Single Cell Atlas: a single-cell multi-omics human cell encyclopedia.

Single-cell sequencing datasets are key in biology and medicine for unraveling insights into heterogeneous cell populations with unprecedented resolution. Here, we construct a single-cell multi-omics map of human tissues through in-depth characterizations of datasets from five single-cell omics, spatial transcriptomics, and two bulk omics across 125 healthy adult and fetal tissues. We construct its complement web-based platform, the Single Cell Atlas (SCA, www.singlecellatlas.org ), to enable vast interactive data exploration of deep multi-omics signatures across human fetal and adult tissues. The atlas resources and database queries aspire to serve as a one-stop, comprehensive, and time-effective resource for various omics studies.

Dorsal CA3 overactivation mediates witnessing stress-induced recognition memory deficits in adolescent male mice.

Witnessing violent or traumatic events is common during childhood and adolescence and could cause detrimental effects such as increased risks of psychiatric disorders. This stressor could be modeled in adolescent laboratory animals using the chronic witnessing social defeat (CWSD) paradigm, but the behavioral consequences of CWSD in adolescent animals remain to be validated for cognitive, anxiety-like, and depression-like behaviors and, more importantly, the underlying neural mechanisms remain to be uncovered. In this study, we first established the CWSD model in adolescent male mice and found that CWSD impaired cognitive function and increased anxiety levels and that these behavioral deficits persisted into adulthood. Based on the dorsal-ventral functional division in hippocampus, we employed immediate early gene c-fos immunostaining after behavioral tasks and found that CWSD-induced cognition deficits were associated with dorsal CA3 overactivation and anxiety-like behaviors were associated with ventral CA3 activity reduction. Indeed, chemogenetic activation and inhibition of dorsal CA3 neurons mimicked and reversed CWSD-induced recognition memory deficits (not anxiety-like behaviors), respectively, whereas both inhibition and activation of ventral CA3 neurons increased anxiety-like behaviors in adolescent mice. Finally, chronic administration of vortioxetine (a novel multimodal antidepressant) successfully restored the overactivation of dorsal CA3 neurons and the cognitive deficits in CWSD mice. Together, our findings suggest that dorsal CA3 overactivation mediates CWSD-induced recognition memory deficits in adolescent male mice, shedding light on the pathophysiology of adolescent CWSD-induced adverse effects and providing preclinical evidence for early treatment of stress-induced cognitive deficits.

Fluoxetine reverses early-life stress-induced depressive-like behaviors and region-specific alterations of monoamine transporters in female mice.

The sex difference that females are more vulnerable to depression than males has been recently replicated in an animal model of early-life stress (ES) called the limited bedding and nesting material (LBN) paradigm. Adopting this animal model, we have previously examined the effects of ES on monoamine transporter (MATs) expression in stress-related regions in adult female mice, and the reversal effects of a novel multimodal antidepressant, vortioxetine. In this study, replacing vortioxetine with a classical antidepressant, fluoxetine, we aimed to replicate the ES effects in adult female mice and to elucidate the commonality and differences between fluoxetine and vortioxetine. We found that systemic 30-day treatment with fluoxetine successfully reversed ES-induced depression-like behaviors (especially sucrose preference) in adult female mice. At the molecular level, we largely replicated the ES effects, such as reduced serotonin transporter (SERT) expression in the amygdala and increased norepinephrine transporter (NET) expression in the medial prefrontal cortex (mPFC) and hippocampus. Similar reversal effects of fluoxetine and vortioxetine were observed, including SERT in the amygdala and NET in the mPFC, whereas different reversal effects were observed for NET in the hippocampus and vesicular monoamine transporters expression in the nucleus accumbens. Overall, these results demonstrate the validity of the LBN paradigm to induce depression-like behaviors in female mice, highlight the involvement of region-specific MATs in ES-induced depression-like behaviors, and provide insights for further investigation of neurobiological mechanisms, treatment, and prevention associated with depression in women.

Modulator of TMB-associated immune infiltration (MOTIF) predicts immunotherapy response and guides combination therapy.

