Long-read sequencing identifies novel structural variations in colorectal cancer.

Structural variations (SVs) are a key type of cancer genomic alterations, contributing to oncogenesis and progression of many cancers, including colorectal cancer (CRC). However, SVs in CRC remain difficult to be reliably detected due to limited SV-detection capacity of the commonly used short-read sequencing. This study investigated the somatic SVs in 21 pairs of CRC samples by Nanopore whole-genome long-read sequencing. 5200 novel somatic SVs from 21 CRC patients (494 SVs / patient) were identified. A 4.9-Mbp long inversion that silences APC expression (confirmed by RNA-seq) and an 11.2-kbp inversion that structurally alters CFTR were identified. Two novel gene fusions that might functionally impact the oncogene RNF38 and the tumor-suppressor SMAD3 were detected. RNF38 fusion possesses metastasis-promoting ability confirmed by in vitro migration and invasion assay, and in vivo metastasis experiments. This work highlighted the various applications of long-read sequencing in cancer genome analysis, and shed new light on how somatic SVs structurally alter critical genes in CRC. The investigation on somatic SVs via nanopore sequencing revealed the potential of this genomic approach in facilitating precise diagnosis and personalized treatment of CRC.

Logic Signal Amplification System for Sensitive Electrochemiluminescence Detection and Subtype Identification of Cancer Cells.

Achieving sensitive detection and accurate identification of cancer cells is vital for diagnosing and treating the disease. Here, we developed a logic signal amplification system using DNA tetrahedron-mediated three-dimensional (3D) DNA nanonetworks for sensitive electrochemiluminescence (ECL) detection and subtype identification of cancer cells. Specially designed hairpins were integrated into DNA tetrahedral nanostructures (DTNs) to perform a catalytic hairpin assembly (CHA) reaction in the presence of target microRNA, forming hyperbranched 3D nanonetworks. Benefiting from the "spatial confinement effect," the DNA tetrahedron-mediated catalytic hairpin assembly (DTCHA) reaction displayed significantly faster kinetics and greater cycle conversion efficiency than traditional CHA. The resulting 3D nanonetworks could load a large amount of Ru(phen)32+, significantly enhancing its ECL signal, and exhibit detection limits for both miR-21 and miR-141 at the femtomolar level. The biosensor based on modular logic gates facilitated the distinction and quantification of cancer cells and normal cells based on miR-21 levels, combined with miR-141 levels, to further identify different subtypes of breast cancer cells. Overall, this study provides potential applications in miRNA-related clinical diagnostics.

Endogenous AND Logic DNA Nanomachine for Highly Specific Cancer Cell Imaging.

Intracellular cancer-related biomarker imaging strategy has been used for specific identification of cancer cells, which was of great importance to accurate cancer clinical diagnosis and prognosis studies. Localized DNA circuits with improved sensitivity showed great potential for intracellular biomarkers imaging. However, the ability of localized DNA circuits to specifically image cancer cells is limited by off-site signal leakage associated with a single-biomarker sensing strategy. Herein, we integrated the endogenous enzyme-powered strategy with logic-responsive and localized signal amplifying capability to construct a self-assembled endogenously AND logic DNA nanomachine (EDN) for highly specific cancer cell imaging. When the EDN encountered a cancer cell, the overexpressed DNA repairing enzyme apurinic/apyrimidinic endonuclease 1 (APE1) and miR-21 could synergistically activate a DNA circuit via cascaded localized toehold-mediated strand displacement (TMSD) reactions, resulting in amplified fluorescence resonance energy transfer (FRET) signal. In this strategy, both endogenous APE1 and miR-21, served as two "keys" to activate the AND logic operation in cancer cells to reduce off-tumor signal leakage. Such a multiplied molecular recognition/activation nanomachine as a powerful toolbox realized specific capture and reliable imaging of biomolecules in living cancer cells.

Cancer-cell-specific Self-Reporting Photosensitizer for Precise Identification and Ablation of Cancer Cells.

