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Recessive congenital methemoglobinemia (RCM) is a hereditary autosomal disorder with an extremely low incidence rate. Here, we report a case of methemoglobinemia type I in a patient with congenital persistent cyanosis. The condition was attributed to a novel compound heterozygous mutation in CYB5R3, characterized by elevated methemoglobin levels (13.4 % of total hemoglobin) and undetectable NADH cytochrome b5 reductase (CYB5R3) activity. Whole-exome sequencing (WES) revealed two heterozygous mutations in CYB5R3: a previously reported pathogenic missense mutation c.611G>A(p.Cys204Tyr) inherited from the father, and a novel stop codon mutation c.906A>G(p.*302Trpext*42) from the mother, the latter mutation assessed as likely pathogenic according to ACMG guidelines. In cells overexpressing the CYB5R3 c.906A>G mutant construct, the CYB5R3 mRNA level was significantly lower than in cells overexpressing the wild-type (WT) CYB5R3 construct. However, there was no significant difference in protein expression levels between the mutant and WT constructs. Notably, an additional protein band of approximately 55 kDa was detected in the mutant cells. Immunofluorescence localization showed that, compared to wild-type CYB5R3, the subcellular localization of the CYB5R3 p.*302Trpext*42 mutant protein did not show significant changes and remained distributed in the endoplasmic reticulum and mitochondria. However, the c.906A>G(p.*302Trpext*42) mutation resulted in increased intracellular reactive oxygen species (ROS) levels and decreased NAD+/NADH ratio, suggesting impaired CYB5R3 function and implicating this novel mutation as likely pathogenic.

Assuntos

Citocromo-B(5) Redutase , Metemoglobinemia , Mutação , Humanos , Masculino , Códon de Terminação/genética , Citocromo-B(5) Redutase/genética , Citocromo-B(5) Redutase/deficiência , Metemoglobinemia/genética , Metemoglobinemia/congênito , Adulto

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A nonparametric point-by-point (NPP) method is presented for high-accuracy measurement of the time-dependent frequency (laser frequency) in tunable laser absorption spectroscopy, crucial for ensuring ultimate measurement accuracy. In wavelength modulation spectroscopy in particular, the parametric methods in current use for time-dependent frequency measurement are insufficiently accurate and are difficult to apply to complex modulation scenarios. Based on a multi-scale viewpoint, point-by-point measurement of the frequency is realized by linear superposition of the frequency information mapped from the interferometric signal on a unit scale and on a local scale. Validation experiments indicate that the measurement accuracy of the proposed NPP method is three times that of the existing parametric methods, while effectively immunizing against non-ideal tuning effects. Additionally, the NPP method is suitable for use with arbitrarily complex modulations such as square wave modulation, for which parametric methods are inapplicable.

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Inflammation-resident cells within arthritic sites undergo a metabolic shift towards glycolysis, which greatly aggravates rheumatoid arthritis (RA). Reprogramming glucose metabolism can suppress abnormal proliferation and activation of inflammation-related cells without affecting normal cells, holding potential for RA therapy. Single 2-deoxy-d-glucose (2-DG, glycolysis inhibitor) treatment often cause elevated ROS, which is detrimental to RA remission. The rational combination of glycolysis inhibition with anti-inflammatory intervention might cooperatively achieve favorable RA therapy. To improve drug bioavailability and exert synergetic effect, stable co-encapsulation of drugs in long circulation and timely drug release in inflamed milieu is highly desirable. Herein, we designed a stimulus-responsive hyaluronic acid-triglycerol monostearate polymersomes (HTDD) co-delivering 2-DG and dexamethasone (Dex) to arthritic sites. After intravenous injection, HTDD polymersomes facilitated prolonged circulation and preferential distribution in inflamed sites, where overexpressed matrix metalloproteinases and acidic pH triggered drug release. Results indicated 2-DG can inhibit the excessive cell proliferation and activation, and improve Dex bioavailability by reducing Dex efflux. Dex can suppress inflammatory signaling and prevent 2-DG-induced oxidative stress. Thus, the combinational strategy ultimately mitigated RA by inhibiting glycolysis and hindering inflammatory signaling. Our study demonstrated the great potential in RA therapy by reprogramming glucose metabolism in arthritic sites.

