A comprehensive comparison of molecular and phenotypic profiles between hepatitis B virus (HBV)-infected and non-HBV-infected hepatocellular carcinoma by multi-omics analysis.

Hepatitis B virus (HBV) infection is a major etiology of hepatocellular carcinoma (HCC). An interesting question is how different are the molecular and phenotypic profiles between HBV-infected (HBV+) and non-HBV-infected (HBV-) HCCs? Based on the publicly available multi-omics data for HCC, including bulk and single-cell data, and the data we collected and sequenced, we performed a comprehensive comparison of molecular and phenotypic features between HBV+ and HBV- HCCs. Our analysis showed that compared to HBV- HCCs, HBV+ HCCs had significantly better clinical outcomes, higher degree of genomic instability, higher enrichment of DNA repair and immune-related pathways, lower enrichment of stromal and oncogenic signaling pathways, and better response to immunotherapy. Furthermore, in vitro experiments confirmed that HBV+ HCCs had higher immunity, PD-L1 expression and activation of DNA damage response pathways. This study may provide insights into the profiles of HBV+ and HBV- HCCs, and guide rational therapeutic interventions for HCC patients.

Roles of the transcriptional regulators Fts1, YlNrg1, YlTup1, and YlSsn6 in the repression of the yeast-to-filament transition in the dimorphic yeast Yarrowia lipolytica.

In dimorphic fungi, the yeast-to-filament transition critical for cell survival under nutrient starvation is controlled by both activators and repressors. However, very few filamentation repressors are known. Here we report that, in the dimorphic yeast Yarrowia lipolytica, the conserved transcription factor YlNrg1 plays a minor role whereas Fts1, a newly identified Zn(II)2 Cys6 zinc cluster transcription factor, plays a key role in filamentation repression. FTS1 deletion caused hyperfilamentation whereas Fts1 overexpression drastically reduced filamentation. The expression of FTS1 is downregulated substantially during the yeast-to-filament transition. Transcriptome sequencing revealed that Fts1 represses 401 genes, including the filamentation-activating transcription factor genes MHY1, YlAZF1, and YlWOR4 and key cell wall protein genes. Tup1-Ssn6, a general transcriptional corepressor, is involved in the repression of many cellular functions in fungi. We show that both YlTup1 and YlSsn6 strongly repress filamentation in Y. lipolytica. YlTup1 and YlSsn6 together repress 1383 genes, including a large number of transcription factor and cell wall protein genes, which overlap substantially with Fts1-repressed genes. Fts1 interacts with both YlTup1 and YlSsn6, and LexA-Fts1 fusion represses a lexAop-promoter-lacZ reporter in a Tup1-Ssn6-dependent manner. Our findings suggest that Fts1 functions as a transcriptional repressor, directing the repression of target genes through the Tup1-Ssn6 corepressor.

Crosstalk in extrahepatic and hepatic system in NAFLD/NASH.

Non-alcoholic fatty liver disease (NAFLD) has emerged as the most prevalent chronic liver disease globally. Non-alcoholic steatohepatitis (NASH) represents an extremely progressive form of NAFLD, which, without timely intervention, may progress to cirrhosis or hepatocellular carcinoma. Presently, a definitive comprehension of the pathogenesis of NAFLD/NASH eludes us, and pharmacological interventions targeting NASH specifically remain constrained. The aetiology of NAFLD encompasses a myriad of external factors including environmental influences, dietary habits and gender disparities. More significantly, inter-organ and cellular interactions within the human body play a role in the development or regression of the disease. In this review, we categorize the influences affecting NAFLD both intra- and extrahepatically, elaborating meticulously on the mechanisms governing the onset and progression of NAFLD/NASH. This exploration delves into progress in aetiology and promising therapeutic targets. As a metabolic disorder, the development of NAFLD involves complexities related to nutrient metabolism, liver-gut axis interactions and insulin resistance, among other regulatory functions of extraneous organs. It further encompasses intra-hepatic interactions among hepatic cells, Kupffer cells (KCs) and hepatic stellate cells (HSCs). A comprehensive understanding of the pathogenesis of NAFLD/NASH from a macroscopic standpoint is instrumental in the formulation of future therapies for NASH.

Targeting aberrant glycosylation to modulate microglial response and improve cognition in models of Alzheimer's disease.