Patients with high tumor mutational burden (TMB) levels do not consistently respond to immune checkpoint inhibitors (ICIs), possibly because a high TMB level does not necessarily result in adequate infiltration of CD8+ T cells. Using bulk ribonucleic acid sequencing (RNA-seq) data from 9311 tumor samples across 30 cancer types, we developed a novel tool called the modulator of TMB-associated immune infiltration (MOTIF), which comprises genes that can determine the extent of CD8+ T cell infiltration prompted by a certain TMB level. We confirmed that MOTIF can accurately reflect the integrity and defects of the cancer-immunity cycle. By analyzing 84 human single-cell RNA-seq datasets from 32 types of solid tumors, we revealed that MOTIF can provide insights into the diverse roles of various cell types in the modulation of CD8+ T cell infiltration. Using pretreatment RNA-seq data from 13 ICI-treated cohorts, we validated the use of MOTIF in predicting CD8+ T cell infiltration and ICI efficacy. Among the components of MOTIF, we identified EMC3 as a negative regulator of CD8+ T cell infiltration, which was validated via in vivo studies. Additionally, MOTIF provided guidance for the potential combinations of programmed death 1 blockade with certain immunostimulatory drugs to facilitate CD8+ T cell infiltration and improve ICI efficacy.

Vitamin K1 ameliorates lipopolysaccharide-triggered skeletal muscle damage revealed by faecal bacteria transplantation.

BACKGROUND: Sepsis-associated muscle weakness is common in patients of intensive care units (ICUs), and it is closely associated with poor outcomes. The mechanism of sepsis-induced muscle weakness is unclear. Recent studies have found that gut microbiota and metabolites are involved in the regulation of skeletal muscle mass and metabolism. This study aimed to investigate the effects of gut microbiota and metabolites on sepsis-associated muscle weakness. METHODS: In a lipopolysaccharide (LPS)-induced inflammation mouse model, mice with different sensitivities to LPS-induced inflammation were considered as donor mice for the faecal microbiota transplantation (FMT) assay, and recipient mice were divided into sensitive (Sen) and resistant (Res) groups. Skeletal muscle mass and function, as well as colonic barrier integrity were tested and gut microbiota and metabolite composition were analysed in both groups of mice. The effect of intestinal differential metabolite vitamin K1 on LPS-triggered muscle damage was investigated, and the underlying mechanism was explored. RESULTS: Recipients exhibited varying LPS-triggered muscle damage and intestinal barrier disruption. Tibialis anterior (TA) muscle of Sen exhibited upregulated expression levels of MuRF-1 (0.825 ± 0.063 vs. 0.304 ± 0.293, P = 0.0141) and MAFbx (1.055 ± 0.079 vs. 0.456 ± 0.3, P = 0.0092). Colonic tight junction proteins ZO-1 (0.550 ± 0.087 vs. 0.842 ± 0.094, P = 0.0492) and occludin (0.284 ± 0.057 vs. 0.664 ± 0.191, P = 0.0487) were significantly downregulated in the Sen group. Metabolomic analysis showed significantly higher vitamin K1 in the faeces (P = 0.0195) and serum of the Res group (P = 0.0079) than those of the Sen group. After vitamin K1 intervention, muscle atrophy-related protein expression downregulated (P < 0.05). Meanwhile SIRT1 protein expression were upregulated (0.320 ± 0.035 vs. 0.685 ± 0.081, P = 0.0281) and pNF-κB protein expression were downregulated (0.815 ± 0.295 vs. 0.258 ± 0.130, P = 0.0308). PI3K (0.365 ± 0.142 vs. 0.763 ± 0.013, P = 0.0475), pAKT (0.493 ± 0.159 vs. 1.183 ± 0.344, P = 0.0254) and pmTOR (0.509 ± 0.088 vs. 1.110 ± 0.190, P = 0.0368) protein expression levels were upregulated in TA muscle. Meanwhile, vitamin K1 attenuated serum inflammatory factor levels. CONCLUSIONS: Vitamin K1 might ameliorate LPS-triggered skeletal muscle damage by antagonizing NF-κB-mediated inflammation through upregulation of SIRT1 and regulating the balance between protein synthesis and catabolism.

Ursa: A Comprehensive Multiomics Toolbox for High-Throughput Single-Cell Analysis.

The burgeoning amount of single-cell data has been accompanied by revolutionary changes to computational methods to map, quantify, and analyze the outputs of these cutting-edge technologies. Many are still unable to reap the benefits of these advancements due to the lack of bioinformatics expertise. To address this issue, we present Ursa, an automated single-cell multiomics R package containing 6 automated single-cell omics and spatial transcriptomics workflows. Ursa allows scientists to carry out post-quantification single or multiomics analyses in genomics, transcriptomics, epigenetics, proteomics, and immunomics at the single-cell level. It serves as a 1-stop analytic solution by providing users with outcomes to quality control assessments, multidimensional analyses such as dimension reduction and clustering, and extended analyses such as pseudotime trajectory and gene-set enrichment analyses. Ursa aims bridge the gap between those with bioinformatics expertise and those without by providing an easy-to-use bioinformatics package for scientists in hoping to accelerate their research potential. Ursa is freely available at https://github.com/singlecellomics/ursa.

