportunities and challenges encountered in the development of MOF materials are presented, and we expect that additional MOF materials with high biosafety and efficient antimicrobial capacity will be developed in the future.
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Estruturas Metalorgânicas , Cicatrização , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Cicatrização/efeitos dos fármacos , Humanos , Animais , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Antibacterianos/farmacologia , Antibacterianos/química , Porosidade , Infecção dos Ferimentos/tratamento farmacológicoRESUMO
Near-infrared region (NIR; 650-1700 nm) dyes offer many advantages over traditional dyes with absorption and emission in the visible region. However, developing new NIR dyes, especially organic dyes with long wavelengths, small molecular weight, and excellent stability and biocompatibility, is still quite challenging. Herein, we present a general method to enhance the absorption and emission wavelengths of traditional fluorophores by simply appending a charge separation structure, dihydropyridopyrazine. These novel NIR dyes not only exhibited greatly redshifted wavelengths compared to their parent dyes, but also displayed a small molecular weight increase together with retained stability and biocompatibility. Specifically, dye NIR-OX, a dihydropyridopyra-zine derivative of oxazine with a molecular mass of 386.2 Da, exhibited an absorption at 822 nm and an emission extending to 1200 nm, making it one of the smallest molecular-weight NIR-II emitting dyes. Thanks to its rapid metabolism and long wave-length, NIR-OX enabled high-contrast bioimaging and assessment of cholestatic liver injury in vivo and also facilitated the evalua-tion of the efficacy of liver protection medicines against cholestatic liver injury.
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BACKGROUND: Lymph node metastasis (LNM) is the primary mode of metastasis in gastric cancer (GC). However, the precise mechanisms underlying this process remain elusive. Tumor cells necessitate lipid metabolic reprogramming to facilitate metastasis, yet the role of lipoprotein lipase (LPL), a pivotal enzyme involved in exogenous lipid uptake, remains uncertain in tumor metastasis. Therefore, the aim of this study was to investigate the presence of lipid metabolic reprogramming during LNM of GC as well as the role of LPL in this process. METHODS: Intracellular lipid levels were quantified using oil red O staining, BODIPY 493/503 staining, and flow cytometry. Lipidomics analysis was employed to identify alterations in intracellular lipid composition following LPL knockdown. Protein expression levels were assessed through immunohistochemistry, Western blotting, and enzyme-linked immunosorbent assays. The mouse popliteal LNM model was utilized to investigate differences in LNM. Immunoprecipitation and mass spectrometry were employed to examine protein associations. In vitro phosphorylation assays and Phos-tag sodium dodecyl-sulfate polyacrylamide gel electrophoresis assays were conducted to detect angiopoietin-like protein 4 (ANGPTL4) phosphorylation. RESULTS: We identified that an elevated intracellular lipid level represents a crucial characteristic of node-positive (N+) GC and further demonstrated that a high-fat diet can expedite LNM. LPL was found to be significantly overexpressed in N+ GC tissues and shown to facilitate LNM by mediating dietary lipid uptake within GC cells. Leptin, an obesity-related hormone, intercepted the effect exerted by ANGPTL4/Furin on LPL cleavage. Circulating leptin binding to the leptin receptor could induce the activation of inositol-requiring enzyme-1 (IRE1) kinase, leading to the phosphorylation of ANGPTL4 at the serine 30 residue and subsequently reducing its binding affinity with LPL. Moreover, our research revealed that LPL disrupted lipid homeostasis by elevating intracellular levels of arachidonic acid, which then triggered the cyclooxygenase-2/prostaglandin E2 (PGE2) pathway, thereby promoting tumor lymphangiogenesis. CONCLUSIONS: Leptin-induced phosphorylation of ANGPTL4 facilitates LPL-mediated lipid uptake and consequently stimulates the production of PGE2, ultimately facilitating LNM in GC.
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Leptina , Lipase Lipoproteica , Metástase Linfática , Neoplasias Gástricas , Lipase Lipoproteica/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Humanos , Animais , Camundongos , Leptina/metabolismo , Metabolismo dos Lipídeos , Masculino , Linhagem Celular Tumoral , Proteína 4 Semelhante a Angiopoietina/metabolismo , Feminino , FosforilaçãoRESUMO
Tumorous bone defects present significant challenges for surgical bio-reconstruction due to the dual pathological conditions of residual tumor presence and extensive bone loss following excision surgery. To address this challenge, a "thermal switch" smart bone scaffold based on the silicene nanosheet-modified decalcified bone matrix (SNS@DBM) is developed by leveraging the natural affinity between collagen and silicene, which is elucidated by molecular dynamics simulations. Benefitting from its exceptional photothermal ability, biodegradability, and bioactivity, the SNS@DBM "thermal switch" provides an integrated postoperative sequential thermotherapy for tumorous bone loss by exerting three levels of photothermal stimulation (i.e., strong, moderate, and nonstimulation). During the different phases of postoperative bioconstruction, the SNS@DBM scaffold realizes simultaneous residual tumor ablation, tumor recurrence prevention, and bone tissue regeneration. These biological effects are verified in the tumor-bearing nude mice of patient-derived tissue xenografts and critical cranium defect rats. Mechanism research prompts moderate heat stimulus generated by and coordinating with SNSs can upregulate osteogenic genes, promote macrophages M2 polarization, and intensify angiogenesis of H-type vessels. This study introduces a versatile approach to the management of tumorous bone defects.
