Single Cell mass spectrometry: Towards quantification of small molecules in individual cells.

Studying cell heterogeneity can provide a deeper understanding of biological activities, but appropriate studies cannot be performed using traditional bulk analysis methods. The development of diverse single cell bioanalysis methods is in urgent need and of great significance. Mass spectrometry (MS) has been recognized as a powerful technique for bioanalysis for its high sensitivity, wide applicability, label-free detection, and capability for quantitative analysis. In this review, the general development of single cell mass spectrometry (SCMS) field is covered. First, multiple existing SCMS techniques are described and compared. Next, the development of SCMS field is discussed in a chronological order. Last, the latest quantification studies on small molecules using SCMS have been described in detail.

Mass Spectrometry Quantification of Anticancer Drug Uptake in Single Multicellular Tumor Spheroids.

Although most advanced-stage ovarian cancers initially respond to platinum- and taxane-based chemotherapy, the majority of them will recur and eventually develop chemoresistance. Among all drug resistance mechanisms, reduced drug uptake in tumors is regarded as an important pathway acquired by drug-resistant cancer cells. For patients with ovarian cancer, chemoresistant cells can develop into multicellular spheroids and spread through ascite fluid that accumulates in their abdomen. These spheroids consist of 3D structures that are highly heterogeneous with different shapes, sizes, and compositions of cell types. Thus, studying drug uptake at the single spheroid level is important for understanding chemosensitivity and chemoresistance; however, drug-uptake studies in single spheroids have not been previously reported due to the lack of a suitable analytical technique. In this study, we cultured spheroids using the ovarian cancer cell line (OVCAR-8) and treated them using paclitaxel or OSW-1, a natural compound with anticancer properties. We then developed a method of quantifying drug uptake in single spheroids using LC/MS measurements and then normalized the drug amount in each spheroid to its size and total protein content. Our method can be used in translational studies of drug development, treatment, and prediction of drug efficacy prior to chemotherapy.

MassLite: An integrated python platform for single cell mass spectrometry metabolomics data pretreatment with graphical user interface and advanced peak alignment method.

Mass spectrometry (MS) has been one of the most widely used tools for bioanalytical analysis due to its high sensitivity, capability of quantitative analysis, and compatibility with biomolecules. Among various MS techniques, single cell mass spectrometry (SCMS) is an advanced approach to molecular analysis of cellular contents in individual cells. In tandem with the creation of novel experimental techniques, the development of new SCMS data analysis tools is equally important. As most published software packages are not specifically designed for pretreatment of SCMS data, including peak alignment and background removal, their applicability on processing SCMS data is generally limited. Hereby we introduce a Python platform, MassLite, specifically designed for rapid SCMS metabolomics data pretreatment. This platform is made user-friendly with graphical user interface (GUI) and exports data in the forms of each individual cell for further analysis. A core function of this tool is to use a novel peak alignment method that avoids the intrinsic drawbacks of traditional binning method, allowing for more effective handling of MS data obtained from high resolution mass spectrometers. Other functions, such as void scan filtering, dynamic grouping, and advanced background removal, are also implemented in this tool to improve pretreatment efficiency.

"Bowling Collision Effect" of CoMo6 Polyoxometalate Units Enables Wide Temperature Range from -20 to 60 °C and Dendrite Mitigation Li-S Batteries.

To improve the performance of Lithium-Sulfur (Li-S) batteries, the reaction catalysts of lithium polysulfides (LiPSs) reactions should have the characteristics of large surface area, efficient atomic utilization, high conductivity, small size, good stability, and strong adjustability. Herein, Anderson-type polyoxometalate ([TMMo6O24]n-, TM = Co, Ni, Fe, represented by TMMo6 POMs) are used as the modified materials for Li-S battery separator. By customizing the central metal atoms, this work gains insights into the layer-by-layer electron transfer mechanism between TMMo6 units and LiPSs, similar to the collision effect of a bowling ball. Theoretical analysis and in situ experimental characterization show that the changes of CoMo6 units with moderate binding energy and lowest Gibbs free energy result in the formation of robust polar bonds and prolonged S─S bonds after adsorption. Hence, the representative Li-S battery with CoMo6 and graphene composite modified separator has a high initial capacity of 1588.6 mA h g-1 at 0.2 C, excellent cycle performance of more than 3000 cycles at 5 C, and uniform Li+ transport over 1900 h. More importantly, this work has revealed the inherent contradiction between the kinetics and thermodynamics, achieving a stable cycle in the temperature range of -20 to 60 °C.