Cancer-cell-specific fluorescent photosensitizers (PSs) are highly desired molecular tools for cancer ablation with minimal damage to normal cells. However, such PSs that can achieve cancer specification and ablation and a self-reporting manner concurrently are rarely reported and still an extremely challenging task. Herein, we have proposed a feasible strategy and conceived a series of fluorescent PSs based on simple chemical structures for identifying and killing cancer cells as well as monitoring the photodynamic therapy (PDT) process by visualizing the change of subcellular localization. All of the constructed cationic molecules could stain mitochondria in cancer cells, identify cancer cells specifically, and monitor cancer cell viability. Among these, IVP-Br has the strongest ability to produce ROS, which serves as a potent PS for specific recognition and killing of cancer cells. IVP-Br could translocate from mitochondria to the nucleolus during PDT, self-reporting the entire therapeutic process. Mechanism study confirms that IVP-Br with light irradiation causes cancer cell ablation via inducing cell cycle arrest, cell apoptosis, and autophagy. The efficient ablation of tumor through PDT induced by IVP-Br has been confirmed in the 3D tumor spheroid chip. Particularly, IVP-Br could discriminate cancer cells from white blood cells (WBCs), exhibiting great potential to identify circulating tumor cells (CTCs).

Interfacial Hydrogen-Bond Interactions Driven Assembly toward Polychromatic Copper Nanoclusters.

Constructing versatile metal nanoclusters (NCs) assemblies through noncovalent weak interactions between inter-ligands is a long-standing challenge in interfacial chemistry, while compelling interfacial hydrogen-bond-driven metal NCs assemblies remain unexplored so far. Here, the study reports an amination-ligand o-phenylenediamine-coordinated copper NCs (CuNCs), demonstrating the impact of interfacial hydrogen-bonds (IHBs) motifs on the luminescent behaviors of metal NCs as the alteration of protic solvent. Experimental results supported by theoretical calculation unveil that the flexibility of interfacial ligand and the distance of cuprophilic CuI···CuI interaction between intra-/inter-NCs can be tailored by manipulating the cooperation between the diverse IHBs motifs reconstruction, therewith the IHBs-modulated fundamental structure-property relationships are established. Importantly, by utilizing the IHBs-mediated optical polychromatism of aminated CuNCs, portable visualization of humidity sensing test-strips with fast response is successfully manufactured. This work not only provides further insights into exploring the interfacial chemistry of NCs based on inter-ligands hydrogen-bond interactions, but also offers a new opportunity to expand the practical application for optical sensing of metal NCs.

Dietary potential of the symbiotic fungus Penicillium herquei for the larvae of a nonsocial fungus-cultivating weevil Euops chinensis.

Many insect taxa cultivate fungi for food. Compared to well-known fungus cultivation in social insects, our knowledge on fungus cultivation in nonsocial insects is still limited. Here, we studied the nutritional potentials of the fungal cultivar, Penicillium herquei, for the larvae of its nonsocial insect farmer, Euops chinensis, a specialist on Japanese knotweed Reynoutria japonica. Overall, fungal hyphae and leaf rolls contained significantly higher carbon (C), stable isotopes of C (δ13C), and nitrogen (δ15N) but significantly lower C/N ratios compared to unrolled leaves, whereas insect bodies contained significantly higher N contents but lower C and C/N ratios compared to other types of samples. The MixSIAR model indicated that fungal hyphae contributed a larger proportion (0.626-0.797) to the diet of E. chinensis larvae than leaf materials. The levels of ergosterol, six essential amino acids, seven nonessential amino acids, and three B vitamins tested in fungal hyphae and/or leaf rolls were significantly higher than in unrolled leaves and/or larvae. The P. herquei genome contains the complete set of genes required for the biosynthesis of ergosterol, the essential amino acids valine and threonine, nine nonessential amino acids, and vitamins B2 and B3, whereas some genes associated with five essential and one nonessential amino acid were lost in the P. herquei genome. These suggest that P. herquei is capable of providing the E. chinensis larvae food with ergosterol, amino acids, and B vitamins. P. herquei appears to be able to synthesize or concentrate these nutrients considering that they were specifically concentrated in fungal hyphae. IMPORTANCE: The cultivation of fungi for food has occurred across divergent insect lineages such as social ants, termites, and ambrosia beetles, as well as some seldom-reported solitary insects. Although the fungal cultivars of these insects have been studied for decades, the dietary potential of fungal cultivars for their hosts (especially for those nonsocial insects) is largely unknown. Our research on the mutualistic system Euops chinensis-Penicillium herquei represents an example of the diverse nutritional potentials of the fungal cultivar P. herquei in the diet of the larvae of its solitary host, E. chinensis. These results demonstrate that P. herquei has the potential to synthesize or concentrate ergosterol, amino acids, and B vitamins and benefits the larvae of E. chinensis. Our findings would shed light on poorly understood fungal cultivation mutualisms in nonsocial insects and underscore the nutritional importance of fungal cultivars in fungal cultivation mutualisms.