Altered glycosylation profiles have been correlated with potential drug targets in various diseases, including Alzheimer's disease (AD). In this area, the linkage between bisecting N-acetylglucosamine (GlcNAc), a product of N-acetylglucosaminyltransferase III (GnT-III), and AD has been recognized, however, our understanding of the cause and the causative role of this aberrant glycosylation in AD are far from completion. Moreover, the effects and mechanisms of glycosylation-targeting interventions on memory and cognition, and novel targeting strategies are worth further study. Here, we showed the characteristic amyloid pathology-induced and age-related changes of GnT-III, and identified transcription factor 7-like 2 as the key transcription factor responsible for the abnormal expression of GnT-III in AD. Upregulation of GnT-III aggravated cognitive dysfunction and Alzheimer-like pathologies. In contrast, loss of GnT-III could improve cognition and alleviate pathologies. Furthermore, we found that an increase in bisecting GlcNAc modified ICAM-1 resulted in impairment of microglial responses, and genetic inactivation of GnT-III protected against AD mechanistically by blocking the aberrant glycosylation of ICAM-1 and subsequently modulating microglial responses, including microglial motility, phagocytosis ability, homeostatic/reactive state and neuroinflammation. Moreover, by target-based screening of GnT-III inhibitors from FDA-approved drug library, we identified two compounds, regorafenib and dihydroergocristine mesylate, showing pharmacological potential leading to modulation of aberrant glycosylation and microglial responses, and rescue of memory and cognition deficits.

von Hippel-Lindau-targeting microRNA-143-3p attenuates mitochondrial abnormality via AMPK/PGC-1α axis in Parkinson's disease.

Parkinson's disease (PD) is the second most common neurodegenerative disease characterized by selective loss of dopaminergic neurons. We previously found that inhibition of von Hippel-Lindau (VHL) can alleviate dopaminergic neuron degeneration in PD models via regulation of mitochondrial homeostasis, however, the disease-related alterations of VHL and the regulatory mechanisms of VHL level in PD need to be further investigated. In this study, we found that the levels of VHL were markedly increased in multiple cell models of PD and identified microRNA-143-3p (miR-143-3p) as a promising candidate for regulating VHL expression involved in PD. miR-143-3p directly bound to the 3'untranslated region of human VHL mRNA and inhibited its translation, and exerted neuroprotective effects by improving cell viability, apoptosis and tyrosine hydroxylase abnormality. Furthermore, we demonstrated that miR-143-3p exerted neuroprotection by attenuating mitochondrial abnormality via AMP-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) axis, and AMPK inhibitor abolished the beneficial effects of miR-143-3p on the cell model of PD. Therefore, we identify the dysregulated VHL and miR-143-3p in PD, and propose the therapeutic potential of miR-143-3p to alleviate PD by improving mitochondrial homeostasis via AMPK/PGC-1α axis.

Self-assembled nanoparticles based on DNA origami and a nitrated T helper cell epitope as a platform for the development of personalized cancer vaccines.

Neoantigen vaccines constitute an emerging and promising cancer immunotherapy. However, not all neoantigens have anti-tumor activity, as poor CD4+ epitope recognition can lead to the lack of greatly limit the persistence of the CD8+ T cell response. Therefore, we designed a self-assembled nanoplatform hereinafter referred to as DNA-coupled nitrated T helper cell epitope nanoparticle (DCNP) based on DNA origami containing a nitrated CD4 + T cell epitope, which can facilitate the effective activation of neoantigen-specific CD8+ T cells. Moreover, we embedded the cytidine-phosphate-guanosine oligonucleotide (CpG ODN) motif sequence in the DNA skeleton to function as a built-in adjuvant to activate Toll-like receptor 9. DCNP can markedly improve adjuvant and neoantigen co-delivery to lymphoid organs and promote neoantigen presentation on dendritic cells. Moreover, DCNP induced robust, and long-lived neoantigen-specific CD8+ T cell responses that significantly delayed tumor growth. Further, these effects were largely dependent on the nitrated T cell epitope. Collectively, our findings indicate that DCNP is a promising platform that could improve the development of personalized therapeutic neoantigen vaccines for cancer immunotherapy.

Inhibiting von Hippel‒Lindau protein-mediated Dishevelled ubiquitination protects against experimental parkinsonism.