Assuntos

Artrite Reumatoide , Desoxiglucose , Dexametasona , Glucose , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/metabolismo , Animais , Glucose/metabolismo , Dexametasona/farmacologia , Dexametasona/uso terapêutico , Camundongos , Desoxiglucose/farmacologia , Inflamação/tratamento farmacológico , Glicólise/efeitos dos fármacos , Polímeros/química , Ácido Hialurônico/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Masculino , Humanos , Proliferação de Células/efeitos dos fármacos

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AIMS: Previous proteomics studies in dysferlinopathy muscle have been limited in scope, often utilizing 2D-electrophoresis and yielding only a small number of differential expression calls. To address this gap, this study aimed to employ high-resolution proteomics to explore the proteomic landscapes of dysferlinopathy and analyze the correlation between muscle pathological changes and alterations in protein expression in muscle biopsies. METHODS: We conducted a comprehensive approach to investigate the proteomic profile and disease-associated changes in the muscle tissue proteome from 15 patients with dysferlinopathy, exhibiting varying degrees of dystrophic pathology, alongside age-matched controls. Our methodology encompasses tandem mass tag (TMT)-labeled liquid chromatography-mass spectrometry (LC-MS/MS)-based proteomics, protein-protein interaction (PPI) network analysis, weighted gene co-expression network analysis, and differential expression analysis. Subsequently, we examined the correlation between the expression of key proteins and the clinical characteristics of the patients to identify pathogenic targets associated with DYSF mutations in dysferlinopathy. RESULTS: A total of 1600 differentially expressed proteins were identified, with 1321 showing high expression levels and 279 expressed at lower levels. Our investigation yields a molecular profile delineating the altered protein networks in dysferlinopathy-afflicted skeletal muscle, uncovering dysregulation across numerous cellular pathways and molecular processes, including mRNA metabolic processes, regulated exocytosis, immune response, muscle system processes, energy metabolic processes, and calcium transmembrane transport. Moreover, we observe significant associations between the protein expression of ANXA1, ANXA2, ANXA4, ANXA5, LMNA, PYGM, and the extent of histopathologic changes in muscle biopsies from patients with dysferlinopathy, validated through immunoblotting and immunofluorescence assays. CONCLUSIONS: Through the aggregation of expression data from dysferlinopathy-impacted muscles exhibiting a range of pathological alterations, we identified multiple key proteins associated with the dystrophic pathology of patients with dysferlinopathy. These findings provide novel insights into the pathogenesis of dysferlinopathy and propose promising targets for future therapeutic endeavors.

Assuntos

Biomarcadores , Progressão da Doença , Músculo Esquelético , Distrofia Muscular do Cíngulo dos Membros , Proteômica , Humanos , Masculino , Distrofia Muscular do Cíngulo dos Membros/patologia , Distrofia Muscular do Cíngulo dos Membros/genética , Distrofia Muscular do Cíngulo dos Membros/metabolismo , Feminino , Adulto , Adulto Jovem , Músculo Esquelético/patologia , Músculo Esquelético/metabolismo , Adolescente , Biomarcadores/metabolismo , Criança , Disferlina/genética , Disferlina/metabolismo , Pessoa de Meia-Idade , Pré-Escolar , Mapas de Interação de Proteínas , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Espectrometria de Massas em Tandem

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The synthetical methodology for the [Cu(dmp)2]2+/1+ (dmp = 2,9-dimethyl-1,10-phenanthroline; neocuproine) complexes has been systematically investigated by using various copper precursors, including CuCl2, Cu(NO3)2, and Cu(ClO4)2. After an anion exchange to trifluoromethanesulfonimide (TFSI), the tetra-coordinated CuII(dmp)2(TFSI)2-Cu(ClO4)2 (7.43%) outperformed the penta-coordinated CuII(dmp)2(TFSI)(NO3)-Cu(NO3)2 (4.30%) and CuII(dmp)2(TFSI)(Cl)-CuCl2. Polymeric chalcogenides, including a conducting copolymeric electrode of PEDOT-PEDTT [PEDOT = poly(3,4-ethylenedioxythiophene); PEDTT = poly(3,4-ethylenedithiothiophene)] and a coordination polymeric electrode of silver bezeneselenolate ([Ag2(SePh)2]n; mithrene), are introduced as the electrocatalysts for [Cu(dmp)2]2+/1+ for the first time. After optimization, dye-sensitized solar cells (DSSCs) based on carbon cloth (CC)/AgSePh-30 (10.18%) showed superior electrocatalytic ability compared to the benchmark CC/Pt (7.43%) due to numerous active sites provided by electron-donating Se atoms, high film roughness, and bottom-up 2D charge transfer routes. The DSSC based on CC/PEDTT-50 (10.38%) also outperformed CC/Pt due to numerous active sites provided by electron-donating S atoms and proper energy band structure. This work sheds light on the future design and synthesis in Cu-complex mediators and functional polymeric chalcogenides for high-performance DSSCs.