Cuproptosis and Cu: a new paradigm in cellular death and their role in non-cancerous diseases.

Cuproptosis, a newly characterized form of regulated cell death driven by copper accumulation, has emerged as a significant mechanism underlying various non-cancerous diseases. This review delves into the complex interplay between copper metabolism and the pathogenesis of conditions such as Wilson's disease (WD), neurodegenerative disorders, and cardiovascular pathologies. We examine the molecular mechanisms by which copper dysregulation induces cuproptosis, highlighting the pivotal roles of key copper transporters and enzymes. Additionally, we evaluate the therapeutic potential of copper chelation strategies, which have shown promise in experimental models by mitigating copper-induced cellular damage and restoring physiological homeostasis. Through a comprehensive synthesis of recent advancements and current knowledge, this review underscores the necessity of further research to translate these findings into clinical applications. The ultimate goal is to harness the therapeutic potential of targeting cuproptosis, thereby improving disease management and patient outcomes in non-cancerous conditions associated with copper dysregulation.

Momordin Ic ameliorates psoriasis skin damage in mice via the IL-23/IL-17 axis.

Psoriasis, a chronic and easily recurring inflammatory skin disease, causes a great economic burden to the patient's family because the etiology and mechanism are still unclear and the treatment cycle is long. In this study, the function and related mechanisms of Momordin Ic in psoriasis were investigated. The IMQ-induced mouse psoriasis model was constructed. The protective effects of different doses of Momordin Ic on psoriasis skin damage in mice were detected by PASI score, HE staining and Ki-67 staining. A psoriasis-like keratinocyte model was established at the cellular level using M5 (IL-17A, IL-22, oncostatin M, IL-1α, and TNF-α) triggered HaCaT. The effects of Momordin Ic upon HaCaT cell biological behavior were examined using MTT and CCK-8 assays. In terms of mechanism, the expression level of each inflammatory factor was assessed using IHC staining and/or ELISA, qRT-PCR, the expression of oxidative stress-related indicators was detected biochemically, and western blot was performed to detect the levels of key proteins of the Wnt signaling and VEGF. As the results shown,  at the in vivo level, Momordin Ic significantly alleviated skin damage, reduced PASI score and inhibited hyperproliferation of keratinized cells in psoriasis mice. At the cellular level, Momordin Ic also significantly reversed M5-induced hyperproliferation of HaCaT keratinocytes. In terms of mechanism, Momordin Ic significantly inhibited the IL-23/IL-17 axis, dramatically elevated the levels of intracellular antioxidants including SOD, GSH-Px, and CAT, and significantly down-regulated the levels of the indicator of oxidative damage, malondialdehyde (MDA). In addition, Momordin Ic also significantly inhibited the level of ß-catenin, a pivotal protein of the Wnt signaling, C-Myc, a target gene of the Wnt signaling, and VEGF, a critical protein of angiogenesis. In conclusion, Momordin Ic can be involved in the skin-protective effects of psoriasis by multiple mechanisms, including inhibition of the Wnt signaling pathway and the IL-23/IL-17 axis, and suppression of oxidative damageand VEGF expression. Momordin Ic has been proven to be an underlying therapeutic drug for the treatment of psoriasis.

Effect of a topical traditional Chinese herbal medicine on skin microbiota in mouse model of atopic dermatitis.

This study aims to explore the impact of the herbal ointment Chushi Zhiyang Ruangao (CSZYRG) on the skin's microecological environment in a mouse model of atopic dermatitis (AD) and to understand the underlying mechanisms involved. The AD model was established in C57 mice using calpolitol (a hypocalcemic analog of vitamin D3; MC903). Medication-free matrix ointment, CSZYRG, and mometasone furoate cream (positive control group) were applied to the injured areas. The skin lesions of AD model mice were photographed. Skin lesions were applied for the hematoxylin and eosin (H&E) staining to observe any pathological changes. Serum immunoglobulin IgE was detected by enzyme-linked immunosorbent assay (ELISA). The changes in the expression of inflammation-related factors TNF-α, IL-1ß, and IL-6 in mice were detected using ELISA and qRT-PCR. Skin microflora samples were taken for 16S rDNA sequencing and analyzed for changes in the skin flora diversity, abundance, and dominant flora in mice. It was concluded that CSZYRG effectively alleviates skin lesions, serum IgE, and levels of TNF-α, IL-1ß, and IL-6 in AD model mice. However, CSZYRG did not affect the skin microbial diversity of AD model mice but could exert an effect on the skin microbial community in AD mice and the relative abundance of the dominant microflora. CSZYRG may play a therapeutic role in AD by affecting the skin microbial community and relative abundance of dominant microflora in AD mice.