SEPSIS LEADS TO IMPAIRED MITOCHONDRIAL CALCIUM UPTAKE AND SKELETAL MUSCLE WEAKNESS BY REDUCING THE MICU1:MCU PROTEIN RATIO.

ABSTRACT: Purpose: Intensive care unit-acquired weakness (ICUAW) is a severe neuromuscular complication that frequently occurs in patients with sepsis. The precise molecular pathophysiology of mitochondrial calcium uptake 1 (MICU1) and mitochondrial calcium uniporter (MCU) in ICUAW has not been fully elucidated. Here, we speculate that ICUAW is associated with MICU1:MCU protein ratio-mediated mitochondrial calcium ([Ca 2+ ] m ) uptake dysfunction. Methods: Cecal ligation and perforation (CLP) was performed on C57BL/6J mice to induce sepsis. Sham-operated animals were used as controls. Lipopolysaccharide (LPS) (5 µg/mL) was used to induce inflammation in differentiated C2C12 myoblasts. Compound muscle action potential (CMAP) was detected using a biological signal acquisition system. Grip strength was measured using a grip-strength meter. Skeletal muscle inflammatory factors were detected using ELISA kits. The cross-sectional area (CSA) of the tibialis anterior (TA) muscle was detected by hematoxylin and eosin staining. Cytosolic calcium ([Ca 2+ ] c ) levels were measured using Fluo-4 AM. Adeno-associated virus (AAV) was injected into TA muscles for 4 weeks to overexpress MICU1 prophylactically. A lentivirus was used to infect C2C12 cells to increase MICU1 expression prophylactically. Findings: The results suggest that sepsis induces [Ca 2+ ] m uptake disorder by reducing the MICU1:MCU protein ratio, resulting in skeletal muscle weakness and muscle fiber atrophy. However, MICU1 prophylactic overexpression reversed these effects by increasing the MICU1:MCU protein ratio. Conclusions: ICUAW is associated with impaired [Ca 2+ ] m uptake caused by a decreased MICU1:MCU protein ratio. MICU1 overexpression improves sepsis-induced skeletal muscle weakness and atrophy by ameliorating the [Ca 2+ ] m uptake disorder.

mRNA vaccine in cancer therapy: Current advance and future outlook.

Messenger ribonucleic acid (mRNA) vaccines are a relatively new class of vaccines that have shown great promise in the immunotherapy of a wide variety of infectious diseases and cancer. In the past 2 years, SARS-CoV-2 mRNA vaccines have contributed tremendously against SARS-CoV2, which has prompted the arrival of the mRNA vaccine research boom, especially in the research of cancer vaccines. Compared with conventional cancer vaccines, mRNA vaccines have significant advantages, including efficient production of protective immune responses, relatively low side effects and lower cost of acquisition. In this review, we elaborated on the development of cancer vaccines and mRNA cancer vaccines, as well as the potential biological mechanisms of mRNA cancer vaccines and the latest progress in various tumour treatments, and discussed the challenges and future directions for the field.

Ce-mediated molecular tailoring on gigantic polyoxometalate {Mo132} into half-closed {Ce11Mo96} for high proton conduction.

Precise synthesis of polyoxometalates (POMs) is important for the fundamental understanding of the relationship between the structure and function of each building motif. However, it is a great challenge to realize the atomic-level tailoring of specific sites in POMs without altering the major framework. Herein, we report the case of Ce-mediated molecular tailoring on gigantic {Mo132}, which has a closed structural motif involving a never seen {Mo110} decamer. Such capped wheel {Mo132} undergoes a quasi-isomerism with known {Mo132} ball displaying different optical behaviors. Experiencing an 'Inner-On-Outer' binding process with the substituent of {Mo2} reactive sites in {Mo132}, the site-specific Ce ions drive the dissociation of {Mo2*} clipping sites and finally give rise to a predictable half-closed product {Ce11Mo96}. By virtue of the tailor-made open cavity, the {Ce11Mo96} achieves high proton conduction, nearly two orders of magnitude than that of {Mo132}. This work offers a significant step toward the controllable assembly of POM clusters through a Ce-mediated molecular tailoring process for desirable properties.