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OBJECTIVES: To establish a nomogram for differentiating malignant and benign focal liver lesions (FLLs) using ultrasomics features derived from contrast-enhanced ultrasound (CEUS). METHODS: 527 patients were retrospectively enrolled. On the training cohort, ultrasomics features were extracted from CEUS and b-mode ultrasound (BUS). Automatic feature selection and model development were performed using the Ultrasomics-Platform software, outputting the corresponding ultrasomics scores. A nomogram based on the ultrasomics scores from artery phase (AP), portal venous phase (PVP) and delayed phase (DP) of CEUS, and clinical factors were established. On the validation cohort, the diagnostic performance of the nomogram was assessed and compared with seniorexpert and resident radiologists. RESULTS: In the training cohort, the AP, PVP and DP scores exhibited better differential performance than BUS score, with area under the curve (AUC) of 84.1-85.1% compared with the BUS (74.6%, P < 0.05). In the validation cohort, the AUC of combined nomogram and expert was significantly higher than that of the resident (91.4% vs. 89.5% vs. 79.3%, P < 0.05). The combined nomogram had a comparable sensitivity with the expert and resident (95.2% vs. 98.4% vs. 97.6%), while the expert had a higher specificity than the nomogram and the resident (80.6% vs. 72.2% vs. 61.1%, P = 0.205). CONCLUSIONS: A CEUS ultrasomics based nomogram had an expert level performance in FLL characterization.

Assuntos

Meios de Contraste , Neoplasias Hepáticas , Nomogramas , Ultrassonografia , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Ultrassonografia/métodos , Neoplasias Hepáticas/diagnóstico por imagem , Estudos Retrospectivos , Diagnóstico Diferencial , Adulto , Idoso , Sensibilidade e Especificidade , Fígado/diagnóstico por imagem

RESUMO

BACKGROUND: Previous natural history studies highlighted a consistent heterogeneity of disability trajectories among individuals with primary or secondary progressive multiple sclerosis (MS). However, evidence on disability progression in relapsing onset MS is scarce.The aim of this study was to investigate heterogeneity in disability accumulation over 10 years following a first clinical diagnosis of central nervous system demyelination (FCD) and identify genetic, demographic, environmental and clinical factors associated with these trajectories. METHODS: We used group-based trajectory models to measure heterogeneity in disability trajectories based on the Expanded Disability Status Scale (EDSS) in a prospectively assessed cohort of 263 participants. To capture sustained neurological impairments and avoid issues related to significant changes in EDSS associated with relapse, we did not consider EDSS points recorded within 3 months of a relapse. RESULTS: We identified three distinct and clinically meaningful disability trajectories: No/minimal, moderate and severe. Those in the no/minimal disability trajectory showed no appreciable progression of disability (median EDSS∼1 at 10-year review) while those in the moderate and severe disability trajectories experienced disability worsening (median time to reach EDSS 4 was 9 and 7 years, respectively). Compared with the no/minimal disability trajectory, those with older age, a higher number of relapses within the first 5 years post-FCD, and a higher number of comorbidities at baseline were more likely to be in the worse disability trajectory. Surprisingly, baseline MRI and anatomical site of initial symptoms did not influence long-term outcomes. CONCLUSIONS: Those at higher risk of faster MS disability progression can be identified based on their early clinical characteristics with potential therapeutic implications for early intervention and treatment escalation.

RESUMO

We present the synthesis, structural characterization, and reactivity studies of a tetra-zinc complex supported by the bisphenoxymethanone ligands and its transformation into various di-zinc architectures. Our findings highlight the potential of these complexes in molecular recognition, supramolecular chemistry, and catalysis.