Density Functional Theory Study on the Interaction between Aflatoxin B1/M1 and Gold Substrate.

Aflatoxin M1 (AFM1) and its precursor, Aflatoxin B1 (AFB1), are highly pathogenic and mutagenic substances, making the detection and sensing of AFB1/M1 a long-standing focus of researchers. Among various detection techniques, surface-enhanced Raman spectroscopy (SERS) is considered an ideal method for AFB1/M1 detection due to its ability not only to enhance characteristic frequencies but also to detect shifts in these frequencies with high repeatability. Therefore, we employed density functional theory in conjunction with surface-enhanced Raman spectroscopy to investigate the interaction between AFB1/M1 and a Au substrate in the context of the SERS effect for the first time. To predict the potential binding sites of AFB1/M1 and Au within the SERS effect, we performed calculations on the molecular electrostatic potential of AFB1/M1. Considering the crucial role of the binding energy in molecular docking studies, we computed the binding energy between two molecules interacting with Au at different binding sites. The molecular frontier orbitals and related chemical parameters of AFB1/M1 and "molecular-Au" complexes were computed to elucidate the alterations in AFB1/M1 molecules under the SERS effect. Subsequently, the theoretical Raman spectra of AFB1/M1 and the complexes were compared and analyzed, enabling determination of the adsorption conformation of AFB1/M1 on the gold surface based on SERS surface selection rules. These findings not only provide a deeper understanding of the interaction mechanism between molecules and substrates in the SERS effect but also offer theoretical support for developing novel aflatoxin SERS sensors.

Microfluidic chip immunoassay based on rolling circle amplification and G-quadruplex/Thioflavin T for multiplex detection of CTX I.

A label-free immunoassay based on rolling circle amplification (RCA) and G-quadruplex/Thioflavin T (G4/ThT) is proposed to realize the sensitive detection of carboxy-terminal cross-linked fragment of type I collagen (CTX I) for bone loss. Under the optimal conditions, as low as 38.02 pg/mL of CTX I can be detected. To improve the detecting throughput and simplify the operation, a microfluidic chip was designed, fabricated, and used for CTX I detection based on the proposed assay. The detection can be completed with only a single on-chip magnetic separation step, which was easy to operate, less time-consuming, and has only low reagent consumption. The limit of detection was 131.83 pg/mL by observing with fluorescence microscope. With further improvement of detection equipment, the sensitivity of on-chip detection can be improved. It can be expected that the proposed RCA/G4/ThT immunoassay for sensitive and high-throughput automated detection of CTX I might be chosen as a potential analytical tool for clinical osteoporosis diagnosis and in-orbit bone loss detection.

PltDB: a blood platelets-based gene expression database for disease investigation.

