Identifying Medical Diagnoses and Treatable Diseases by Image-Based Deep Learning.

The implementation of clinical-decision support algorithms for medical imaging faces challenges with reliability and interpretability. Here, we establish a diagnostic tool based on a deep-learning framework for the screening of patients with common treatable blinding retinal diseases. Our framework utilizes transfer learning, which trains a neural network with a fraction of the data of conventional approaches. Applying this approach to a dataset of optical coherence tomography images, we demonstrate performance comparable to that of human experts in classifying age-related macular degeneration and diabetic macular edema. We also provide a more transparent and interpretable diagnosis by highlighting the regions recognized by the neural network. We further demonstrate the general applicability of our AI system for diagnosis of pediatric pneumonia using chest X-ray images. This tool may ultimately aid in expediting the diagnosis and referral of these treatable conditions, thereby facilitating earlier treatment, resulting in improved clinical outcomes. VIDEO ABSTRACT.

Single electrons on solid neon as a solid-state qubit platform.

Progress towards the realization of quantum computers requires persistent advances in their constituent building blocks-qubits. Novel qubit platforms that simultaneously embody long coherence, fast operation and large scalability offer compelling advantages in the construction of quantum computers and many other quantum information systems1-3. Electrons, ubiquitous elementary particles of non-zero charge, spin and mass, have commonly been perceived as paradigmatic local quantum information carriers. Despite superior controllability and configurability, their practical performance as qubits through either motional or spin states depends critically on their material environment3-5. Here we report our experimental realization of a qubit platform based on isolated single electrons trapped on an ultraclean solid neon surface in vacuum6-13. By integrating an electron trap in a circuit quantum electrodynamics architecture14-20, we achieve strong coupling between the motional states of a single electron and a single microwave photon in an on-chip superconducting resonator. Qubit gate operations and dispersive readout are implemented to measure the energy relaxation time T1 of 15 µs and phase coherence time T2 over 200 ns. These results indicate that the electron-on-solid-neon qubit already performs near the state of the art for a charge qubit21.

SLC25A3 negatively regulates NLRP3 inflammasome activation by restricting the function of NLRP3.

The NACHT, leucine-rich repeat, and pyrin domains-containing protein 3 (collectively known as NLRP3) inflammasome activation plays a critical role in innate immune and pathogenic microorganism infections. However, excessive activation of NLRP3 inflammasome will lead to cellular inflammation and tissue damage, and naturally it must be precisely controlled in the host. Here, we discovered that solute carrier family 25 member 3 (SLC25A3), a mitochondrial phosphate carrier protein, plays an important role in negatively regulating NLRP3 inflammasome activation. We found that SLC25A3 could interact with NLRP3, overexpression of SLC25A3 and knockdown of SLC25A3 could regulate NLRP3 inflammasome activation, and the interaction of NLRP3 and SLC25A3 is significantly boosted in the mitochondria when the NLRP3 inflammasome is activated. Our detailed investigation demonstrated that the interaction between NLRP3 and SLC25A3 disrupted the interaction of NLRP3-NEK7, promoted ubiquitination of NLRP3, and negatively regulated NLRP3 inflammasome activation. Thus, these findings uncovered a new regulatory mechanism of NLRP3 inflammasome activation, which provides a new perspective for the therapy of NLRP3 inflammasome-associated inflammatory diseases.

Physical Contacts Between Mitochondria and WPBs Participate in WPB Maturation.

BACKGROUND: Weibel-Palade bodies (WPBs) are endothelial cell-specific cigar-shaped secretory organelles containing various biologically active molecules. WPBs play crucial roles in thrombosis, hemostasis, angiogenesis, and inflammation. The main content of WPBs is the procoagulant protein vWF (von Willebrand factor). Physical contacts and functional cross talk between mitochondria and other organelles have been demonstrated. Whether an interorganellar connection exists between mitochondria and WPBs is unknown. METHODS: We observed physical contacts between mitochondria and WPBs in human umbilical vein endothelial cells by electron microscopy and living cell confocal microscopy. We developed an artificial intelligence-assisted method to quantify the duration and length of organelle contact sites in live cells. RESULTS: We found there existed physical contacts between mitochondria and WPBs. Disruption of mitochondrial function affected the morphology of WPBs. Furthermore, we found that Rab3b, a small GTPase on the WPBs, was enriched at the mitochondrion-WPB contact sites. Rab3b deficiency reduced interaction between the two organelles and impaired the maturation of WPBs and vWF multimer secretion. CONCLUSIONS: Our results reveal that Rab3b plays a crucial role in mediating the mitochondrion-WPB contacts, and that mitochondrion-WPB coupling is critical for the maturation of WPBs in vascular endothelial cells.