Comparison of Aroma and Taste Profiles of Kiwi Wine Fermented with/without Peel by Combining Intelligent Sensory, Gas Chromatography-Mass Spectrometry, and Proton Nuclear Magnetic Resonance.

Kiwi wine (KW) is tipically made by fermenting juice from peeled kiwifruit, resulting in the disposal of peel and pomace as by-products. However, the peel contains various beneficial compounds, like phenols and flavonoids. Since the peel is edible and rich in these compounds, incorporating it into the fermentation process of KW presents a potential solution to minimize by-product waste. This study compared the aroma and taste profiles of KW from peeled (PKW) and unpeeled (UKW) kiwifruits by combining intelligent sensory technology, GC-MS, and 1H-NMR. Focusing on aroma profiles, 75 volatile organic compounds (VOCs) were identified in KW fermented with peel, and 73 VOCs in KW without peel, with 62 VOCs common to both. Among these compounds, rose oxide, D-citronellol, and bornylene were more abundant in UKW, while hexyl acetate, isoamyl acetate, and 2,4,5-trichlorobenzene were significantly higher in PKW. For taste profiles, E-tongue analysis revealed differences in the taste profiles of KW from the two sources. A total of 74 molecules were characterized using 1H-NMR. UKW exhibited significantly higher levels of tartrate, galactarate, N-acetylserotonin, 4-hydroxy-3-methoxymandelate, fumarate, and N-acetylglycine, along with a significantly lower level of oxypurinol compared to PKW. This study seeks to develop the theoretical understanding of the fermentation of kiwifruit with peel in sight of the utilization of the whole fruit for KW production, to increase the economic value of kiwifruit production.

Preparation and characterization of fennel (Foeniculum vulgare miller) essential oil/hydroxypropyl-ß-cyclodextrin inclusion complex and its application for chilled pork preservation.

Fennel essential oil (FEO) a natural spice that has versatile biological activities. However, the direct use of FEO is limited due to its water insolubility and poor stability. Chilled pork is prone to spoilage during storage. To solve these problems, this study aimed to prepare an inclusion complex (IC) of FEO with hydroxypropyl-ß-cyclodextrin via co-precipitation and apply it to the preservation of chilled pork. Results indicated that the optimal parameters were encapsulating temperature 37 °C, wall-core ratio 14:1 g/mL, stirring speed 600 r/min, and encapsulating time 240 min, obtaining an encapsulation efficiency of 83.75%. The results of scanning electron microscopy, Fourier transform infra-red spectroscopy, and nuclear magnetic resonance demonstrated the successful preparation of IC. The release of FEO from IC was controllable through adjusting the different temperatures and relative humidities. Furthermore, IC effectively delayed the spoilage of chilled pork and extended its shelf life by 6 days at 4 °C.

Proteomics Analysis of Interactions between Drug-Resistant and Drug-Sensitive Cancer Cells: Comparative Studies of Monoculture and Coculture Cell Systems.

Cell-cell interactions, which allow cells to communicate with each other through molecules in their microenvironment, are critical for the growth, health, and functions of cells. Previous studies show that drug-resistant cells can interact with drug-sensitive cells to elevate their drug resistance level, which is partially responsible for cancer recurrence. Studying protein targets and pathways involved in cell-cell communication provides essential information for fundamental cell biology studies and therapeutics of human diseases. In the current studies, we performed direct coculture and indirect coculture of drug-resistant and drug-sensitive cell lines, aiming to investigate intracellular proteins responsible for cell communication. Comparative studies were carried out using monoculture cells. Shotgun bottom-up proteomics results indicate that the P53 signaling pathway has a strong association with drug resistance mechanisms, and multiple TP53-related proteins were upregulated in both direct and indirect coculture systems. In addition, cell-cell communication pathways, including the phagosome and the HIF-signaling pathway, contribute to both direct and indirect coculture systems. Consequently, AK3 and H3-3A proteins were identified as potential targets for cell-cell interactions that are relevant to drug resistance mechanisms. We propose that the P53 signaling pathway, in which mitochondrial proteins play an important role, is responsible for inducing drug resistance through communication between drug-resistant and drug-sensitive cancer cells.