RESUMO

Background: Pancreatic hamartoma, a rare benign non-neoplastic condition, presents challenges in differentiating from other pancreatic diseases due to its atypical imaging and unreliable biopsy results. In this study, we present a case of pancreatic hamartoma and conduct a comprehensive review of relevant literature to outline its characteristic features, aiming to underscore its clinical relevance and implications. Case presentation: A 63-year-old man presented with a pancreatic mass, discovered during evaluation of abdominal pain and distension. Laboratory tests were largely unremarkable. Ultrasound revealed a hypoechoic mass in the head of the pancreas. Subsequent computed tomography and magnetic resonance imaging demonstrated an inhomogeneous mass with a clear boundary in the uncinate process of the pancreas. Furthermore, a distinct delayed enhancement pattern was noted on imaging. Histopathological examination confirmed the diagnosis of pancreatic hamartoma. Conclusions: Preoperative diagnosis of pancreatic hamartoma remains challenging. Imaging modalities can play a crucial role in facilitating accurate diagnosis and potentially avoiding unnecessary surgical intervention in patients with this condition.

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BACKGROUND: In China, nursing information systems (NIS) implementation can face numerous barriers to acceptance, including the attitudes of potential users. However, few studies have evaluated this acceptance. OBJECTIVE: The aim of this study was to explain the acceptance of NIS utilizing a survey based on unified theory of acceptance and use of technology. METHODS: A multi-center cross-sectional study utilizing an online survey was conducted. SPSS AMOS was used to conduct a structural equation modelling analysis. This research followed the STROBE Checklist. RESULTS: A total of 3973 Nurses participated in the study between January 2023 and March 2023. The acceptance of NIS among nurses was overall moderate to high. The proposed model has been rigorously tested and validated using empirical data, ensuring its credibility and dependability. Performance expectancy (PE), social influence (SI), and attitude significantly and positively affected intentions to use NIS. Effort expectancy (EE) did not show any significant effects in the sample. Facilitating conditions (FCs) was found to have a negative relationship with the intention to use NIS. There was a statistically significant difference BI between the different age groups, working years, and computer training experience. The model demonstrates a good fit with the observed data. CONCLUSIONS: This study identified PE, SI, and attitude as facilitators of nurses' intentions to use NIS. The findings about EE indicates that the ease of using NIS does not seem to be a concern among nurses. Moreover, high FC might be perceived as indicative of a complex system or extensive usage, that can lead to increased workload and reduced behavioural intention (BI). The significant differences in BI among various demographic groups highlight the need for more studies understanding the preferences and barriers faced by different, levels of experience and training backgrounds. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

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This study presents the first successful generation of polyclonal antibodies (pAbs) and oligonucleotide aptamers specifically targeting fusaric acid (FA). Utilizing these pAbs and aptamers, three highly sensitive and specific assays were developed for the detection of FA in cereals with limits of detection (LOD) ranging from 5 to 50 ng/g: an antibody-based enzyme-linked immunosorbent assay (ELISA), an aptamer-based enzyme-linked aptamer-sorbent assay (ELASA), and a hybrid enzyme-linked aptamer-antibody sandwich assay (ELAAA). The recovery rates of FA in spiked cereal samples ranged from 87 % to 112 % across all assays. Analysis of 15 cereal feed samples revealed FA contamination levels of 459 to 1743 ng/g (ELISA), 427 to 1960 ng/g (ELASA), and 381 to 1987 ng/g (ELAAA). These results were further validated by HPLC analysis, confirming high consistency within developed assays. Overall, the ELISA, ELASA, and ELAAA are promising tools for the rapid detection of FA, significantly contributing to food safety monitoring.

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In order to address the issue of metering inaccuracies in charging stations that directly affect the development of electric vehicles, a prediction method for the relative error of charging stations based on the ConvFormer model is proposed. The model combines Convolutional Neural Networks (CNN) with Transformer models in parallel, significantly improving the prediction accuracy. First, charging station data is preprocessed using forward interpolation and normalization methods, and the dataset is transformed into a dataset of input relative errors. Then, a neural network with an improved unidirectional convolutional and attention combination for time-series forecasting is constructed, and common regression performance evaluation metrics, MAE (Mean Absolute Error) and MSE (Mean Squared Error), are selected for evaluation. Finally, based on seven days of charging station data, the relative error of charging stations for the next 24 h is predicted, and compared to traditional Transformer and LSTM (Long Short-Term Memory) time-series models. The results show that the improved model yields the lowest values for both MAE and MSE, with a 47.30 % reduction in MAE compared to the Transformer model and a 38.06 % reduction compared to LSTM, and a 66.94 % reduction in MSE compared to the Transformer model and approximately 62.32 % reduction compared to LSTM.