Nrf2 prevents diabetic cardiomyopathy via antioxidant effect and normalization of glucose and lipid metabolism in the heart.

Metabolic disorders and oxidative stress are the main causes of diabetic cardiomyopathy. Activation of nuclear factor erythroid 2-related factor 2 (Nrf2) exerts a powerful antioxidant effect and prevents the progression of diabetic cardiomyopathy. However, the mechanism of its cardiac protection and direct action on cardiomyocytes are not well understood. Here, we investigated in a cardiomyocyte-restricted Nrf2 transgenic mice (Nrf2-TG) the direct effect of Nrf2 on cardiomyocytes in DCM and its mechanism. In this study, cardiomyocyte-restricted Nrf2 transgenic mice (Nrf2-TG) were used to directly observe whether cardiomyocyte-specific overexpression of Nrf2 can prevent diabetic cardiomyopathy and correct glucose and lipid metabolism disorders in the heart. Compared to wild-type mice, Nrf2-TG mice showed resistance to diabetic cardiomyopathy in a streptozotocin-induced type 1 diabetes mouse model. This was primarily manifested as improved echocardiography results as well as reduced myocardial fibrosis, cardiac inflammation, and oxidative stress. These results showed that Nrf2 can directly act on cardiomyocytes to exert a cardioprotective role. Mechanistically, the cardioprotective effects of Nrf2 depend on its antioxidation activity, partially through improving glucose and lipid metabolism by directly targeting lipid metabolic pathway of AMPK/Sirt1/PGC-1α activation via upstream genes of sestrin2 and LKB1, and indirectly enabling AKT/GSK-3ß/HK-Ⅱ activity via AMPK mediated p70S6K inhibition.

Nitrogen Effects Endowed by Doping Electron-Withdrawing Nitrogen Atoms into Polycyclic Aromatic Hydrocarbon Fluorescence Emitters.

Unveiling innovative mechanisms to design new highly efficient fluorescent materials and, thereby, fabricate high-performance organic light-emitting diodes (OLEDs) is a concerted endeavor in both academic and industrial circles. Polycyclic aromatic hydrocarbons (PAHs) have been widely used as fluorescent emitters in blue OLEDs, but device performances are far from satisfactory. In response, we propose the concept of "nitrogen effects" endowed by doping electron-withdrawing nitrogen atoms into PAH fluorescence emitters. The presence of the n orbital on the imine nitrogen is conducive to promoting electron coupling, which leads to increased molar absorptivity and an accelerated radiative decay rate of emitters, thereby facilitating the Förster energy transfer (FET) process in the OLEDs. Additionally, electronically withdrawing nitrogen atoms enhances host-guest interactions, thereby positively affecting the FET process and the horizontal orientation factor of the emitting layer. To validate the "nitrogen effects" concept, cobalt-catalyzed multiple C-H annulation has been utilized to incorporate alkynes into the imine-based frameworks, which enables various imine-embedded PAH (IE-PAH) fluorescence emitters. The cyclization demonstrates notable regioselectivity, thereby offering a practical tool to precisely introduce peripheral groups at desired positions with bulky alkyl units positioned adjacent to the nitrogen atoms, which were previously beyond reach through the Friedel-Crafts reaction. Blue OLEDs fabricated with IE-PAHs exhibit outstanding performance with a maximum external quantum efficiency (EQEmax) of 32.7%. This achievement sets a groundbreaking record for conventional blue PAH-based fluorescent emitters, which have an EQEmax of 24.0%.

Modulating the Primary and Secondary Coordination Spheres of Single Ni(II) Sites in Metal-Organic Frameworks for Boosting Photocatalysis.

