Yersinia ruckeri Infection and Enteric Redmouth Disease among Endangered Chinese Sturgeons, China, 2022.

During October 2022, enteric redmouth disease (ERM) affected Chinese sturgeons at a farm in Hubei, China, causing mass mortality. Affected fish exhibited characteristic red mouth and intestinal inflammation. Investigation led to isolation of a prominent bacterial strain, zhx1, from the internal organs and intestines of affected fish. Artificial infection experiments confirmed the role of zhx1 as the pathogen responsible for the deaths. The primary pathologic manifestations consisted of degeneration, necrosis, and inflammatory reactions, resulting in multiple organ dysfunction and death. Whole-genome sequencing of the bacteria identified zhx1 as Yersinia ruckeri, which possesses 135 drug-resistance genes and 443 virulence factor-related genes. Drug-susceptibility testing of zhx1 demonstrated high sensitivity to chloramphenicol and florfenicol but varying degrees of resistance to 18 other antimicrobial drugs. Identifying the pathogenic bacteria associated with ERM in Chinese sturgeons establishes a theoretical foundation for the effective prevention and control of this disease.

Neurotropin® ameliorates chronic pain associated with scar formation in a mouse model: A gene expression analysis of the inflammatory response.

Background: Scar formation after trauma and surgery involves an inflammatory response and can lead to the development of chronic pain. Neurotropin® (NTP) is a nonprotein extract of inflamed skin of rabbits inoculated with vaccinia virus. It has been widely used for the treatment of chronic pain. However, the in vivo effects of NTP on painful scar formation have not been determined. To investigate the molecular mechanisms underlying the effects of NTP on the inflammatory response, we evaluated gene expression in the scar tissues and dorsal root ganglions (DRGs) of mice administered NTP and control mice. Methods and results: Mice injected with saline or NTP were used as controls; other mice were subjected to surgery on the left hind paw to induce painful scar formation, and then injected with saline or NTP. Hind paw pain was evaluated by measuring the threshold for mechanical stimulation using the von Frey test. The paw withdrawal threshold gradually returned to pre-operative levels over 4 weeks post-operation; NTP-treated mice showed a significantly shortened recovery time of approximately 3 weeks, suggesting that NTP exerted an analgesic effect in this mouse model. Total RNA was extracted from the scarred hind paw tissues and DRGs were collected 1 week post-operation for a microarray analysis. Gene set enrichment analysis revealed that the expression of some gene sets related to inflammatory responses was activated or inhibited following surgery and NTP administration. Quantitative real-time reverse transcription-polymerase chain reaction analysis results for several genes were consistent with the microarray results. Conclusion: The administration of NTP to the hind paws of mice with painful scar formation following surgery diminished nociceptive pain and reduced the inflammatory response. NTP inhibited the expression of some genes involved in the response to surgery-induced inflammation. Therefore, NTP is a potential therapeutic option for painful scar associated with chronic pain.

Lignin-Based Nanoparticles for Combination of Tumor Oxidative Stress Amplification and Reactive Oxygen Species Responsive Drug Release.

In this study, maleic anhydride-modified lignin (LG-M), a ROS-cleavable thioketal (TK) bond, and polyethylene glycol (PEG) were used to synthesize a lignin-based copolymer (LG-M(TK)-PEG). Doxorubicin (DOX) was attached to the ROS-cleavable bond in the LG-M(TK)-PEG for the preparation of the ROS-activatable DOX prodrug (LG-M(TK-DOX)-PEG). Nanoparticles (NPs) with a size of 125.7 ± 3.1 nm were prepared by using LG-M(TK-DOX)-PEG, and they exhibited enhanced uptake by cancer cells compared to free DOX. Notably, the presence of lignin in the nanoparticles could boost ROS production in breast cancer 4T1 cells while showing little effect on L929 normal cells. This selective effect facilitated the specific activation of the DOX prodrug in the tumor microenvironment, resulting in the superior tumor inhibitory effects and enhanced biosafety relative to free DOX. This work demonstrates the potential of the LG-M(TK-DOX)-PEG NPs as an efficient drug delivery system for cancer treatment.

Changes in Microbial Composition During the Succession of Biological Soil Crusts in Alpine Hulun Buir Sandy Land, China.