Comparative Seed Proteome Profile Reveals No Alternation of Major Allergens in High-Yielding Mung Bean Cultivars.

Mung bean contains up to 32.6% protein and is one of the great sources of plant-based protein. Because many allergens also function as defense-related proteins, it is important to determine their abundance levels in the high-yielding, disease-resistant cultivars. In this study, for the first time, we compared the seed proteome of high-yielding mung bean cultivars developed by a conventional breeding approach. Using a label-free quantitative proteomic platform, we successfully identified and quantified a total of 1373 proteins. Comparative analysis between the high-yielding disease-resistant cultivar (MC5) and the other three cultivars showed that a total of 69 common proteins were significantly altered in their abundances across all cultivars. Bioinformatic analysis of these altered proteins demonstrated that PDF1 (a defensin-like protein) exhibited high sequence similarity and epitope matching with the established peanut allergens, indicating a potential mung bean allergen that showed a cultivar-specific response. Conversely, known mung bean allergen proteins such as PR-2/PR-10 (Vig r 1), Vig r 2, Vig r 4, LTP1, ß-conglycinin, and glycinin G4 showed no alternation in the MC5 compared to other cultivars. Taken together, our findings suggest that the known allergen profiles may not be impacted by the conventional plant breeding method to develop improved mung bean cultivars.

Microbiome and metabolome analyses of milk and feces from dairy cows with healthy, subclinical, and clinical mastitis.

Mastitis is commonly recognized as a localized inflammatory udder disease induced by the infiltration of exogenous pathogens. In the present study, our objective was to discern fecal and milk variations in both microbiota composition and metabolite profiles among three distinct groups of cows: healthy cows, cows with subclinical mastitis and cows with clinical mastitis. The fecal microbial community of cows with clinical mastitis was significantly less rich and diverse than the one harbored by healthy cows. In parallel, mastitis caused a strong disturbance in milk microbiota. Metabolomic profiles showed that eleven and twenty-eight molecules exhibited significant differences among the three groups in feces and milk, respectively. Similarly, to microbiota profile, milk metabolome was affected by mastitis more extensively than fecal metabolome, with particular reference to amino acids and sugars. Pathway analysis revealed that amino acids metabolism and energy metabolism could be considered as the main pathways altered by mastitis. These findings underscore the notable distinctions of fecal and milk samples among groups, from microbiome and metabolomic points of view. This observation stands to enhance our comprehension of mastitis in dairy cows.

Cuproptosis: unveiling a new frontier in cancer biology and therapeutics.

Copper plays vital roles in numerous cellular processes and its imbalance can lead to oxidative stress and dysfunction. Recent research has unveiled a unique form of copper-induced cell death, termed cuproptosis, which differs from known cell death mechanisms. This process involves the interaction of copper with lipoylated tricarboxylic acid cycle enzymes, causing protein aggregation and cell death. Recently, a growing number of studies have explored the link between cuproptosis and cancer development. This review comprehensively examines the systemic and cellular metabolism of copper, including tumor-related signaling pathways influenced by copper. It delves into the discovery and mechanisms of cuproptosis and its connection to various cancers. Additionally, the review suggests potential cancer treatments using copper ionophores that induce cuproptosis, in combination with small molecule drugs, for precision therapy in specific cancer types.

The host sex contributes to the endophytic bacterial community in Sargassum thunbergii and their receptacles.

Endophytic bacteria have a complex coevolutionary relationship with their host macroalgae. Dioecious macroalgae are important producers in marine ecosystems, but there is still a lack of research on how sex influences their endophytic bacteria. In this study, the endophytic bacterial communities in male and female S. thunbergii and their reproductive tissues (receptacles) were compared using culture methods and high-throughput sequencing. The endophytic bacterial communities detected by the two methods were different. Among the 78 isolated strains, the dominant phylum, genus, and species were Bacillota, Alkalihalobacillus, and Alkalihalobacillus algicola, respectively, in the algal bodies, while in the receptacles, they were Bacillota, Vibrio, and Vibrio alginolyticus. However, 24 phyla and 349 genera of endophytic bacteria were identified by high-throughput sequencing, and the dominant phylum and genus were Pseudomonadota and Sva0996_ Marine_ Group, respectively, in both the algal body and the receptacles. The two methods showed similar compositions of endophytic bacterial communities between the samples of different sexes, but the relative abundances of dominant and specific taxa were different. The high-throughput sequencing results showed more clearly that the sex of the host alga had an effect on its endophyte community assembly and a greater effect on the endophytic bacterial community in the receptacles. Moreover, most specific bacteria and predicted functional genes that differed between the samples from the males and females were related to metabolism, suggesting that metabolic differences are the main causes of sex differences in the endophytic bacterial community. Our research is the first to show that host sex contributes to the composition of endophytic bacterial communities in dioecious marine macroalgae. The results enrich the database of endophytic bacteria of dioecious marine macroalgae and pave the way for better understanding the assembly mechanism of the endophytic bacterial community of algae.