Though the coordination environment of single metal sites has been recognized to be of great importance in promoting catalysis, the influence of simultaneous precise modulation of primary and secondary coordination spheres on catalysis remains largely unknown. Herein, a series of single Ni(II) sites with altered primary and secondary coordination spheres have been installed onto metal-organic frameworks (MOFs) with UiO-67 skeleton, affording UiO-Ni-X-Y (X = S, O; Y = H, Cl, CF3) with X and Y on the primary and secondary coordination spheres, respectively. Upon deposition with CdS nanoparticles, the resulting composites present high photocatalytic H2 production rates, in which the optimized CdS/UiO-Ni-S-CF3 exhibits an excellent activity of 13.44 mmol g-1, ∼500 folds of the pristine catalyst (29.6 µmol g-1 for CdS/UiO), in 8 h, highlighting the key role of microenvironment modulation around Ni sites. Charge kinetic analysis and theoretical calculation results demonstrate that the charge transfer dynamics and reaction energy barrier are closely correlated with their coordination spheres. This work manifests the advantages of MOFs in the fabrication of structurally precise catalysts and the elucidation of particular influences of microenvironment modulation around single metal sites on the catalytic performance.

Unlocking Structurally Nontraditional Naphthyridine-Based Electron-Transporting Materials with C-H Activation-Annulation.

The inherent benefits of C-H activation have given rise to innovative approaches in designing organic optoelectronic molecules that depart from conventional methods. While theoretical calculations have suggested the suitability of the 2,6-naphthyridine scaffold for electron transport materials (ETMs) in organic light-emitting diodes (OLEDs), the existing synthetic methodologies have proven to be insufficient for the construction of multiple arylated and fully aryl-substituted molecules. Herein, we present a solution for the synthesis of 2,6-naphthyridine derivatives, with the rhodium-catalyzed consecutive C-H activation-annulation process of fumaric acid with alkynes standing as the pivotal step within this strategy. The ETMs, purposefully designed and synthesized based on the 2,6-naphthyridine framework, exhibit an impressively high glass-transition temperature (Tg) of 282 °C and high electron mobility (µe), setting a new benchmark for ETMs in OLEDs with a µe exceeding 10-2 cm2 V-1 s-1. These materials prove to be versatile ETM candidates suitable for red, green, and blue phosphorescent OLED devices.

Regioselective N-Trideuteromethylation of Tautomeric Polyaza Heterocycles.

Methods for regioselective N-trideuteromethylation of tautomeric polyaza heterocycles are highly sought-after. Disclosed herein is an N-trideuterated methylation reaction of imidazoles and pyrazoles with high regioselectivity and deuterium purity using easily available CF3SO3CD3 as the -CD3 source. This method enables the easy synthesis of important deuterium-labeled azoles, including dimetridazole-d3, ipronidazole-d3, hydroxy dimetridazole-d3, and ronidazole-d3.

An evaluation of dexmedetomidine in combination with midazolam in pediatric sedation: a systematic review and meta-analysis.

BACKGROUND: Dexmedetomidine and midazolam are commonly used sedatives in children. We conducted a systematic review and meta-analysis to compare the safety and effectiveness of sedation provided by dexmedetomidine combined with midazolam versus other sedatives including chloral hydrate, midazolam and other sedatives in pediatric sedation. METHODS: The Embase, Web of Science, Cochrane Library, and PubMed databases, and Clinicaltrials.gov register of controlled trials were searched from inception to June 2022. All randomized controlled trials used dexmedetomidine-midazolam in pediatric sedation were enrolled. The articles search, data extraction, and quality assessment of included studies were performed independently by two researchers. The success rate of sedation was considered as the primary outcome. The secondary outcomes included onset time of sedation, recovery time of sedation and occurrence of adverse events. RESULTS: A total of 522 studies were screened and 6 RCTs were identified; 859 patients were analyzed. The administration of dexmedetomidine combined with midazolam was associated with a higher sedation success rate and a lower incidence of nausea and vomiting in computed tomography, magnetic resonance imaging, Auditory Brainstem Response test or fiberoptic bronchoscopy examinations than the other sedatives did (OR = 2.92; 95% CI: 1.39-6.13, P = 0.005, I2 = 51%; OR = 0.23, 95% CI: 0.07-0.68, P = 0.008, I2 = 0%, respectively). Two groups did not differ significantly in recovery time and the occurrence of adverse reactions (WMD = - 0.27, 95% CI: - 0.93 to - 0.39, P = 0.42; OR 0.70; 95% CI: 0.48-1.02, P = 0.06, I2 = 45%. respectively). However, the results of the subgroup analysis of ASA I-II children showed a quicker onset time in dexmedetomidine-midazolam group than the other sedatives (WMD=-3.08; 95% CI: -4.66 to - 1.49, P = 0.0001, I2 = 30%). CONCLUSIONS: This meta-analysis showed that compared with the control group, dexmedetomidine combined with midazolam group provided higher sedation success rates and caused a lower incidence of nausea and vomiting in completing examinations, indicating a prospective outpatient clinical application for procedural sedation.