Biological soil crusts (biocrusts) are considered "desert ecosystem engineers" because they play a vital role in the restoration and stability maintenance of deserts, including those cold sandy land ecosystems at high latitudes, which are especially understudied. Microorganisms participate in the formation and succession of biocrusts, contributing to soil properties' improvement and the stability of soil aggregates, and thus vegetation development. Accordingly, understanding the composition and successional characteristics of microorganisms is a prerequisite for analyzing the ecological functions of biocrusts and related applications. Here, the Hulun Buir Sandy Land region in northeastern China-lying at the highest latitude of any sandy land in the country-was selected for study. Through a field investigation and next-generation sequencing (Illumina MiSeq PE300 Platform), our goal was to assess the shifts in diversity and community composition of soil bacteria and fungi across different stages during the succession of biocrusts in this region, and to uncover the main factors involved in shaping their soil microbial community. The results revealed that the nutrient enrichment capacity of biocrusts for available nitrogen, total nitrogen, total phosphorus, total content of water-soluble salt, available potassium, soil organic matter, and available phosphorus was progressively enhanced by the succession of cyanobacterial crusts to lichen crusts and then to moss crusts. In tandem, soil bacterial diversity increased as biocrust succession proceeded but fungal diversity decreased. A total of 32 bacterial phyla and 11 fungal phyla were identified, these also known to occur in other desert ecosystems. Among those taxa, the relative abundance of Proteobacteria and Cyanobacteria significantly increased and decreased, respectively, along the cyanobacterial crust-lichen-moss crust successional gradient. However, for Actinobacteria, Chloroflexi, and Acidobacteria their changed relative abundance was significantly hump-shaped, increasing in the shift from cyanobacterial crust to lichen crust, and then decreasing as lichen crust shifted to moss crust. In this process, the improved soil properties effectively enhanced soil bacterial and fungal community composition. Altogether, these findings broaden our understanding about how soil microbial properties can change during the succession of biocrusts in high-latitude, cold sandy land ecosystems.

Propagation properties of a partially coherent electromagnetic hyperbolic-sine-Gaussian vortex beam through anisotropic atmospheric turbulence.

Using the extended Huygens-Fresnel principle and the Rytov approximation, the analytical formula for the propagation of a partially coherent electromagnetic hyperbolic-sine-Gaussian vortex beam (PCEShVB) in anisotropic atmospheric turbulence has been theoretically derived. Detailed studies have been conducted on the evolution characteristics of the average intensity, the degree of coherence (DOC), and the degree of polarization (DOP) of the beam in turbulence. The results show that during propagation, the intensity distribution of the beam will exhibit a spiral structure, and the overall distribution of the light spots will rotate in a direction related to the sign of the topological charge. The DOC distribution of PCEShVB will display a pattern reminiscent of beam interference fringes with an increase in propagation distance, with the number of "interference fringes" greatly impacted by the hyperbolic sine parameter. Furthermore, PCEShVB with a large initial coherent length and hyperbolic sine parameter will increase the degree of separation of the spots and yield a large DOP. Finally, for the validation of the theoretical findings, the random phase screen method was employed to simulate the propagation of PCEShVB through anisotropic atmospheric turbulence. The studies revealed a consistent alignment between the simulation results and the theoretical predictions.

[Huaier triggering mitochondria apoptosis in colorectal cancer cells through oxidative stress].

This study investigates the specific mechanisms of Huaier-induced mitochondrial apoptosis in colorectal cancer. HCT116 and SW480 cells were subjected to Huaier treatment. Cell proliferation and migration capabilities were examined through CCK-8 and scratch experiments, respectively. Apoptotic cells were clarified with Annexin-PE staining. DCFH-DA staining, malondialdehyde(MDA), and glutathione(GSH) were used to evaluate the oxidative stress damage level of cells. MitoSOX and JC-1 probes were used to selectively target mitochondria reactive oxygen species(mtROS) and mitochondria membrane potential(MMP) for the evaluation of mitochondria damage. Western blot(WB) experiment was performed to determine apoptosis proteins and PINK1/Parkin pathway. Experiments reveal that in different concentrations of Huaier treatment, the proliferation and migration capabilities of HCT116 and SW480 cells were both restrained. Additionally, mitochondrial apoptosis was activated. Compared with the control group, excessive ROS in colorectal cancer cells was generated in the Huaier group, while MDA increased, and GSH decreased, indicating oxidative stress damage. mtROS increased, and MMP decreased in colorectal cancer cells treated with Huaier, indicating mitochondrial damage. WB result revealed that Huaier suppressed the PINK1/Parkin pathway, hindered the clearance of impaired mitochondria, and subsequently facilitated apoptosis. In conclusion, Huaier impairs colorectal cancer cells through oxidative stress and mitochondria damage. Furthermore, it suppressed the PINK1/Parkin pathway, promoting mitochondria apoptosis in colorectal cancer cells.