Dopaminergic neuron degeneration is a hallmark of Parkinson's disease (PD). We previously reported that the inactivation of von Hippel‒Lindau (VHL) alleviated dopaminergic neuron degeneration in a C. elegans model. In this study, we investigated the specific effects of VHL loss and the underlying mechanisms in mammalian PD models. For in vivo genetic inhibition of VHL, AAV-Vhl-shRNA was injected into mouse lateral ventricles. Thirty days later, the mice received MPTP for 5 days to induce PD. Behavioral experiments were conducted on D1, D3, D7, D14 and D21 after the last injection, and the mice were sacrificed on D22. We showed that knockdown of VHL in mice significantly alleviated PD-like syndromes detected in behavioral and biochemical assays. Inhibiting VHL exerted similar protective effects in MPP+-treated differentiated SH-SY5Y cells and the MPP+-induced C. elegans PD model. We further demonstrated that VHL loss-induced protection against experimental parkinsonism was independent of hypoxia-inducible factor and identified the Dishevelled-2 (DVL-2)/ß-catenin axis as the target of VHL, which was evolutionarily conserved in both C. elegans and mammals. Inhibiting the function of VHL promoted the stability of ß-catenin by reducing the ubiquitination and degradation of DVL-2. Thus, in vivo overexpression of DVL-2, mimicking VHL inactivation, protected against PD. We designed a competing peptide, Tat-DDF-2, to inhibit the interaction between VHL and DVL-2, which exhibited pharmacological potential for protection against PD in vitro and in vivo. We propose the therapeutic potential of targeting the interaction between VHL and DVL-2, which may represent a strategy to alleviate neurodegeneration associated with PD.

Structure and function characterization of the α-L-arabinofuranosidase from the white-rot fungus Trametes hirsuta.

α-L-Arabinofuranosidases (Abfs) play a crucial role in the degradation of hemicelluloses, especially arabinoxylans (AX). Most of the available characterized Abfs are from bacteria, while fungi, as natural decomposers, contain Abfs with little attention given. An arabinofuranosidase (ThAbf1), belonging to the glycoside hydrolase 51 (GH51) family, from the genome of the white-rot fungus Trametes hirsuta, was recombinantly expressed, characterized, and functionally determined. The general biochemical properties showed that the optimal conditions for ThAbf1 were pH 6.0 and 50°C. In substrate kinetics assays, ThAbf1 preferred small fragment arabinoxylo-oligosaccharides (AXOS) and could surprisingly hydrolyze di-substituted 23,33-di-L-arabinofuranosyl-xylotriose (A2,3XX). It also synergized with commercial xylanase (XYL) and increased the saccharification efficiency of arabinoxylan. The crystal structure of ThAbf1 indicated the presence of an adjacent cavity next to the catalytic pocket which led to the ability of ThAbf1 to degrade di-substituted AXOS. The narrow binding pocket prevents ThAbf1 from binding larger substrates. These findings have strengthened our understanding of the catalytic mechanism of GH51 family Abfs and provided a theoretical foundation for the development of more efficient and versatile Abfs to accelerate the degradation and biotransformation of hemicellulose in biomass. KEY POINTS: • ThAbf1 from Trametes hirsuta degraded di-substituted arabinoxylo-oligosaccharide. • ThAbf1 performed detailed biochemical characterization and kinetics. • ThAbf1 structure has been obtained to illustrate the substrate specificity.

Multi-angle excited MOI and image processing strategies specified for detection of orthogonal weld defects.

This paper develops an integrative scheme combining new image acquisition, filtering and enhancement methods specified for orthogonal weld defect detection based on magneto-optical imaging (MOI) technique. For image acquisition, a controllable magnetic system enabling rotation of magnetic angles is invented to accurately collect MO images. Multiple images are acquired, yet few are utilized for further processing in the conventional method based on human subjective preferences, bearing chances that images containing defects are discarded. Therefore, we turn to an automated-filtering system to scrutinize MO images and filter effective images through Bhattacharyya coefficient screening method. This not only elevates efficiency and objectivity but also eliminates missed inspection. For image enhancement, normalization method is used to balance the image intensity, followed by image fusion and edge extraction by a two-dimensional gradient method. Our pre- and post-processing approaches significantly improve accuracy in defect recognition and precision in MO images.

Cytosolic Protein Delivery for Intracellular Antigen Targeting Using Supercharged Polypeptide Delivery Platform.