MOTIVATION: Molecular profiling of blood-based liquid biopsies is a promising disease detection method, which overcomes the limitations of invasive diagnostic strategies. Recently, gene expression profiling of platelets reportedly provides valuable resource for developing new biomarkers for the detection of diseases, including cancer. However, there is no database containing RNAs in platelets. RESULTS: In this study, we constructed PltDB (http://www.pltdb-hust.com), a blood platelets-based gene expression database featuring integration and visualization of RNA expression profiles based on RNA-seq and microarray data spanning both normal individuals and patients with different diseases. PltDB currently contains the expression landscape of mRNAs, lncRNAs, circRNAs and miRNAs in platelets from patients with different disease types and healthy controls. Moreover, PltDB provides users with the tools for visualizing results of comparison and correlation analysis and for downloading expression profiles and analysis results. A submission interface for the scientific community is also embraced for uploading novel RNA expression profiles derived from platelet samples. PltDB will offer a comprehensive review of the clinical use of platelets, overcome technical problems when analyzing data from diverse studies and serve as a powerful platform for developing new blood biomarkers. AVAILABILITY AND IMPLEMENTATION: PltDB is accessible at http://www.pltdb-hust.com. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Research progress on the therapeutic effects of nanoparticles loaded with drugs against atherosclerosis.

Presently, there are many drugs for the treatment of atherosclerosis (AS), among which lipid-lowering, anti-inflammatory, and antiproliferative drugs have been the most studied. These drugs have been shown to have inhibitory effects on the development of AS. Nanoparticles are suitable for AS treatment research due to their fine-tunable and modifiable properties. Compared with drug monotherapy, experimental results have proven that the effects of nanoparticle-encapsulated drugs are significantly enhanced. In addition to nanoparticles containing a single drug, there have been many studies on collaborative drug treatment, collaborative physical treatment (ultrasound, near-infrared lasers, and external magnetic field), and the integration of diagnosis and treatment. This review provides an introduction to the therapeutic effects of nanoparticles loaded with drugs to treat AS and summarizes their advantages, including increased targeting ability, sustained drug release, improved bioavailability, reduced toxicity, and inhibition of plaque and vascular stenosis.

Rapid automatic nucleic acid purification system based on gas-liquid immiscible phase.

The continuous expansion of nucleic acid detection applications has resulted in constant developments in rapid, low-consumption, and highly automated nucleic acid extraction methods. Nucleic acid extraction using magnetic beads across an immiscible phase interface offers significant simplification and parallelization potential. The gas-liquid immiscible phase valve eliminates the requirement for complicated cassettes and is suitable for automation applications. By analyzing the process of magnetic beads crossing the gas-liquid interface, we utilized a low magnetic field strength to drive large magnetic bead packages to cross the gas-liquid interface, providing a solution of high magnetic bead recovery rate for solid-phase extraction with a low-surfactant system based on gas-liquid immiscible phase valve. The recovery rate of magnetic beads was further improved to 90%-95% and the carryover of the reagents was below 1%. Consequently, a chip and an automatic system were developed to verify the applicability of this method for nucleic acid extraction. The Hepatitis B virus serum standard was used for the extraction test. The extraction of four samples was performed within 7 minutes, with nucleic acid recovery maintained above 80% and good purity. Thus, through analysis and experiments, a fast, highly automated, and low-consumption nucleic acid recovery method was proposed in this study.

A Comparative Study of the Typing Performance of Two Mid-Air Text Input Methods in Virtual Environments.

Inputting text is a prevalent requirement among various virtual reality (VR) applications, including VR-based remote collaboration. In order to eliminate the need for complex rules and handheld devices for typing within virtual environments, researchers have proposed two mid-air input methods-the trace and tap methods. However, the specific impact of these input methods on performance in VR remains unknown. In this study, typing tasks were used to compare the performance, subjective report, and cognitive load of two mid-air input methods in VR. While the trace input method was more efficient and novel, it also entailed greater frustration and cognitive workload. Fortunately, the levels of frustration and cognitive load associated with the trace input method could be reduced to the same level as those of the tap input method via familiarity with VR. These findings could aid the design of virtual input methods, particularly for VR applications with varying text input demands.