Impact of Social Interaction on Customer Engagement in China's Social Commerce-A Moderated Chain Mediation Model.

With the emergence of social commerce, customer engagement is increasingly considered as an important influencing factor for enterprises to maintain a competitive advantage. Despite the extensive literature examining the determinants of customer engagement in social commerce from the perspectives of platform functions and technical dimensions, discussions on social interaction remain rare. Based on a sample dataset of 460 valid questionnaires collected via an online survey within China, using the structural equation model, this study attempts to investigate the effect of social interaction on customer engagement. Specifically, it divides social interaction into two dimensions, namely information-oriented and relation-oriented interactions. It is found that both informational and relational interactions are essential for driving customer engagement. Social presence and customer trust sequentially mediate the effect of social interaction to enhance customer engagement. In other words, social interaction enhances the sense of social presence, which in turn heightens customer trust, ultimately spurring a greater customer engagement. Self-construal moderates the relationship between social interaction and customer engagement. For interdependent customers, the effect of social interaction on customer trust is particularly significant. This study provides novel insights into how and when social interaction shapes customer engagement, highlighting the mechanisms and boundary conditions involved in this relationship within a social commerce context, which can also offer practical guidance for platforms and merchants seeking to facilitate greater engagement among customers.

Universal cutoff for tumor mutational burden in predicting the efficacy of anti-PD-(L)1 therapy for advanced cancers.

Background: The US Food and Drug Administration (FDA)'s tumor-agnostic approval of pembrolizumab in high tumor mutational burden (TMB-high, i.e., TMB≥10 mut/Mb) cases, based on the data from KEYNOTE-158, has raised considerable concerns among the immuno-oncology community. This study aims to statistically infer the optimal universal cutoff in defining TMB-high that is predictive of the efficacy of anti-PD-(L) 1 therapy in advanced solid tumors. Methods: We integrated MSK-IMPACT TMB data from a public cohort and the objective response rate (ORR) for anti-PD-(L) 1 monotherapy across diverse cancer types in published trials. The optimal TMB cutoff was determined by varying the universal cutoff to define TMB-high across cancer types and examining the cancer-level correlation between objective response rate and the proportion of TMB-high cases. The utility of this cutoff in predicting overall survival (OS) benefits from anti-PD-(L) 1 therapy was then evaluated in a validation cohort of advanced cancers with coupled MSK-IMPACT TMB and OS data. In silico analysis of whole-exome sequencing data from The Cancer Genome Atlas was further employed to assess the generalizability of the identified cutoff among panels comprising several hundred genes. Results: The cancer type-level analysis identified 10 mut/Mb as the optimal cutoff for MSK-IMPACT in defining TMB-high, with the corresponding TMB-high (TMB≥10 mut/Mb) percentage strongly correlated with ORR for PD-(L) 1 blockade across cancer types [correlation coefficient, 0.72 (95% CI, 0.45-0.88)]. This cutoff was also the optimum in defining TMB-high (via MSK-IMPACT) when predicting OS benefits from anti-PD-(L) 1 therapy in the validation cohort. In this cohort, TMB≥10 mut/Mb was associated with significantly improved OS (hazard ratio, 0.58 [95% CI, 0.48-0.71]; p < 0.001). Moreover, in silico analyses revealed excellent agreement of TMB≥10 mut/Mb cases between MSK-IMPACT and the FDA-approved panels and between MSK-IMPACT and various randomly sampled panels. Conclusion: Our study demonstrates that 10 mut/Mb is the optimal, universal cutoff for TMB-high that guides the clinical application of anti-PD-(L) 1 therapy for advanced solid tumors. It also provides rigorous evidence beyond KEYNOTE-158 for the utility of TMB≥10 mut/Mb in predicting the efficacy of PD-(L) 1 blockade in broader settings, which could help to mitigate the challenges in embracing the tumor-agnostic approval of pembrolizumab in TMB-high cases.

Actionable cancer vulnerability due to translational arrest, p53 aggregation and ribosome biogenesis stress evoked by the disulfiram metabolite CuET.