Despite the well-recognized clinical success of therapeutic proteins, especially antibodies, their inability to penetrate the cell membrane restricts them to secretory extracellular or membrane-associated targets. Developing a direct cytosolic protein delivery system would offer unique opportunities for intracellular target-related therapeutic proteins. Here, we generated a supercharged polypeptide (SCP) with high cellular uptake efficiency, endosomal escape ability, and good biosafety and developed an SCP with an unnatural amino acid containing the phenylboronic acid (PBA) group, called PBA-SCP. PBA-SCP is capable of potently delivering proteins with various isoelectric points and molecular sizes into the cytosol of living cells without affecting their bioactivities. Importantly, cytosolically delivered antibodies remain functional and are capable of targeting, labeling, and manipulating diverse intracellular antigens. This study demonstrates an efficient and versatile intracellular protein delivery platform, especially for antibodies, and provides new possibilities for expanding protein-based therapeutics to intracellular "undruggable" targets.

Polysaccharides catabolism by the human gut bacterium -Bacteroides thetaiotaomicron: advances and perspectives.

In recent years, the degradation processes of polysaccharides by human gut microbiota are receiving considerable attention due to the discoveries of the powerful function of gut microbiota. Gut microbiota has developed a sensitive, accurate, and complex system for sensing, capturing, and degrading different polysaccharides. Among the gut microbiota, Bacteroides thetaiotaomicron, a representative species of Bacteroides, is considered as the best degrader of polysaccharides and a potential probiotic in pharmaceutical and food industries. Here, we summarize the degradation system of B. thetaiotaomicron and the degradation pathways of different polysaccharides by B. thetaiotaomicron. We also describe a technical route for investigating a specific polysaccharide degradation pathway by human gut bacteria. In addition, we also provide the future perspectives in the development of novel polysaccharides or oligosaccharides drugs, precision microbiology medicine, and personalized nutrition.

The relationship between internal migration and the likelihood of high-risk pregnancy: Hukou system and high-risk pregnancies in China.

BACKGROUND: China has one of the world's largest internal migrant populations. The Chinese Hukou system is a unique household registration system that limits internal migrants in their access to basic urban public services, such as public health insurance and social assistance of their host city. In the case of female internal migrants, this may lead to high-risk pregnancies. The objective of this study is to assess the relationship between internal migrant status (Hukou) and the likelihood of high-risk pregnancies that occur in one large municipal-level obstetrics hospital in Shanghai, China. METHODS: Medical records data from the Shanghai First Maternity and Infant Hospital from January 1, 2013, to May 31, 2018, were used to analyze 133,358 live births for Shanghai natives (n = 83,872) and internal migrant women (n = 49,486). A propensity score matching approach was used in conjunction with logistic regression analysis to identify the role of internal migrant status (Hukou) on the likelihood of high-risk pregnancies. RESULTS: A greater likelihood of high-risk pregnancies were found among internal migrant women who moved from other parts of China to Shanghai. This effect was more obvious for women who gave birth for the first time and internal migrant women who were employed. CONCLUSION: The results show the effects of internal migrant status (Hukou) and the elevated likelihood of high-risk pregnancies among internal migrant women relative to their urban counterparts in Shanghai even after accounting for self-selection by employing the propensity score matching method. China's unique Hukou household registration system limits access to public services for internal migrant women and accordingly may account for the elevated likelihood of high-risk pregnancies.

Characterization of the promoter, downstream target genes and recognition DNA sequence of Mhy1, a key filamentation-promoting transcription factor in the dimorphic yeast Yarrowia lipolytica.

Msn2/Msn4-family zinc finger transcription factors play important roles in stress response in yeast. However, some members of this family show significant functional divergence in different species. Here, we report that in the dimorphic yeast Yarrowia lipolytica, the Msn2/Msn4-like protein Mhy1 is a key regulator of yeast-to-hypha dimorphic transition but not stress response. Both MHY1 deletion and overexpression affect filamentation. In contrast, YlMsn4, the other Msn2/Msn4-like protein, regulates tolerance to acid-induced stress. We show that MHY1 has an unusually long (about 3800 bp) promoter featuring an upstream located enhancer and a double stress response element (STRE) motif, the latter of which mediates Mhy1's regulation on its own transcription. Transcriptome profiling conducted in wild-type strain, mhy1Δ mutant and MHY1-overexpressing mutant revealed about 100 genes that are highly differentially expressed (≥ 5-fold) in each of the 2 mutants compared to the wild-type strain. The largest group of genes downregulated in mhy1Δ mutant encodes cell wall proteins or enzymes involved in cell wall organization, suggesting that Mhy1 may regulate dimorphic transition by controlling these cell wall genes. We confirmed that the genes YALI0C23452, YALI0C15268 and YALI0B09955 are directly regulated by Mhy1. We also characterized the Mhy1 consensus binding site as 5'-WNAGGGG-3' (W = A or T; N = A, T, G or C). These results provide new insight in the functions of Msn2/Msn4-family transcription factors in fungi and the mechanism by which Mhy1 regulates dimorphic transition.