Urine proteome profile of firefighters with exposure to emergency fire-induced smoke: A pilot study to identify potential carcinogenic effects.

Firefighters are frequently exposed to a variety of chemicals formed from smoke, which pose a risk for numerous diseases, including cancer. Comparative urine proteome profiling could significantly improve our understanding of the early detection of potential cancer biomarkers. In this study, for the first time, we conducted a comparative protein profile analysis of 20 urine samples collected from ten real-life firefighters prior to and following emergency fire-induced smoke. Using a label-free quantitative proteomics platform, we identified and quantified 1325 unique protein groups, of which 45 proteins showed differential expressions in abundance in response to fire-smoke exposure (post) compared to the control (pre). Pathway analysis showed proteins associated with epithelium development (e.g., RHCG, HEG1, ADAMTSL2) and Alzheimer's disease (SORL1) were significantly increased in response to smoke exposure samples. A protein-protein-network study showed a possible link between these differentially abundant proteins and the known cancer gene (TP53). Moreover, a cross-comparison analysis revealed that seven proteins-ALDH1A1, APCS, POMC, COL2A1, RDX, DDAH2, and SDC4 overlapped with the previously published urine cancer proteome datasets, suggesting a potential cancer risk. Our findings demonstrated that the discovery proteomic platform is a promising analytical technique for identifying potential non-invasive biomarkers associated with fire-smoke exposure in firefighters that may be related to cancer.

Community structure of endophytic bacteria of Sargassum thubergii in the intertidal zone of Qingdao in China.

Endophytic bacteria are one of the symbiotic microbial groups closely related to host algae. However, less research on the endophytic bacteria of marine algae. In this study, the endophytic bacterial community of Sargassum thunbergii was investigated using the culture method and high-throughput sequencing. Thirty-nine endophytic bacterial strains, belonging to two phyla, five genera and sixteen species, were isolated, and Firmicutes, Bacillus and Metabacillus indicus were the dominant taxa at the phylum, genus and species level, respectively. High-throughput sequencing revealed 39 phyla and 574 genera of endophytic bacteria, and the dominant phylum was Proteobacteria, while the dominant genus was Ralstonia. The results also indicated that the endophytic bacteria of S. thunbergii included various groups with nitrogen fixation, salt tolerance, pollutant degradation, and antibacterial properties but also contained some pathogenic bacteria. Additionally, the endophytic bacterial community shared a large number of groups with the epiphytic bacteria and bacteria in the surrounding seawater, but the three groups of samples could be clustered separately. In conclusion, there are a variety of functional endophytic bacteria living in S. thunbergii, and the internal condition of algae is a selective factor for the formation of endophytic bacterial communities. This study enriched the database of endophytic bacteria in marine macroalgae, paving the way for further understanding of the interrelationships between endophytic bacteria, macroalgae, and the environment.

Dendrobium officinale Polysaccharide (DOP) inhibits cell hyperproliferation, inflammation and oxidative stress to improve keratinocyte psoriasis-like state.