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Parallel single-cell multimodal sequencing is the most intuitive and precise tool for cellular status research. In this study, we propose AMAR-seq to automate methylation, chromatin accessibility, and RNA expression coanalysis with single-cell precision. We validated the accuracy and robustness of AMAR-seq in comparison with standard single-omics methods. The high gene detection rate and genome coverage of AMAR-seq enabled us to establish a genome-wide gene expression regulatory atlas and triple-omics landscape with single base resolution and implement single-cell copy number variation analysis. Applying AMAR-seq to investigate the process of mouse embryonic stem cell differentiation, we revealed the dynamic coupling of the epigenome and transcriptome, which may contribute to unraveling the molecular mechanisms of early embryonic development. Collectively, we propose AMAR-seq for the in-depth and accurate establishment of single-cell multiomics regulatory patterns in a cost-effective, efficient, and automated manner, paving the way for insightful dissection of complex life processes.

RESUMO

C-terminal kinesin motor KIFC1 is increasingly concerned with an essential role in germ cell development. During the spermatogenesis of mice, rats, and crustaceans, KIFC1 functions in regulating meiotic chromosome separation, acrosome vesicle transportation, and nuclear morphology maintenance. The expression pattern of KIFC1 is conservatively concentrated at the acrosome and nucleus of haploid sperm cells. However, whether KIFC1 has similar functions in non-human primates remains unknown. In this study, we constructed the testis-specific cDNA library and cloned different transcripts of KIFC1 based on the genomic sequence. New variants of KIFC1 were identified, and showed different functional domains from the predicted isoforms. The spatio-temporal expression of KIFC1 proteins in seminiferous tubules of rhesus monkeys showed an obvious nuclear localization, specifically expressed in the spermatocytes and early haploid spermatids. The transcripts of KIFC1 also exhibited considerable expression in the nucleus of rhesus LLC-MK2 cells. Besides, we demonstrated that KIFC1 located at the acrosome and microtubule flagella of the mature sperm, and KIFC1 inhibition resulted in sperm tail deformation as well as increased the instability of head-to-tail connection. In summary, this study filled a gap in the reproductive research of the KIFC1 gene in non-human primates.

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PURPOSE: To establish a nomogram for predicting brain metastasis (BM) in primary lung cancer at 12, 18, and 24 months after initial diagnosis. METHODS: In this study, we included 428 patients who were diagnosed with primary lung cancer at Harbin Medical University Cancer Hospital between January 2020 and January 2022. The endpoint event was BM. The patients were randomly categorized into two groups in a 7:3 ratio: training (n = 299) and validation (n = 129) sets. Least absolute shrinkage and selection operator was utilized to analyze the laboratory test results in the training set. Furthermore, clinlabomics-score was determined using regression coefficients. Then, clinlabomics-score was combined with clinical data to construct a nomogram using random survival forest (RSF) and Cox multivariate regression. Then, various methods were used to evaluate the performance of the nomogram. RESULTS: Five independent predictive factors (pathological type, diameter, lymph node metastasis, non-lymph node metastasis and clinlabomics-score) were used to construct the nomogram. In the validation set, the bootstrap C-index was 0.7672 (95% CI 0.7092-0.8037), 12-month AUC was 0.787 (95% CI 0.708-0.865), 18-month AUC was 0.809 (95% CI 0.735-0.884), and 24-month AUC was 0.858 (95% CI 0.792-0.924). In addition, the calibration curve, decision curve analysis and Kaplan-Meier curves revealed a good performance of the nomogram. CONCLUSIONS: Finally, we constructed and validated a nomogram to predict BM risk in primary lung cancer. Our nomogram can identify patients at high risk of BM and provide a reference for clinical decision-making at different disease time points.