Drug repurposing is a versatile strategy to improve current therapies. Disulfiram has long been used in the treatment of alcohol dependency and multiple clinical trials to evaluate its clinical value in oncology are ongoing. We have recently reported that the disulfiram metabolite diethyldithiocarbamate, when combined with copper (CuET), targets the NPL4 adapter of the p97VCP segregase to suppress the growth of a spectrum of cancer cell lines and xenograft models in vivo. CuET induces proteotoxic stress and genotoxic effects, however important issues concerning the full range of the CuET-evoked tumor cell phenotypes, their temporal order, and mechanistic basis have remained largely unexplored. Here, we have addressed these outstanding questions and show that in diverse human cancer cell models, CuET causes a very early translational arrest through the integrated stress response (ISR), later followed by features of nucleolar stress. Furthermore, we report that CuET entraps p53 in NPL4-rich aggregates leading to elevated p53 protein and its functional inhibition, consistent with the possibility of CuET-triggered cell death being p53-independent. Our transcriptomics profiling revealed activation of pro-survival adaptive pathways of ribosomal biogenesis (RiBi) and autophagy upon prolonged exposure to CuET, indicating potential feedback responses to CuET treatment. The latter concept was validated here by simultaneous pharmacological inhibition of RiBi and/or autophagy that further enhanced CuET's tumor cytotoxicity, using both cell culture and zebrafish in vivo preclinical models. Overall, these findings expand the mechanistic repertoire of CuET's anti-cancer activity, inform about the temporal order of responses and identify an unorthodox new mechanism of targeting p53. Our results are discussed in light of cancer-associated endogenous stresses as exploitable tumor vulnerabilities and may inspire future clinical applications of CuET in oncology, including combinatorial treatments and focus on potential advantages of using certain validated drug metabolites, rather than old, approved drugs with their, often complex, metabolic profiles.

[Decreased Expression of Mitochondrial Calcium Uptake Protein 1 Leads to Skeletal Muscle Dysfunction in Septic Mice].

Objective: To observe the effect of sepsis on skeletal muscle function and to explore the role of skeletal muscle mitochondrial calcium uptake protein 1 (MICU1). Methods: A total of 40 specific-pathogen-free (SPF) healthy male C57BL/6J mice were randomly assigned to 4 groups, a sham operation group (Sham group, n=8), a sepsis modeling 6 h group (cecal ligation and puncture [CLP]-6 h group, n=10), a sepsis modeling 12 h group (CLP-12 h group, n=10), and a sepsis modeling 24 h group (CLP-24 h, n=12). The sepsis model was established by CLP. Mice in the Sham group only underwent laparotomic exploration of the cecum. Another 20 SPF mice were selected. The tibialis anterior muscle on one side was empty-transfected with adeno-associated virus (AAV) as controls (AAV-C), and the tibialis anterior muscle on the other side was transfected with AAV to enhance MICU1 expression (AAV-M). The mice were randomly assigned to two groups, a sham operation group (AAV-C-Sham and AAV-M-Sham, n=8) and a sepsis model 24 h group (AAV-C-CLP and AAV-M-CLP, n=12). The grip strength and compound muscle action potential (CMAP) of the tibialis anterior muscle were measured in each group at the corresponding time points. The levels of inflammatory factors, including tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6), in the skeletal muscle were measured by ELISA. The morphological changes of skeletal muscle cells were observed through H&E staining. The expression levels of MICU1 and muscle atrophy-related proteins, including muscle RING-finger containing protein 1 (MuRF1) and muscle atrophy Fbox protein (MAFbx), were determined by Western blot. The expression levels of MICU1 mRNA in skeletal muscle were determined by RT-qPCR. Results: Compared with mice in the Sham group, mice in the CLP group showed decreased body weight ( P<0.05); their grip strength decreased with the prolongation of CLP modeling time ( P<0.05); the amplitude of CMAP decreased, showing prolonged duration and latency ( P<0.05); the expression levels of inflammatory factors, including TNF-α and IL-6, in skeletal muscle increased gradually ( P<0.05); the fiber diameter and cross-sectional area of skeletal muscle decreased gradually with the prolongation of modeling time ( P<0.05); the protein expression levels of MuRF1and MAFbx proteins increased gradually ( P<0.05); the expression levels of MICU1 protein and mRNA decreased gradually ( P<0.05). There was no significant difference in all indices between AAV-M-Sham and AAV-C-Sham groups ( P>0.05). Compared with mice in the AAV-C-CLP group, mice in the AAV-M-CLP group showed increased grip strength ( P<0.05); the amplitude of CMAP increased, showing shortened duration and latency ( P <0.05); the fiber diameter and cross-sectional area of skeletal muscle increased ( P<0.05); the expression levels of MuRF1and MAFbx decreased ( P<0.05). Conclusion: Sepsis leads to skeletal muscle dysfunction, which is related to the decrease in mitochondrial MICU1 expression.