PURPOSE: Psoriasis is a skin disease characterized by excessive proliferation, inflammation and oxidative stress in keratinocytes. The present study aimed to investigate the therapeutic effects of Dendrobium officinale polysaccharide (DOP) on keratinocyte psoriasis-like models. METHODS: The HaCaT keratinocyte inflammation models were induced by interleukin (IL)-22 or lipopolysaccharide (LPS), respectively, and oxidative stress damage within cells was elicited by H2O2 and treated using DOP. CCK-8 and EdU were carried out to detect cell proliferation. ELISA, qRT-PCR, and Western blot were conducted to measure the expression of pro-inflammatory cytokines IL17A, IL-23, IL1ß, tumor necrosis factor alpha (TNF-α), and IL-6. Reactive oxygen species (ROS) level in keratinocytes was detected by flow cytometry. Cell proliferation-associated proteins (PCNA, Ki67, Cyclin D1) and pathway proteins (p-AKT and AKT), and oxidative stress marker proteins (Nrf-2, CAT, SOD1) were detected by Western blot. RESULT: DOP did not affect the proliferation of normal keratinocytes, but DOP was able to inhibit the proliferative activity of IL-22-induced overproliferating keratinocytes and suppress the expression of proliferation-related factors PCNA, Ki67, and Cyclin D1 as well as the proliferation pathway p-AKT. In addition, DOP treatment was able to inhibit IL-22 and LPS-induced inflammation and H2O2-induced oxidative stress, including the expression of IL17A, IL-23, IL1ß, TNF-α, IL-6, and IL1ß, as well as the expression levels of intracellular ROS levels and cellular oxidative stress-related indicators SOD, MDA, CAT, Nrf-2 and SOD1. CONCLUSION: DOP inhibits keratinocyte hyperproliferation, inflammation and oxidative stress to improve the keratinocyte psoriasis-like state.

CAR T treatment beyond cancer: Hope for immunomodulatory therapy of non-cancerous diseases.

Engineering a patient's own T cells to accurately identify and eliminate cancer cells has effectively cured individuals afflicted with previously incurable hematologic cancers. These findings have stimulated research into employing chimeric antigen receptor (CAR) T therapy across various areas within the field of oncology. However, evidence from both clinical and preclinical investigations emphasize the broader potential of CAR T therapy, extending beyond oncology to address autoimmune disorders, persistent infections, cardiac fibrosis, age-related ailments and other conditions. Concurrently, the advent of novel technologies and platforms presents additional avenues for utilizing CAR T therapy in non-cancerous contexts. This review provides an overview of the rationale behind CAR T therapy, delineates ongoing challenges in its application to cancer treatment, summarizes recent findings in non-cancerous diseases, and engages in discourse regarding emerging technologies that bear relevance. The review delves into prospective applications of this therapeutic approach across a diverse range of scenarios. Lastly, the review underscores concerns related to precision and safety, while also outlining the envisioned trajectory for extending CAR T therapy beyond cancer treatment.

Adsorption and activation of small molecules on boron nitride catalysts.

Hexagonal boron nitride possesses a unique layered structure, high specific surface area and similar electronic properties as graphene, which makes it not only a promising catalyst support, but also a highly effective metal-free catalyst in the booming field of green chemistry. Reactions involving small molecules (e.g., oxygen, low carbon alkanes, nitrogen and carbon dioxide) have always been a hot topic in catalytic research, especially associated with the adsorption and activation regime of different forms of small molecules on catalysts. In this review, we have investigated the adsorption of different small molecules and the relevant activation mechanisms of four typical chemical bonds (OO, C-H, NN, CO) on hexagonal boron nitride. Recent progress on approaches adopted to enhance the activation capacity such as doping, defect engineering and heterostructuring are summarized, highlighting the potential applications of nonmetallic hexagonal boron nitride catalysts in various reactions. This comprehensive investigation offers a reference point for the enhanced mechanistic understanding and future design of effective and sustainable catalytic systems based on boron nitride.

On-Substrate Fabrication of CsPbBr3 Single-Crystal Microstructures via Nanoparticle Self-Assembly-Assisted Low-Temperature Sintering.

The growth of all-inorganic perovskite single-crystal microstructures on substrates is a promising approach for constructing photonic and electronic microdevices. However, current preparation methods typically involve direct control of ions or atoms, which often depends on specific lattice-matched substrates for epitaxial growth and other stringent conditions that limit the mild preparation and flexibility of device integration. Herein, we present the on-substrate fabrication of CsPbBr3 single-crystal microstructures obtained via a nanoparticle self-assembly assisted low-temperature sintering (NSALS) method. Sintering guided by self-assembled atomically oriented superlattice embryos facilitated the formation of single-crystal microstructures under mild conditions without substrate dependence. The as-prepared on-substrate microstructures exhibited a consistent out-of-plane orientation with a carrier lifetime of up to 82.7 ns. Photodetectors fabricated by using these microstructures exhibited an excellent photoresponse of 9.15 A/W, and the dynamic optical response had a relative standard deviation as low as 0.1831%. The discrete photosensor microarray chip with 174000 pixels in a 100 mm2 area showed a response difference of less than 6%. This method of nanoscale particle-controlled single crystal growth on a substrate offers a perspective for mild-condition preparation and in situ repair of crystals of various types. This advancement can propel the flexible integration and widespread application of perovskite devices.