Nickel-Catalyzed Regio- and Enantioselective Borylative Coupling of Terminal Alkenes with Alkyl Halides Enabled by an Anionic Bisoxazoline Ligand.

Chiral boronic esters are a class of versatile building blocks. We describe herein an asymmetric nickel-catalyzed borylative coupling of terminal alkenes with nonactivated alkyl halides. The success of this asymmetric reaction is ascribed to the application of a chiral anionic bisoxazoline ligand. This study provides a three-component strategy to access α- and ß-stereogenic boronic esters from easily accessible starting materials. This protocol is characterized by mild reaction conditions, wide substrate scope and high regio- and enantioselectivity. We also showcase the value of this method in simplifying the synthesis of several drug molecules. Mechanistic studies suggest that the generation of enantioenriched boronic esters bearing an α-stereogenic center results from a stereoconvergent process, while the enantioselectivity-controlling step in the generation of boronic esters with a ß-stereocenter is switched to the olefin migratory insertion step due to coordination of an ester group.

Building Porous Ni(Salen)-Based Catalysts from Waste Styrofoam via Autocatalytic Coupling Chemistry for Heterogeneous Oxidation with Molecular Oxygen.

The development of robust and industrially viable catalysts from plastic waste is of great significance, and the facile construction of high performance heterogeneous catalyst systems for phenol-quinone conversions remains a grand challenge. Herein, a feasible strategy is demonstrated to reclaim Styrofoam into hierarchically porous nickel-salen-loaded hypercrosslinked polystyrene (PS@Ni-salen) catalysts with high activities through an unusual autocatalytic coupling route. The salen is immobilized onto PS chain by Friedel-Crafts alkylation of benzyl chloride derivatives, and the generated hydrogen chloride coordinately promotes the simultaneous crosslinking and bridge formation between aromatic rings via a Scholl coupling route, leading to hierarchically porous networks. After the metallization with Ni, the resultant networks exhibit high catalytic activity for the oxidation of 2,3,6-trimethylphenol to 2,3,5-trimethyl-1,4-benzoquinone under mild conditions (303 K, 1 bar of O2 ). This catalyst also demonstrates attractive recycling performance without an obvious loss of catalytic efficiency over five consecutive cycles. This methodology might provide a potential sustainable alternative to construct environmentally benign and cost-effective catalysts for specific organic transformation.

Distribution of cardiorespiratory fitness in children and adolescents at different latitudes.

OBJECTIVE: To explore the differences and characteristics of cardiorespiratory fitness (CRF) among children and adolescents in regions with different latitudes in China. METHODS: A total of 9892 children and adolescents aged 7-22 years were selected from seven administrative regions in China by the stratified cluster random sampling method. CRF was measured by performance on the 20 m shuttle run test (20mSRT) and estimated maximal oxygen consumption (VO2max ). One-way ANOVA, one-way ANCOVA, and the Lambda Mu and Sigma methods were used to analyze the data. RESULTS: Overall, the VO2max of children and adolescents at high latitudes was significantly lower than that of children at low and middle latitudes. The P10 , P50 , and P90 20mSRT values for children and adolescents of most age groups in high latitudes were less than those in low and middle latitudes. The 20mSRT-Z and VO2max -Z scores among children and adolescents aged 7-22 in high latitudes were lower than those in middle and low latitudes after adjusting for age, per capita gross domestic product (GDP), and per capita disposable income. CONCLUSION: In general, the CRF of children and adolescents at high latitudes was less than that at low and middle latitudes. Effective measures should be taken to improve CRF in children and adolescents at high latitudes.

Base-Modulated 1,3-Regio- and Stereoselective Carboboration of Cyclohexenes.

While chain-walking stimulates wide interest in both polymerization and organic synthesis, site- and stereoselective control of chain-walking on rings is still a challenging task in the realm of organometallic catalysis. Inspired by a controllable chain-walking on cyclohexane rings in olefin polymerization, we have developed a set of chain-walking carboborations of cyclohexenes based on nickel catalysis. Different from the 1,4-trans-selectivity disclosed in polymer science, a high level of 1,3-regio- and cis-stereoselectivity is obtained in our reactions. Mechanistically, we discovery that the base affects the reduction ability of B2 pin2 and different bases lead to different catalytic cycles and different regioselective products (1,2- Vs 1,3-addition). This study provides a concise and modular method for the synthesis of 1,3-disubstituted cyclohexylboron compounds. The incorporation of a readily modifiable boronate group greatly enhances the value of this method, the synthetic potential of which was highlighted by the synthesis of a series of high-valued commercial chemicals and pharmaceutically interesting molecules.