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BACKGROUND: Leukocyte Ig-like receptor B family 4 (LILRB4) as an immune checkpoint on myeloid cells is a potential target for tumor therapy. Extensive osteolytic bone lesion is the most characteristic feature of multiple myeloma. It is unclear whether ectopic LILRB4 on multiple myeloma regulates bone lesion. METHODS: The conditioned medium (CM) from LILRB4-WT and -KO cells was used to analyze the effects of LILRB4 on osteoclasts and osteoblasts. Xenograft, syngeneic and patient derived xenograft models were constructed, and micro-CT, H&E staining were used to observe the bone lesion. RNA-seq, cytokine array, qPCR, the activity of luciferase, Co-IP and western blotting were used to clarify the mechanism by which LILRB4 mediated bone damage in multiple myeloma. RESULTS: We comprehensively analyzed the expression of LILRB4 in various tumor tissue arrays, and found that LILRB4 was highly expressed in multiple myeloma samples. The patient's imaging data showed that the higher the expression level of LILRB4, the more serious the bone lesion in patients with multiple myeloma. The conditioned medium from LILRB4-WT not -KO cells could significantly promote the differentiation and maturation of osteoclasts. Xenograft, syngeneic and patient derived xenograft models furtherly confirmed that LILRB4 could mediate bone lesion of multiple myeloma. Next, cytokine array was performed to identify the differentially expressed cytokines, and RELT was identified and regulated by LILRB4. The overexpression or exogenous RELT could regenerate the bone damage in LILRB4-KO cells in vitro and in vivo. The deletion of LILRB4, anti-LILRB4 alone or in combination with bortezomib could significantly delay the progression of bone lesion of multiple myeloma. CONCLUSIONS: Our findings indicated that LILRB4 promoted the bone lesion by promoting the differentiation and mature of osteoclasts through secreting RELT, and blocking LILRB4 singling pathway could inhibit the bone lesion.
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Mieloma Múltiplo , Receptores Imunológicos , Transdução de Sinais , Mieloma Múltiplo/metabolismo , Mieloma Múltiplo/patologia , Mieloma Múltiplo/genética , Humanos , Camundongos , Animais , Receptores Imunológicos/metabolismo , Receptores Imunológicos/genética , NF-kappa B/metabolismo , Glicoproteínas de Membrana/metabolismo , Glicoproteínas de Membrana/genética , Linhagem Celular Tumoral , Osteoclastos/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Magnetic resonance imaging (MRI) has emerged as a pivotal tool in contemporary medical diagnostics, offering non-invasive and high-resolution visualization of internal structures. Contrast agents are essential for enhancing MRI resolution, accurate lesion detection, and early pathology identification. While gadolinium-based contrast agents are widely used in clinics, safety concerns have prompted exploration of metal-free alternatives, including fluorine and nitroxide radical-based MRI contrast agents. Fluorine-containing compounds exhibit excellent MRI capabilities, with 19F MRI providing enhanced resolution and quantitative assessment. Nitroxide radicals, such as PROXYL and TEMPO, offer paramagnetic properties for MRI contrast. Despite their versatility, nitroxide radicals suffer from lower relaxivity values (r1) compared to gadolinium. Dual-modal imaging, combining 1H and 19F MRI, has gained prominence for its comprehensive insights into biological processes and disease states. However, existing dual-modal agents predominantly utilize gadolinium-organic ligands without incorporating nitroxide radicals. Here, we introduce a novel dual-modal MRI contrast agent (J-CA) featuring a Janus asymmetric nanostructure synthesized via seeded emulsion polymerization and post-modification. J-CA demonstrates excellent in vitro and in vivo performance in both 19F and 1H MRI, with a T2 relaxation time of 5 ms and an r1 value of 0.31 mM-1 s-1, ensuring dual-modal imaging capability. Moreover, J-CA exhibits superior biocompatibility and organ targeting, making it a promising candidate for precise lesion imaging and disease diagnosis. This work introduces a new avenue for metal-free dual-modal MRI, addressing safety concerns associated with traditional contrast agents.