The causal involvement of the BDNF-TrkB pathway in dentate gyrus in early-life stress-induced cognitive deficits in male mice.

Cognitive dysfunction is a significant, untreated clinical need in patients with psychiatric disorders, for which preclinical studies are needed to understand the underlying mechanisms and to identify potential therapeutic targets. Early-life stress (ELS) leads to long-lasting deficits of hippocampus-dependent learning and memory in adult mice, which may be associated with the hypofunction of the brain-derived neurotrophic factor (BDNF) and its high-affinity receptor, tropomyosin receptor kinase B (TrkB). In this study, we carried out eight experiments using male mice to examine the causal involvement of the BDNF-TrkB pathway in dentate gyrus (DG) and the therapeutic effects of the TrkB agonist (7,8-DHF) in ELS-induced cognitive deficits. Adopting the limited nesting and bedding material paradigm, we first demonstrated that ELS impaired spatial memory, suppressed BDNF expression and neurogenesis in the DG in adult mice. Downregulating BDNF expression (conditional BDNF knockdown) or inhibition of the TrkB receptor (using its antagonist ANA-12) in the DG mimicked the cognitive deficits of ELS. Acute upregulation of BDNF (exogenous human recombinant BDNF microinjection) levels or activation of TrkB receptor (using its agonist, 7,8-DHF) in the DG restored ELS-induced spatial memory loss. Finally, acute and subchronic systemic administration of 7,8-DHF successfully restored spatial memory loss in stressed mice. Subchronic 7,8-DHF treatment also reversed ELS-induced neurogenesis reduction. Our findings highlight BDNF-TrkB system as the molecular target of ELS-induced spatial memory deficits and provide translational evidence for the intervention at this system in the treatment of cognitive deficits in stress-related psychiatric disorders, such as major depressive disorder.

Outdoor particulate matter exposure affects metabolome in chronic obstructive pulmonary disease: Preliminary study.

Introduction: The metabolomic changes caused by airborne fine particulate matter (PM2.5) exposure in patients with chronic obstructive pulmonary disease (COPD) remain unclear. The aim of this study was to determine whether it is possible to predict PM2.5-induced acute exacerbation of COPD (AECOPD) using metabolic markers. Methods: Thirty-eight patients with COPD diagnosed by the 2018 Global Initiative for Obstructive Lung Disease were selected and divided into high exposure and low exposure groups. Questionnaire data, clinical data, and peripheral blood data were collected from the patients. Targeted metabolomics using liquid chromatography-tandem mass spectrometry was performed on the plasma samples to investigate the metabolic differences between the two groups and its correlation with the risk of acute exacerbation. Results: Metabolomic analysis identified 311 metabolites in the plasma of patients with COPD, among which 21 metabolites showed significant changes between the two groups, involving seven pathways, including glycerophospholipid, alanine, aspartate, and glutamate metabolism. Among the 21 metabolites, arginine and glycochenodeoxycholic acid were positively associated with AECOPD during the three months of follow-up, with an area under the curve of 72.50% and 67.14%, respectively. Discussion: PM2.5 exposure can lead to changes in multiple metabolic pathways that contribute to the development of AECOPD, and arginine is a bridge between PM2.5 exposure and AECOPD.

Lead zirconate titanate ceramics with aligned crystallite grains.

The piezoelectric properties of lead zirconate titanate [Pb(Zr,Ti)O3 or PZT] ceramics could be enhanced by fabricating textured ceramics that would align the crystal grains along specific orientations. We present a seed-passivated texturing process to fabricate textured PZT ceramics by using newly developed Ba(Zr,Ti)O3 microplatelet templates. This process not only ensures the template-induced grain growth in titanium-rich PZT layers but also facilitates desired composition through interlayer diffusion of zirconium and titanium. We successfully prepared textured PZT ceramics with outstanding properties, including Curie temperatures of 360°C, piezoelectric coefficients d33 of 760 picocoulombs per newton and g33 of 100 millivolt meters per newton, and electromechanical couplings k33 of 0.85. This study addresses the challenge of fabricating textured rhombohedral PZT ceramics by suppressing the otherwise severe chemical reaction between PZT powder and titanate templates.