A Non-Disposable Electrochemical Sensor Based on Laser-Synthesized Pd/LIG Nanocomposite-Modified Screen-Printed Electrodes for the Detection of H2O2.

There have been many studies on the significant correlation between the hydrogen peroxide content of different tissues or cells in the human body and the risk of disease, so the preparation of biosensors for detecting hydrogen peroxide concentration has been a hot topic for researchers. In this paper, palladium nanoparticles (PdNPs) and laser-induced graphene (LIG) were prepared by liquid-phase pulsed laser ablation and laser-induced technology, respectively. The complexes were prepared by stirring and used for the modification of screen-printed electrodes to develop a non-enzymatic hydrogen peroxide biosensor that is low cost and mass preparable. The PdNPs prepared with anhydrous ethanol as a solvent have a uniform particle size distribution. The LIG prepared by laser direct writing has good electrical conductivity, and its loose porous structure provides more adsorption sites. The electrochemical properties of the modified electrode were characterized by cyclic voltammetry, chronoamperometry, and electrochemical impedance spectroscopy. Compared with bare screen-printed electrodes, the modified electrodes are more sensitive for the detection of hydrogen peroxide. The sensor has a linear response range of 5 µM-0.9 mM and 0.9 mM-5 mM. The limit of detection is 0.37 µM. The above conclusions indicate that the hydrogen peroxide electrochemical biosensor prepared in this paper has great advantages and potential in electrochemical catalysis.

Electronic Nose Drift Suppression Based on Smooth Conditional Domain Adversarial Networks.

Anti-drift is a new and serious challenge in the field related to gas sensors. Gas sensor drift causes the probability distribution of the measured data to be inconsistent with the probability distribution of the calibrated data, which leads to the failure of the original classification algorithm. In order to make the probability distributions of the drifted data and the regular data consistent, we introduce the Conditional Adversarial Domain Adaptation Network (CDAN)+ Sharpness Aware Minimization (SAM) optimizer-a state-of-the-art deep transfer learning method.The core approach involves the construction of feature extractors and domain discriminators designed to extract shared features from both drift and clean data. These extracted features are subsequently input into a classifier, thereby amplifying the overall model's generalization capabilities. The method boasts three key advantages: (1) Implementation of semi-supervised learning, thereby negating the necessity for labels on drift data. (2) Unlike conventional deep transfer learning methods such as the Domain-adversarial Neural Network (DANN) and Wasserstein Domain-adversarial Neural Network (WDANN), it accommodates inter-class correlations. (3) It exhibits enhanced ease of training and convergence compared to traditional deep transfer learning networks. Through rigorous experimentation on two publicly available datasets, we substantiate the efficiency and effectiveness of our proposed anti-drift methodology when juxtaposed with state-of-the-art techniques.

The Development of Aptamer-Based Gold Nanoparticle Lateral Flow Test Strips for the Detection of SARS-CoV-2 S Proteins on the Surface of Cold-Chain Food Packaging.

The COVID-19 pandemic over recent years has shown a great need for the rapid, low-cost, and on-site detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this study, an aptamer-based colloidal gold nanoparticle lateral flow test strip was well developed to realize the visual detection of wild-type SARS-CoV-2 spike proteins (SPs) and multiple variants. Under the optimal reaction conditions, a low detection limit of SARS-CoV-2 S proteins of 0.68 nM was acquired, and the actual detection recovery was 83.3% to 108.8% for real-world samples. This suggests a potential tool for the prompt detection of SARS-CoV-2 with good sensitivity and accuracy, and a new method for the development of alternative antibody test strips for the detection of other viral targets.

Ultrasmall Coinage Metal Nanoclusters as Promising Theranostic Probes for Biomedical Applications.