Modular and Facile Access to Chiral α-Aryl Phosphates via Dual Nickel- and Photoredox-Catalyzed Reductive Cross-Coupling.

Chiral phosphine-containing skeletons are important motifs in bioactive natural products, pharmaceuticals, chiral catalysts, and ligands. Herein, we report a general and modular platform to access chiral α-aryl phosphorus compounds via a Ni/photoredox-catalyzed enantioconvergent reductive cross-coupling between α-bromophosphates and aryl iodides. This dual catalytic regime exhibited high efficiency and good functional group compacity. A wide variety of substrates bearing a diverse set of functional groups could be converted into chiral phosphates in good to excellent yields and enantioselectivities. The utility of the method was also demonstrated by the development of a new phosphine ligand and the synthesis of enzyme inhibitor derivatives. The detailed mechanistic studies supported a radical chain process and revealed a unique distinction compared with traditional reductive cross-coupling.

Roles of age, sex, and weight status in the muscular fitness of Chinese Tibetan children and adolescents living at altitudes over 3600 m: A cross-sectional study.

OBJECTIVE: This study aimed to assess the role of age, sex, and weight status in the development of muscular fitness in a large sample of Chinese Tibetan children and adolescents aged 7-18 years living in areas over 3600 m. METHOD: A sample of 4673 Chinese Tibetan children and adolescents aged 7-18 years were recruited from 21 schools in three cities (Lhasa, Naqu, and Anduo) of Tibet, China. Grip strength, standing long jump, 30-s sit-ups, and 50-m dash were conducted to determine muscular fitness. Independent sample t tests were conducted to compare muscular fitness between boys and girls for each age group. The changes in mean scores on each muscular fitness test were estimated. The influence of weight status on muscular strength level was also estimated using one-way ANOVA and LSD tests. We also compared the average muscular fitness between Chinese Tibetan and Chinese average level. RESULTS: The muscular fitness of Chinese Tibetan boys aged 7-18 years was higher than that of girls, with older children outperforming younger children. Among the Chinese Tibetan boys, those in the normal-weight group showed the best performance, whereas overweight group showed the best performance among the girls. The performance of Chinese Tibetan children and adolescents in standing long jump and 50-m dash was lower while that in sit-ups was higher than the performance of their Chinese counterparts. CONCLUSION: Chinese Tibetan children and adolescents have relatively strong abdominal strength, but lower limb strength, which needs to be improved. Age, sex, and weight status should be considered when designing interventions to improve muscular fitness.

Significant genes in response to low temperature in Fenneropenaeus chinensis screened through multiple transcriptome group comparisons.

Fenneropenaeus chinensis is a migratory marine species with a suitable growth at 18-30°C. To prolong breeding season and reduce mortality in winter, breeding new shrimp varieties with cold tolerance is essential. Genes upregulated and highly expressed at low temperature are reasonable candidate genetic markers for the breeding of cold tolerant strain variants. This study screened genes with these features by comparing multiple low-vs. normal-temperature transcriptome groups. The results showed that nine genes were upregulated and highly expressed at low temperature in more than seven of the nine comparison groups. Six of them were identified as genes encoding transcription factor ATF2, RNA recognition motif domain-containing protein, cytochrome b5-like protein, troponin C, tubulin alpha-1, and 18S/5.8S/28S rRNA, respectively. Cold-inducible upregulations of ATF2, cytochrome b5, and rRNAs were novel findings in this study. The other three novel genes were predicted to encode a membrane-bound extracellular protein and two lncRNAs. Four of the screened genes were verified by real time RT-PCR, and their expression levels were consistent with the sequencing results, demonstrating the accuracy of the transcriptome sequencing data. Function analysis showed that ATF2 might be the master transcription factor regulating the expressions of proteins involved in cellular responses to cold. The other genes played a role in events such as enhancing translation, increasing energy, inhibiting apoptosis, and preserving cell integrity. The expression features of these nine genes suggested that they were of great significance to the cold tolerance of shrimp.

Relationship between waist circumference and cardiorespiratory fitness in Chinese children and adolescents: Results from a cross-sectional survey.