Polarization-insensitive coupled optoelectronic oscillator with low spurious tones and phase noise.

A coupled optoelectronic oscillator (COEO) based on σ-shaped fiber ring structure and intra-cavity semiconductor optical amplifier (SOA) is proposed and experimentally demonstrated. The σ-shaped fiber ring structure is skillfully utilized in COEO to eliminate the harmful influence of polarization disturbance. The SOA is embedded for super-mode suppression due to the fast gain saturation effect. The eximious phase noise performance of COEO could be maintained by operating the SOA at the unitary gain regime. The stable operation of COEO is guaranteed by the immunity to polarization fluctuation and the greatly suppressed spurious-mode competition. As a result, a 10-GHz signal is generated featuring high spectral purity and ultra-low spurious tones as soon as the system is power-on, and can hold steady even if the polarization changes dramatically. The single sideband phase noise of the proposed COEO is about -133 dBc/Hz at 10-kHz offset frequency, and the spurious suppression ratio reaches more than 95 dB, which is 60-dB superior than the conventional COEO.

E. coli biosensor based on modular GFP and luxI/luxR cyclic amplification circuit for sensitive detection of lysine.

In this study, an E. coli biosensor based on modular green fluorescent protein and luxI/IuxR cycle amplification circuit was constructed for sensitive detection of bioavailable lysine. The results indicated that the luxI/IuxR positive feedback circuit based on quorum sensing can be used as a signal amplifier to improve the sensitivity to lysine detection with the detection limit of 256 nM. The presented method was more sensitive than the previously reported whole-cell fluorescent microbial biosensors. In addition, the developed E. coli biosensor was specific for lysine detection, and other amino acids and proteins did not cause any interference. The constructed genetic engineered biosensor was accurate for lysine detection, the lysine content of 6.87 ± 0.36% in tryptone was successfully measured, and after adding 10, 30, and 50 µM lysine in tryptone, the recoveries of 109.98 ± 10.44%, 103.88 ± 7.66%, and 105.89 ± 6.34% were obtained, respectively. Furthermore, as the design of the genetic engineered biosensor is modular, it can conceivably be utilized as a component in the design of more complex synthetic gene circuits without any changes to the amplifier and reporter system.

Microfluidic chip-based long-term preservation and culture of engineering bacteria for DNA damage evaluation.

Understanding the effects of long-term exposure to space environment is paramount to maintaining the safety, health of astronauts. The physical dosimeters currently used on the space station cannot be used to assess the physiological effects of radiation. Moreover, some developed biological methods are time-consuming and passive and cannot be used for active and real-time detection of the physiological effects of radiation in space environment. Here, the SOS promoter: recA-eGFP genetic engineering bacteria was constructed and characterized, and DNA damage effects of some chemical reagents and radiation were evaluated. The results indicated the constructed engineering bacteria can distinguish DNA damage reagents from non-damage reagents and have a good dose-fluorescence effect against Co-60 radiation with the detection limit of 0.64 Gy; in order to overcome the restriction of long-term preservation of bacteria in space environment, the bacteria were freeze-dried, and the protectants were optimized, the storage time of bacteria under dry conditions was explored by accelerated storage experiment. Finally, a microfluidic chip was designed and fabricated for freeze-drying genetic engineering bacteria recovery, culture, and analysis in space environment. This study can provide support for the establishment of on-orbit radiation damage risk monitoring and early warning and can provide basic data for maintaining the health and performance of astronauts on long-term space flight missions. Moreover, the technique developed herein has a great potential to be used as a powerful tool for efficiently screening various radioactive substance, toxic chemicals, drugs, etc. KEY POINTS: • The SOS promoter: recA-eGFP genetic engineering bacteria was successfully constructed, which can distinguish DNA damage reagents from non-damage reagents and possess a good dose-effect relationship against Co-60 radiation. • The bacteria were freeze-dried to overcome the restriction of long-term preservation of bacteria in space environment, and protectants were optimized, and the survival rate of freeze-dried engineering bacteria can be predicted based on the results of accelerated storage experiment. • Microfluidic chip-based culture platform was successfully designed, fabricated, and used for freeze-drying genetic engineering bacteria recovery, culture, and analysis.