Ultrasmall coinage metal nanoclusters (NCs, <3 nm) have emerged as a novel class of theranostic probes due to their atomically precise size and engineered physicochemical properties. The rapid advances in the design and applications of metal NC-based theranostic probes are made possible by the atomic-level engineering of metal NCs. This Perspective article examines (i) how the functions of metal NCs are engineered for theranostic applications, (ii) how a metal NC-based theranostic probe is designed and how its physicochemical properties affect the theranostic performance, and (iii) how metal NCs are used to diagnose and treat various diseases. We first summarize the tailored properties of metal NCs for theranostic applications in terms of biocompatibility and tumor targeting. We focus our discussion on the theranostic applications of metal NCs in bioimaging-directed disease diagnosis, photoinduced disease therapy, nanomedicine, drug delivery, and optical urinalysis. Lastly, an outlook on the challenges and opportunities in the future development of metal NCs for theranostic applications is provided.

The roles of critical pro-inflammatory cytokines in the drive of cytokine storm during SARS-CoV-2 infection.

In patients with severe COVID-19, acute respiratory distress syndrome (ARDS), multiple organ dysfunction syndrome (MODS), and even mortality can result from cytokine storm, which is a hyperinflammatory medical condition caused by the excessive and uncontrolled release of pro-inflammatory cytokines. High levels of numerous crucial pro-inflammatory cytokines, such as interleukin-1 (IL-1), IL-2, IL-6, tumor necrosis factor-α, interferon (IFN)-γ, IFN-induced protein 10 kDa, granulocyte-macrophage colony-stimulating factor, monocyte chemoattractant protein-1, and IL-10 and so on, have been found in severe COVID-19. They participate in cascade amplification pathways of pro-inflammatory responses through complex inflammatory networks. Here, we review the involvements of these critical inflammatory cytokines in SARS-CoV-2 infection and discuss their potential roles in triggering or regulating cytokine storm, which can help to understand the pathogenesis of severe COVID-19. So far, there is rarely effective therapeutic strategy for patients with cytokine storm besides using glucocorticoids, which is proved to result in fatal side effects. Clarifying the roles of key involved cytokines in the complex inflammatory network of cytokine storm will help to develop an ideal therapeutic intervention, such as neutralizing antibody of certain cytokine or inhibitor of some inflammatory signal pathways.

Inhibitors of Keap1-Nrf2 protein-protein interaction reduce estrogen responsive gene expression and oxidative stress in estrogen receptor-positive breast cancer.

Estrogen contributes to the development of breast cancer through estrogen receptor (ER) signaling and by generating genotoxic metabolites that cause oxidative DNA damage. To protect against oxidative stress, cells activate nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream cytoprotective genes that initiate antioxidant responses and detoxify xenobiotics. Nrf2 activation occurs by inhibiting the protein-protein interaction (PPI) between Nrf2 and its inhibitor Keap1, which otherwise targets Nrf2 for ubiquitination and destruction. In this study, we examined a series of novel direct inhibitors of Keap1-Nrf2 PPI in their role in promoting the availability of Nrf2 for antioxidant activity and attenuating estrogen-mediated responses in breast cancer. ER-positive human breast cancer cells MCF-7 were treated with 17ß-estradiol (E2) in the presence or absence of selected Keap1-Nrf2 PPI inhibitors. Keap1-Nrf2 PPI inhibitors suppressed the mRNA and protein levels of estrogen responsive genes induced by E2 exposure, such as PGR. Keap1-Nrf2 PPI inhibitors caused significant activation of Nrf2 target genes. E2 decreased the mRNA and protein level of the Nrf2 target gene NQO1, and the Keap1-Nrf2 PPI inhibitors reversed this effect. The reversal of E2 action by these compounds was not due to binding to ER as ER antagonists. Further, a selected compound attenuated oxidative stress induced by E2, determined by the level of a biomarker 8-oxo-deoxyguanosine. These findings suggest that the Keap1-Nrf2 PPI inhibitors have potent antioxidant activity by activating Nrf2 pathways and inhibit E2-induced gene and protein expression. These compounds may serve as potential chemopreventive agents in estrogen-stimulated breast cancer.

A Cre knockin mouse reveals specific expression of Agouti gene in mesenchymal lineage cells in multiple organs and provides a unique tool for conditional gene targeting.

The mouse Agouti gene encodes a paracrine signaling factor which promotes melanocytes to produce yellow instead of black pigment. It has been reported that Agouti mRNA is confined to the dermal papilla after birth in various mammalian species. In this study, we created and characterized a knockin mouse strain in which Cre recombinase was expressed in-frame with endogenous Agouti coding sequence. The Agouti-Cre mice were bred with reporter mice (Rosa26-tdTomato or Rosa26-ZsGreen) to trace the lineage of Agouti-expressing cells during development. In skin, the reporter was detected in some dermal fibroblasts at the embryonic stage and in all dermal fibroblasts postnatally. It was also expressed in all mesenchymal lineage cells in other organs/tissues, including eyes, tongue, muscle, intestine, adipose, prostate and testis. Interestingly, the reporter expression was excluded from epithelial cells in the above organs/tissues. In brain, the reporter was observed in the outermost meningeal fibroblasts. Our work helps to illustrate the Agouti expression pattern during development and provides a valuable mouse strain for conditional gene targeting in mesenchymal lineage cells in multiple organs.