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BACKGROUND: Physical activity interventions using habit development may help people increase and then maintain physical activity increases over time. Enacting behavior in consistent contexts is a central component of habit development, yet its causal role in habit development in health behaviors has not been confirmed. PURPOSE: This study tests the causal role of consistent context in habit development in health behavior, using a randomized control trial of a planning intervention to develop a walking habit in 127 insufficiently active, working, midlife adults in a real-world setting. METHODS: We compare participants who plan walking in consistent contexts with controls who plan walking in varied contexts and with controls not required to plan on a change in average daily steps (measured using an accelerometer) and inhabit automaticity during a 4-week intervention and at a 4-week follow-up. RESULTS: As expected, consistent and varied context planners increased walking during the intervention, but only consistent context planners developed (and maintained) habit automaticity. Counter to expectations, consistent context planners did not show walking maintenance. However, across conditions, participants who developed more habit automaticity during the intervention also maintained walking more (decreased less). Having a routine daily schedule moderated some effects. Notably, no-plan controls with greater routine developed more habit automaticity, mediated by walking in more consistent contexts. CONCLUSIONS: This study confirms the causal role of consistent contexts in developing a walking habit, in a real-world setting, with an important but challenging population for physical activity interventions and identifies a facilitating condition common for many: a routine schedule.

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Developing an exercise habit may help people increase and then maintain physical activity. This study tests and confirms the role of exercising in consistent contexts as a cause of forming a daily walking habit. We use a randomized control trial of a 4-week planning intervention, with a follow-up 4 weeks after the intervention. Participants were 127 insufficiently active, working, midlife adults. We compared participants asked to plan their daily walks in consistent contexts from day-to-day, with participants asked to plan their walks in varied contexts and with participants not required to plan. As expected, consistent and varied context planners increased their daily walking steps (measured using an accelerometer) during the intervention compared to participants not required to plan. However, only consistent context planners developed (and then maintained) a daily walking habit, that is, where taking daily walks felt relatively automatic. Unexpectedly, consistent context planners did not show walking maintenance. However, across all participants, those who developed a stronger walking habit during the intervention maintained their walking more after the intervention ended. Lastly, having an existing routine daily schedule helped some participants. Those who were not asked to plan and had a more routine daily schedule also developed a daily walking habit.

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Mental health disparities in transgender and gender diverse (TGD) populations call for more research examining gender minority stressors (GMS) as antecedents to their psychological distress, especially for the long-underrepresented groups living in conservative societies towards gender minorities. Furthermore, some questions remain underexamined, including the relative, independent influences of various GMS on TGD people's mental well-being (i.e., uniqueness of each stressor); how these stressors would configurate with each other in distinctive patterns to characterize subgroups of TGD people (i.e., beyond-average heterogeneity); and how these stressors would constitute a psychological network and vary in their centrality in that network (i.e., holistic complexity). To narrow such gaps, we examined the links between GMS and TGD people's psychological distress, using survey data collected in 2023 from 410 Chinese TGD people (Meanage = 22.33 years, SD = 4.27; 306 transgender, 70 non-binary/gender-queer/gender-fluid, 26 agender/gender-neutral, 3 intersex, and 5 others). We approached such links from three perspectives. First, variable-centered analyses indicated that while different GMS were considered simultaneously, internalized transphobia, preoccupation with gender dysphoria, and gender-related victimization were uniquely associated with psychological distress. Second, person-centered analyses yielded a 3-profile solution. Psychological distress varied systematically across profiles. Last, network analyses revealed a 3-cluster structure: Distal, Proximal Internal, and TGD-Specific Stressors. Preoccupation with gender dysphoria was the most central node. These findings contribute to a more nuanced understanding of the implications of GMS for TGD people's mental well-being. GMS related to internal struggles with gender identity might be among the central intervention targets to prevent/reduce TGD people's psychological distress.

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Spin currents of perpendicularly polarized spins (z spins) have received blooming interest for the potential in energy-efficient spin-orbit torque switching of perpendicular magnetization in the absence of a magnetic field. However, generation of z spins is limited mainly to magnetically or crystallographically low-symmetry single crystals that are hardly compatible with the integration to semiconductor circuits. This work reports efficient generation of z spins in sputter-deposited polycrystalline heavy metal devices via a new mechanism of broken electric symmetries in both the transverse and perpendicular directions. Both the damping-like and field-like spin-orbit torques of z spins can be tuned significantly by varying the degree of the electric asymmetries via the length, width, and thickness of devices as well as by varying the type of the heavy metals. The presence of z spins also enables deterministic, nearly-full, external-magnetic-field-free switching of a uniform perpendicularly magnetized FeCoB layer, the core structure of magnetic tunnel junctions, with high coercivity at a low current density. These results establish the first universal, energy-efficient, integration-friendly approach to generate z-spin current by electric asymmetry design for dense and low-power spin-torque memory and computing technologies and will stimulate investigation of z-spin currents in various polycrystalline materials.