Perinatal Risks of Neonatal and Infant Mortalities in a Sub-provincial Region of China: A Livebirth Population-based Cohort Study.

BACKGROUND: Current vital statistics of birth population and neonatal outcome in China lacked information and definition of deaths at delivery and during hospitalization, especially for extreme preterm (EPT) birth. This study aims to delineate the prevalence of neonatal hospitalization, neonatal and infant mortality rates (NMR, IMR) and associated perinatal risks based on all livebirths in Huai'an, an evolving sub-provincial region in eastern China. METHODS: This retrospective cohort study established a comprehensive database linking information of whole regional livebirths and neonatal hospitalization in 2015, including deaths at delivery and EPT livebirths. The primary outcomes were NMR and IMR stratified by gestational age (GA) and birthweight (BW) with 95% confidence intervals. Causes of the neonatal and infant deaths were categorized according to the International Statistical Classification of Diseases 10th version, and population attributable fractions of GA and BW strata were analyzed. Perinatal risks of infant mortalities in continuum periods were estimated by Cox regression models. RESULTS: Among the whole livebirth population (59056), 7960 were hospitalized (prevalence 13.5%), with 168 (2.8‰) in-hospital deaths. The NMR was 3.6 (3.2, 4.1)‰ and IMR 4.9 (1.4, 4.5)‰, with additionally 35 (0.6‰) deaths at delivery. The major causes of infant deaths were perinatal conditions (2.6‰, mainly preterm-related), congenital anomalies (1.5‰), sudden unexpected death in infancy (0.6‰) and other causes (0.2‰). The deaths caused by preterm and low BW (LBW) accounted for 50% and 40% of NMR and IMR, with 20-30% contributed by EPT or extremely LBW, respectively. Multivariable Cox regression analysis revealed that peripartum factors and LBW strata had strong association with early- and late-neonatal deaths, whereas those of GA < 28 weeks were highly associated with postneonatal deaths. Congenital anomalies and neonatal hospitalization remained high death risks over the entire infancy, whereas maternal co-morbidities/complications were modestly associated with neonatal but not postneonatal infant mortality. CONCLUSIONS: The NMR, IMR, major causes of deaths and associated perinatal risks in continuum periods of infancy, denote the status and quality improvement of the regional perinatal-neonatal care associated with socioeconomic development. The study concept, applicability and representativeness may be validated in other evolving regions or countries for genuine comparison and better maternal-infant healthcare.

Flexible biochemical sensors for point-of-care management of diseases: a review.

Health problems have been widely concerned by all mankind. Real-time monitoring of disease-related biomarkers can feedback the physiological status of human body in time, which is very helpful to the diseases management of healthcare. However, conventional non-flexible/rigid biochemical sensors possess low fit and comfort with the human body, hence hindering the accurate and comfortable long-time health monitoring. Flexible and stretchable materials make it possible for sensors to be continuously attached to the human body with good fit, and more precise and higher quality results can be obtained. Thus, tremendous attention has been paid to flexible biochemical sensors in point-of-care (POC) for real-time monitoring the entire disease process. Here, recent progress on flexible biochemical sensors for management of various diseases, focusing on chronic and communicable diseases, is reviewed, and the detection principle and performance of these flexible biochemical sensors are discussed. Finally, some directions and challenges are proposed for further development of flexible biochemical sensors.

CAA-YOLO: Combined-Attention-Augmented YOLO for Infrared Ocean Ships Detection.