BACKGROUND: This article assessed the relationship between waist circumference (WC) and cardiorespiratory fitness (CRF) of children and adolescents aged 7-18 years. METHODS: Using a stratified cluster random sampling method, 92,574 children and adolescents (47,364 males and 45,210 females) were extracted. CRF was measured by performance in the 20 m shuttle run test (20mSRT) and the subsequent estimation of maximal oxygen consumption ( V ˙ O2max) using the Léger equations. Participants were divided into five groups of WC percentiles and three groups of CRF percentiles by the Lambda Mu Sigma (LMS). The correlation between WC and CRF was examined by one-way ANOVA and curvilinear regression analysis. RESULTS: WC increased with age, while V ˙ O2max showed an age-related decline. Controlling for gender, urban, and rural factors, for children and adolescents aged 10-12, 13-15, and 16-18 years, the V ˙ O2max Z-score of the normal WC group was significantly higher than the very low WC group (P < 0.05). Controlling for gender, urban, and rural factors, for participants aged 7-18 years, the V ˙ O2max Z-score of the normal WC group was significantly higher than the high WC group and the very high WC group (P < 0.05). CONCLUSIONS: It generally shows a "parabolic" trend between WC-Z and V ˙ O2max-Z. The CRF among children and adolescents in the normal WC group is significantly higher than that in the low and the high WC groups.

Practical Synthesis of Chiral Allylboronates by Asymmetric 1,1-Difunctionalization of Terminal Alkenes.

We report herein a modular catalytic method for the efficient enantioselective synthesis of chiral allylboronates from abundant feedstock chemicals through an asymmetric 1,1-difunctionalization of alkenes. This protocol is distinguished by its use of an inexpensive chiral catalyst, mild and convenient reaction conditions, wide substrate scope, scalability and practicality. The utility of this method is demonstrated by the rapid synthesis of key intermediates of complex drug molecules. Mechanistic studies reveal that ß-H elimination is a highly regioselective step and the reversible homolysis and convergance to the lower energy pre-reductive elimination intermediate is the enantio-determining step.

Design of ultrasonic standing wave levitation support for three-dimensional printed filaments.

Fused deposition modeling (FDM) three-dimensional (3D) printing is the process of forming a part by depositing molten thermoplastic materials layer by layer. Support structures need to be added below the overhangs or bridges in 3D printing. This paper proposes an idea for support-free FDM printing by studying the method of filament levitation. In this paper, an ultrasonic phased array device is designed, and different slender objects with length much longer than the sound wavelength are levitated in the air by multiple standing wave points. Experiments show that slender objects can be stably held at the sound pressure nodes in the standing wave field. After adding the ultrasonic field in FDM printing, the maximum deformation of single filament due to gravity on the bridge structure decreases from 5 to 2 mm. This proves that it is feasible for an ultrasonic phased array system to play an important role in the field of support-free FDM printing.

Relationship between cardiorespiratory fitness and latitude in children and adolescents: Results from a cross-sectional survey in China.

BACKGROUND: This study assessed the correlation between latitude and the cardiorespiratory fitness (CRF) of children and adolescents. METHODS: In 16 provinces and autonomous regions in China, 25,941 children and adolescents aged 10-18 were included. CRF was measured using the 20 m shuttle run test (20 m SRT) and estimated peak oxygen uptake (VO2peak). One-way ANOVA and multiple regression analysis were used to explore the correlation between CRF and latitude in children and adolescents. RESULTS: The VO2peak values of the low (south), middle, and high (north) latitude groups for boys were 43.1, 43.1, and 40.7 mL/kg/min, respectively, and 40.0, 40.0, and 38.5 mL/kg/min for girls, respectively. After adjusting for confounding factors, the regression coefficients (ß) between VO2peak-Z and both latitude-Z and (latitude-Z)2 for boys were -0.151 and -0.043, respectively. For girls, they were -0.142 and -0.020, respectively. The Partial correlation coefficient (r) for latitude-Z and (latitude-Z)2 were -0.14 and -0.04 for boys, and -0.13 and -0.02 for girls, respectively. CONCLUSION: The CRF among children and adolescents in high latitude regions is significantly lower than that in middle and low latitude region, and it generally shows a "parabolic" trend between Latitude-Z and VO2peak-Z.

Nomograms for prediction of overall and cancer-specific survival in young breast cancer.