Roles of the PH, coiled-coil and SAM domains of the yeast polarity protein Boi2 in polarity-site localization and function in polarized growth.

Boi1 and Boi2 are paralogous proteins essential for bud formation in budding yeast. So far, the domains that target Boi1/Boi2 to the polarity sites and function in bud formation are not well understood. Here, we report that a coiled-coil domain of Boi2 cooperates with the adjacent PH domain to confer Boi2's bud-cortex localization and major function in cell growth. The PH domain portion of the PH-CC bi-domain interacts with the Rho GTPases Cdc42 and Rho3 and both interactions are independent of the GTP/GDP-bound state of each GTPase. Interestingly, high-copy RHO3 and BOI2 but not CDC42 suppressed the growth defect of RGA1-C538 overexpression and the sec15-1 mutant and this BOI2 function depends on RHO3, suggesting that Boi2 may function in the Rho3 pathway. The SAM domain of Boi2 plays an essential role in high-copy suppression of the two mutants as well as in the early bud-neck localization of Boi2. The SAM domain and the CC domain also interact homotypically. They are likely involved in the formation of Boi2-containing protein complex. Our results provide new insights in the localization and function of Boi2 and highlight the importance of the PH-CC bi-domain and the SAM domain in Boi2's localization and function.

The Sur7/PalI family transmembrane protein Tos7 (Yol019w) plays a role in secretion in budding yeast.

Tos7 (Yol019w) is a Sur7/PalI family transmembrane protein in the budding yeast Saccharomyces cerevisiae. Since the deletion of TOS7 did not affect growth or cell morphology, the cellular roles of Tos7 have not been established previously. Here, we show that high-copy TOS7 expression suppressed the growth defect of the secretion-defective RGA1-C term-overexpressing mutant and sec15-1 mutant. Moreover, Tos7 physically interacted with Boi2 and the Rho GTPase Rho3, two key regulators of exocyst assembly, suggesting that Tos7 plays a role in secretion. We also show that the deletion of TOS7 rendered the cells more sensitive to the cell wall-disrupting agents Congo red and calcofluor white while high-copy TOS7 expression had an opposite effect, suggesting that Tos7 affects cell wall organization. Finally, we show that Tos7 localized to punctate patches on the plasma membrane that were largely co-localized with the plasma membrane microdomains named MCC (membrane compartment of Can1). Together, these results suggest that Tos7 contributes to cell surface-related functions. Tos7 is likely an auxiliary component of MCC/eisosome that specifically interacts with the secretory pathway.

Monitoring of keyhole entrance and molten pool with quality analysis during adjustable ring mode laser welding.

The process monitoring of the top side and the evaluation of surface quality were applied in adjustable ring mode (ARM) laser welding of 316 stainless steel by using visual monitoring and confocal sensor technology. Experiments were conducted in different power arrangements of an ARM laser. In this study, the process status was evaluated based on the area of keyhole entrance and the width of the pool. The geometric characteristics of the topside weld were measured by a confocal sensor. The shape of the fusion zone was analyzed based on its cross section. The process mechanism of a different mode of ARM laser welding was investigated by analyzing the process status and geometric characteristics of the surface bead. Experimental results showed that dual-mode laser welding could stabilize the keyhole entrance with a uniform weld surface formation in comparison to the pure ring-mode laser weld. The dual-mode laser also generated a wider molten pool with a wider fusion zone than the pure center laser weld.

Microenvironment-Responsive Delivery of the Cas9 RNA-Guided Endonuclease for Efficient Genome Editing.

Successful and efficient delivery of Cas9 protein and gRNA into cells is critical for genome editing and its therapeutic application. In this study, we developed an improved supercharged polypeptide (SCP) mediated delivery system based on dithiocyclopeptide linker to realize the effective genome editing in tumor cells. The fusion protein Cas9-linker-SCP (Cas9-LS) forms positively charged complexes with gRNA in vitro to provide possibilities for gRNA delivery into cells. Under the microenvironment of tumor cells, the dithiocyclopeptide linker, containing matrix metalloproteinase 2 (MMP-2) sensitive sequence and an intramolecular disulfide bond, can be completely disconnected to promote the release of Cas9 protein with the nuclear localization sequence (NLS) in the cytoplasm and transfer to the cell nucleus for highly efficient genome editing, resulting in an obvious increase of indel efficiency in comparison to fusion protein without dithiocyclopeptide linker (Cas9-SCP). Furthermore, Cas9-LS shows no significant cytotoxicity and minimal hemolytic activity. We envision that the microenvironment-responsive Cas9 protein delivery system can facilitate more efficient genome editing in tumor cells.