Anti-inflammatory effects of extracellular vesicles from Morchella on LPS-stimulated RAW264.7 cells via the ROS-mediated p38 MAPK signaling pathway.

Morchella is a kind of important edible and medicinal fungi, which is rich in polysaccharides, enzymes, fatty acids, amino acids and other active components. Extracellular vesicles (EVs) have a typical membrane structure, and the vesicles contain some specific lipids, miRNAs and proteins, and their can deliver the contents to different cells to change their functions. The present study investigated whether Morchella produce extracellular vesicles and its anti-inflammatory effect on lipopolysaccharide (LPS)-induced RAW246.7 macrophages. The experimental results showed that Morchella produced extracellular vesicles and significantly reduced the production of nitric oxide (NO) and reactive oxygen species (ROS) in a model of LPS-induced inflammation. In addition, the expression of inflammatory factor-related genes such as inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2) showed dose-dependent inhibition. Morchella extracellular vesicles also can inhibit the inflammatory response induced by LPS by inhibiting the production of ROS and reducing the phosphorylation levels of the p38 MAPK signaling pathway. These results indicate that the Morchella extracellular vesicles can be used as a potential anti-inflammatory substance in the treatment of inflammatory diseases.

A method for extraction of exosomes from breast tumour cells and characterisation by transmission electron microscopy.

Exosomes can not only be used as markers of tumour metastasis but also be used for noninvasive diagnosis of clinical diseases, which holds significant medical research value. Observing the morphology and distribution of exosomes using transmission electron microscopy (TEM) is highly significant. In this study, we use breast tumour cell (MDA-MB-231) exosomes as a representative sample and focus on the extraction and purification of exosomes, as well as the investigation of optimal conditions for the observation of exosomes using TEM. Through comparative tests, we obtained the optimal dilution concentration and staining method for TEM of exosomes, the best dilution concentration is 100 times, the best negative staining time is 1.5 min. Western blotting and scanning electron microscopy (SEM) confirmed the presence of exosome. The particle size experiment shows that the size of exosomes is mainly distributed between 60 nm and 150 nm. This method provides a reference for TEM sample preparation of subcellular structures and small molecular biomaterials other than exosomes.

A pilot study of Kangaroo mother care in early essential newborn care in resource-limited areas of China: the facilitators and barriers to implementation.

BACKGROUND: Implementation of Kangaroo Mother Care (KMC) in resource-limited areas of China may face unique barriers, such as a lack of resources, geographic location and more traditional culture among others. This qualitative study analyses the facilitators and barriers to implementing KMC in county-level health facilities in resource-limited areas of China for the promotion of KMC on a larger scale. METHODS: Participants from 4 of the 18 pilot counties where early essential newborn care was implemented through the Safe Neonatal Project and 4 control counties not enrolled in Safe Neonatal Project were selected using purposive sampling. A total of 155 participants were interviewed, including stakeholders of the Safe Neonatal Project such as national maternal health experts, relevant government officials and medical staff. Thematic analysis was used to process and analyse the interview content in order to summarise the facilitators and barriers to implementing KMC. RESULTS: KMC was accepted in the pilot areas but still faced certain challenges due to institutional regulation, resource provision and the perceptions of health staff, postpartum mothers and their families as well as COVID-19 prevention and control regulations. The facilitators identified were government officials and medical staff acceptance and the incorporation of KMC into routine clinical care. The barriers identified were a lack of dedicated funding and other resources, the present scope of health insurance and KMC cost-sharing mechanism, providers' knowledge and practical abilities, parental awareness, postpartum discomfort, fathers' inadequate involvement, and the impact from COVID-19. CONCLUSION: The Safe Neonatal Project pilot experience indicated the feasibility of implementing KMC in more areas of China. Optimising institutional regulations, providing necessary supporting resources and enhancing education and training may help to refine the implementation and scale-up of KMC practice in China.