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Meios de Contraste , Imageamento por Ressonância Magnética , Nanoestruturas , Polímeros , Meios de Contraste/química , Meios de Contraste/síntese química , Imageamento por Ressonância Magnética/métodos , Animais , Camundongos , Nanoestruturas/química , Polímeros/química , Humanos , Flúor/química , Tamanho da PartículaRESUMO
The metal oxide electron transport layers (ETLs) of n-i-p perovskite solar cells (PSCs) are dominated by TiO2 and SnO2, while the efficacy of the other metal oxide ETLs still lags far behind. Herein, an emerging, economical, and environmentally friendly metal oxide, antimony oxide (Sb2Ox, x = 2.17), prepared by chemical bath deposition is reported as an alternative ETL for PSCs. The deposited Sb2Ox film is amorphous and very thin (â¼10 nm) but conformal on rough fluorine-doped tin oxide substrates, showing matched energy levels, efficient electron extraction, and then reduced nonradiative recombination in PSCs. The champion PSC based on the Sb2Ox ETL delivers an impressive power conversion efficiency of 24.7% under one sun illumination, which represents the state-of-the-art performance of all metal oxide ETL-based PSCs. Additionally, the Sb2Ox-based devices show improved operational and thermal stability compared to their SnO2-based counterparts. Armed with these findings, we believe this work offers an optional ETL for perovskites-based optoelectronic devices.
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INTRODUCTION: This study aimed to explore ocular manifestations in ANCA-associated vasculitis (AAV), focusing on granulomatosis with polyangiitis (GPA), eosinophilic granulomatosis with polyangiitis (EGPA), and microscopic polyangiitis (MPA) and to examine the associations with laboratory parameters and other systemic manifestations. METHODS: This retrospective study reviewed data from 533 AAV patients across two major Chinese medical centers from January 2016 to November 2023. Data including diagnosis, cranial manifestations of disease, ocular complications, and laboratory parameters were analyzed. Univariate and multivariable logistic regression analyses assessed associations across disease manifestations. Machine learning models were also utilized to predict the risk of retinal/eye involvement in AAV patients. RESULTS: Among 533 patients (210 GPA, 217 MPA, 99 EGPA, and 7 unclassified AAV), ocular complications were observed in 20.64% of them, with a distribution of 36.67% in GPA, 7.37% in MPA, and 18.18% in EGPA. The most common ocular manifestations included scleritis and retro-orbital mass/dacryocystitis, which were notably prevalent in GPA patients. Retinal involvement was observed in 9.09% of EGPA cases. The machine learning models yielded that eosinophil percentage (EOS%), high-sensitivity C-reactive protein (hsCRP), and CD4 + T cell/CD8 + T cell ratio (T4/T8) can predict retinal involvement. Furthermore, the white blood cell, EOS%, APTT, IgA, hsCRP, PR3-ANCA, and T4/T8 can predict eye involvement. CONCLUSION: Ocular manifestations are a prevalent complication across all forms of AAV. Predictive models developed through machine learning offer promising tools for early intervention and tailored patient care. This necessitates a multidisciplinary approach, integrating rheumatology and ophthalmology expertise for optimal patient outcomes.
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Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Humanos , Masculino , Estudos Retrospectivos , Feminino , Pessoa de Meia-Idade , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/complicações , China/epidemiologia , Idoso , Adulto , Oftalmopatias/etiologia , Poliangiite Microscópica/complicações , Granulomatose com Poliangiite/complicações , Aprendizado de Máquina , Proteína C-Reativa/análise , Esclerite/etiologia , Esclerite/epidemiologia , População do Leste AsiáticoRESUMO
Sustainable urban water management is crucial for meeting the growing demands of urban populations. This study presents a novel approach that combines time series clustering, seasonal analysis, and entropy analysis to uncover residential water consumption patterns and their drivers. Using a three-year dataset from the SmartH2o project, encompassing 374 households, we identify nine distinct water consumption patterns through time series clustering, leveraging Dynamic Time Warping (DTW) as the optimal similarity measure. Multiple linear regression reveals key household characteristics influencing water usage behaviors, such as the number of bathrooms and appliance efficiency ratings. Seasonal analysis uncovers temporal dynamics, highlighting shifts towards lower consumption during summer months and increased variability in transitional seasons. Entropy analysis quantifies the diversity and complexity of water consumption at both cluster and household levels, informing targeted interventions. This comprehensive, granular approach enables the development of personalized water conservation strategies and policies, empowering water utilities to optimize resource management and contribute to sustainable urban water practices.
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Entropia , Análise por Conglomerados , Abastecimento de Água , Humanos , População Urbana , Estações do Ano , Características da Família , Conservação dos Recursos Hídricos , CidadesRESUMO
The Chinese hamster ovary (CHO) cell is an epithelial-like cell that produces proteins with post-translational modifications similar to human glycosylation. It is widely used in the production of recombinant therapeutic proteins and monoclonal antibodies. Culturing CHO cells typically requires the addition of a certain proportion of fetal bovine serum (FBS) to maintain cell proliferation and passaging. However, serum is characterized by its complex composition, batch-to-batch variability, high cost, and potential risk of exogenous contaminants such as mycoplasma and viruses, which impact the purity and safety of the synthesized proteins. Therefore, search for serum alternatives and development of serum-free media for CHO-based protein biomanufacturing are of great significance. This review systematically summarizes the application advantages of CHO cells and strategies for high-density expression. It highlights the developmental trends of serum substitutes from human platelet lysates to animal-free extracts and microbial-derived substances and elucidates the mechanisms by which these substitutes enhance CHO cell culture performance and recombinant protein production, aiming to provide theoretical guidance for exploring novel serum alternatives and developing serum-free media for CHO cells.