Establishment of an HPLC-based method to identify key proteases of proteins in vitro.

Given that the biological functions of proteins may decrease or even be lost due to degradation by proteases, it is of great significance to identify potential proteases that degrade protein drugs during systemic circulation. In this work, we describe a method based on high-performance liquid chromatography (HPLC) to identify key proteases that degrade therapeutic proteins in blood, including endopeptidases and exopeptidases. Here, the degradation of proteins was detected by competition with standard substrates of proteases and is shown as the relative residue rate. Four protein drugs were subjected to this method, and the results suggested that growth hormone was degraded by aminopeptidase N and kallikrein-related peptidase 5, pertuzumab was hardly degraded by the proteases, factor VII was degraded by carboxypeptidase B, neprilysin, dipeptidyl peptidase-4 and peptidyl dipeptidase A, and fibrinogen was degraded by carboxypeptidase B and kallikrein-related peptidase 5, findings consistent with the literature. The results were confirmed by microscale thermophoresis; additionally, activity detection in vitro substantiated that the degradation of factor VII decreased its activity. We demonstrate that this method can be used to identify key proteases of proteins with high accuracy, precision and durability.

Magneto-optical imaging feature extraction of micro-gap weld joint under nonuniform magnetic field excitation.

To reduce the effect of the nonuniformity of magnetic field excitation on micro-gap weld joint magneto-optical (MO) imaging, a new experimental system based on the Faraday MO effect to detect micro-gap welds (gap width less than 0.1 mm) under nonuniform magnetic field excitation was developed. Horseshoe permanent magnets were used to magnetize the weldment and establish a nonuniform magnetic field at the welding joint. MO images of the micro-gap weld joint were captured using an MO sensor under nonuniform magnetic field excitation. After analyzing the distribution characteristics of the magnetic induction intensity in the weld joint area, a characterization method for the weld zone slope was proposed. The weld zone slope could accurately determine the MO imaging effects under the nonuniform magnetic field. A model based on an error backpropagation (BP) neural network was used to predict the offset of the weld joint center at each moment, and the results performed by BP were utilized to optimize the measured value of the weld joint center. Experimental results show that it can accurately extract the position of micro-gap welds under nonuniform magnetic field excitation.

The effects of compulsory health insurance on birth outcomes: evidence from China's UEBMI scheme.

BACKGROUND: Despite extensive research concerning the impact of health insurance on the advancement of infant health in developed countries, few studies have adjusted their results for potential confounding due to adverse selection in insurance coverage, wherein those who anticipate a need for health services tend to be the ones that acquire insurance. The presence of compulsory health insurance in China, such as the Urban Employee Basic Medical Insurance (UEBMI) scheme may provide an opportunity to estimate the effect of health insurance on infant health, by reducing the endogeneity problem into insurance due to the adverse selection. The objective is to assess the relationship between UEBMI and infant health outcomes in one sizeable municipal-level obstetrics hospital in Shanghai, East China. METHODS: Medical records data from the Shanghai First Maternity and Infant Hospital from January 1, 2013 to April 30, 2019 were used to form an analysis dataset of 160,429 live births which was comprised of Shanghai residents with UEBMI coverage (n = 101,153) and women without any insurance coverage (n = 59,276). A propensity score matching approach using conjoint quantile regression and probit regression models was used to eliminate latent endogeneity of UEBMI coverage in order to garner robust results. Further analysis stratified by maternal migrant status was conducted to further assess the sensitivity of the findings to distinct patient subgroups. RESULTS: The UEBMI scheme was shown to be associated with improvements in infant birth outcomes. The scheme was associated with: an increase in birth weight of about 30 g (p <  0.001, 95% CI 23.908-35.295). This finding was evident in other five different birth outcomes (premature birth, low birth weight, very low birth weight, low Apgar score, and an abnormal health condition at birth). After stratifying by migrant status, the UEBMI was shown to have a greater effect on migrants compared to local residents of Shanghai. CONCLUSIONS: Our findings suggest that health insurance coverage for pregnant women, especially for migrants, has the potential to significantly and directly improve infant health outcomes. Further research is required to determine whether these findings can be replicated for other Chinese jurisdictions.