Infrared ocean ships detection still faces great challenges due to the low signal-to-noise ratio and low spatial resolution resulting in a severe lack of texture details for small infrared targets, as well as the distribution of the extremely multiscale ships. In this paper, we propose a CAA-YOLO to alleviate the problems. In this study, to highlight and preserve features of small targets, we apply a high-resolution feature layer (P2) to better use shallow details and the location information. In order to suppress the shallow noise of the P2 layer and further enhance the feature extraction capability, we introduce a TA module into the backbone. Moreover, we design a new feature fusion method to capture the long-range contextual information of small targets and propose a combined attention mechanism to enhance the ability of the feature fusion while suppressing the noise interference caused by the shallow feature layers. We conduct a detailed study of the algorithm based on a marine infrared dataset to verify the effectiveness of our algorithm, in which the AP and AR of small targets increase by 5.63% and 9.01%, respectively, and the mAP increases by 3.4% compared to that of YOLOv5.

Dual Recognition DNA Triangular Prism Nanoprobe: Toward the Relationship between K+ and pH in Lysosomes.

Lysosomal acidification is essential for its degradative function, and the flux of H+ correlated with that of K+ in lysosomes. However, there is little research on their correlation due to the lack of probes that can simultaneously image these two ions. To deeply understand the role of K+ in lysosomal acidification, here, we designed and fabricated a nanodevice using a K+-aptamer and two pH-triggered nanoswitches incorporated into a DNA triangular prism (DTP) as a dual signal response platform to simultaneously visualize K+ and pH in lysosomes by a fluorescence method. This strategy could conveniently integrate two signal recognition modules into one probe, so as to achieve the goal of sensitive detection of two kinds of signals in the same time and space, which is suitable for the detection of various signals with the correlation of concentration. By co-imaging both K+ and H+ in lysosomes, we found that the efflux of K+ was accompanied by a decrease of pH, which is of great value in understanding lysosomal acidification. Moreover, this strategy also has broad prospects as a versatile optical sensing platform for multiplexed analysis of other biomolecules in living cells.

A birth population-based survey of preterm morbidity and mortality by gestational age.

BACKGROUND: Despite 15-17 millions of annual births in China, there is a paucity of information on prevalence and outcome of preterm birth. We characterized the outcome of preterm births and hospitalized preterm infants by gestational age (GA) in Huai'an in 2015, an emerging prefectural region of China. METHODS: Of 59,245 regional total births, clinical data on 2651 preterm births and 1941 hospitalized preterm neonates were extracted from Huai'an Women and Children's Hospital (HWCH) and non-HWCH hospitals in 2018-2020. Preterm prevalence, morbidity and mortality rates were characterized and compared by hospital categories and GA spectra. Death risks of preterm births and hospitalized preterm infants in the whole region were analyzed with multivariable Poisson regression. RESULTS: The prevalence of extreme, very, moderate, late and total preterm of the regional total births were 0.14, 0.53, 0.72, 3.08 and 4.47%, with GA-specific neonatal mortality rates being 44.4, 15.8, 3.7, 1.5 and 4.3%, respectively. There were 1025 (52.8% of whole region) preterm admissions in HWCH, with significantly lower in-hospital death rate of inborn (33 of 802, 4.1%) than out-born (23 of 223, 10.3%) infants. Compared to non-HWCH, three-fold more neonates in HWCH were under critical care with higher death rate, including most extremely preterm infants. Significantly all-death risks were found for the total preterm births in birth weight <  1000 g, GA < 32 weeks, amniotic fluid contamination, Apgar-5 min < 7, and birth defects. For the hospitalized preterm infants, significantly in-hospital death risks were found in out-born of HWCH, GA < 32 weeks, birth weight <  1000 g, Apgar-5 min < 7, birth defects, respiratory distress syndrome, necrotizing enterocolitis and ventilation, whereas born in HWCH, antenatal glucocorticoids, cesarean delivery and surfactant use decreased the death risks. CONCLUSIONS: The integrated data revealed the prevalence, GA-specific morbidity and mortality rate of total preterm births and their hospitalization, demonstrating the efficiency of leading referral center and whole regional perinatal-neonatal network in China. The concept and protocol should be validated in further studies for prevention of preterm birth.