PURPOSE: To assess the prognostic risk factors and establish prognostic nomograms based on lymph node ratio (LNR) to predict the survival of young patients with breast cancer (BC). METHODS: Patients aged < 40 years and diagnosed with BC between 2010 and 2016 from the Surveillance, Epidemiology and End Results database were assessed. Nomograms incorporating LNR were constructed to predict overall survival (OS) and breast cancer-specific survival (BCSS) based on Cox proportional hazards model. The performance of the nomograms was assessed by C-index, calibration curves, receiver operating characteristic (ROC) curves, decision curve analysis (DCA), and risk group stratification and compared with the TNM staging system. RESULTS: Based on the univariate and multivariate Cox regression analysis, significant prognostic factors were identified and integrated to create the nomograms for OS and BCSS. The calibration curves indicated optimal agreement between model predictions and actual observations. The nomograms showed favorable sensitivity with a C-index of 0.8351 (95% CI 0.8234-0.8469) for OS and 0.8474 (95% CI 0.8355-0.8594) for BCSS. The ROC curves of the nomograms showed better predictive ability than those of the TNM staging system for OS (AUC: 0.8503 vs. 0.7819) and BSCC (AUC: 0.8607 vs. 0.8081). Significant differences in Kaplan-Meier curves were observed in patients stratified into different risk groups (p < 0.001). CONCLUSIONS: These nomograms provided more accurate individualized risk prediction of OS and BCSS and may assist clinicians in making decisions for young patients with BC.

Role of SSH1 in colorectal cancer prognosis and tumor progression.

BACKGROUND AND AIM: Slingshot 1 protein (SSH1) plays a critical role in cytoskeleton dynamic regulation. Increasing evidence suggest that SSH1 expression is upregulated in several cancers and relates to tumor progression and drug resistance. Here, we evaluated the role of SSH1 in colorectal cancer (CRC) development and its prognostic value in patients with CRC. METHODS: SSH1 expression was examined by quantitative real-time polymerase chain reaction, western blot analysis, or immunohistochemistry. The association between SSH1 expression and clinical characteristics and prognosis was evaluated. Stable SSH1 knockdown cells were used for in vitro assays and xenograft models. Correlation between SSH1 expression and epithelial-mesenchymal transition (EMT) was analyzed by western blot and online data analysis. RESULTS: SSH1 expression was upregulated in cancer tissue compared with paired non-cancerous tissue in patients with CRC. SSH1 expression level in CRC tissue was associated with tumor stage, lymph node metastasis, and correlated with poor prognosis as indicated by univariate and multivariate analyses. In vitro, loss of SSH1 impaired colony formation, migration, and invasion of CRC cells. In vivo data suggest that SSH1 could promote the progression and metastasis of CRC. Interestingly, E-cadherin, ZEB1, and Snail, which are markers of EMT, had a significant expression correlation with SSH1. CONCLUSIONS: SSH1 expression is associated with CRC progression and predicts poor prognosis. SSH1 may promote CRC tumor progression by regulating EMT.

The Main Bottleneck for Non-Metastatic Pancreatic Adenocarcinoma in Past Decades: A Population-Based Analysis.

BACKGROUND Despite recent advancements in surgical techniques, chemotherapy, and radiotherapy, the 5-year survival rate of patients with pancreatic ductal adenocarcinoma (PDAC) remains an unsatisfactory ~8%. MATERIAL AND METHODS Data were extracted to identify patients with non-metastatic pancreatic adenocarcinoma diagnosed in the periods 1988-1996 and 2010-2014 in the Surveillance, Epidemiology, and End Results (SEER) database. The statistical analyses were performed with the log-rank test, Pearson's chi-square test, propensity score matching, and Cox regression model. RESULTS The hazard ratio (HR) of surgery was reduced from 0.454 to 0.302 in Cox regression modeling, and there was no overlapping about the 95% confidence intervals (CI) of surgery between the 2 periods. The HR values of radiotherapy, which were new prognostic factor for resectable PDAC in 2010-2014, were reduced in both the resectable and unresectable groups. The upgraded chemotherapy regimen reduced the HR values from 0.738 to 0.689 in all PADC patients, and from 0.656 to 0.588 in unresectable PDAC. The log-rank test results showed that advances in surgery significantly improved the median survival from 13 months to 32 months. Radiotherapeutic and chemotherapeutic advancements extended median survival by 12 months and 11 months, respectively, in resectable PDAC. The median survivals were extended by 3 months for both of radiotherapy and chemotherapy in unresectable PDAC. CONCLUSIONS The development of chemotherapy and radiotherapy has been slow, especially for unresectable PDAC. Although advances in surgery contributed significantly to improved survival for resectable PDAC, lack of early diagnostic tools, which lead to low resection rates, remain a barrier for all PDAC patients.