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Bingyuan Fei,1,* Zhanhao Mo,2,* Jinghui Yang,3 Zheng Wang,4 Shuo Li3 1Department of Gastrointestinal Colorectal Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People’s Republic of China; 2Department of Radiology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People’s Republic of China; 3Department of Hepatobiliary and Pancreatic Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People’s Republic of China; 4CAS Key Laboratory of Nano-Bio Interface Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shuo Li, Department of Hepatobiliary and Pancreatic Surgery, China-Japan Union Hospital of Jilin University, Changchun, 130033, People’s Republic of China, Email lishuo0609@jlu.edu.cn Zheng Wang, CAS Key Laboratory of Nano-Bio Interface Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, Jiangsu, 215123, People’s Republic of China, Email zwang2021@sinano.ac.cnBackground: The failure of cancer photodynamic therapy (PDT) is largely ascribed to excessive stroma and defective vasculatures that restrain the photosensitizer permeation and the oxygen perfusion in tumors.Method and Results: In this study, a nanodrug that integrated the cancer-associated fibroblast (CAF) regulation with tumor vessel normalization was tailored to sequentially sensitize PDT. The nanodrug exhibited high targeting towards CAFs and efficiently reversed the activated CAFs into quiescence, thus decreasing collagen deposition in the tumor microenvironment (TME), which overcame the protective physical barrier. Furthermore, the nanodrug regulated vascular endothelial cells and restored the tumor vasculatures, thereby improving vascular permeability. Based on the combined effects of reprogramming the TME, the nanodrug improved tumor accumulation of photosensitizers and alleviated hypoxia in the TME, which facilitated the subsequent PDT. Importantly, the nanodrug regulated the immunosuppressive TME by favoring the infiltration of immunostimulatory cells over immunosuppressive cells, which potentiated the PDT-induced immune response.Conclusion: Our work demonstrates a sequential treatment strategy in which the combination of the CAF regulation and tumor vasculature normalization, followed by PDT, could be a promising modality for sensitizing tumor to PDT.Keywords: tumor microenvironment, cancer-associated fibroblast, tumor vessel, photodynamic therapy, sequential treatments

Xiaobo Zhang, Ying Zhu, Ying Zhou, Bingru Fei Nephrology Department, The Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical University, Huaian, Jiangsu Province 223300, People’s Republic of ChinaCorrespondence: Xiaobo ZhangThe Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical University, Number 1 Huanghe Xi Lu, Huaiyin District, Huaian, Jiangsu Province 223300, People’s Republic of ChinaEmail zhangxiaobo2020@yeah.netObjective: Renal ischemia/reperfusion (I/R) injury is commonly seen in diabetic patients. Apelin has been demonstrated to protect against renal I/R injury, whereas detailed modulatory mechanisms by which Apelin exerts its role in renal I/R injury in diabetic patients remain unclarified. This research aimed to probe the functional molecules under the regulation of Apelin in renal I/R injury in diabetic rats.Materials and Methods: First, animal models were established for subsequent assays. Biochemical kits measured the serum levels of blood urea nitrogen (BUN) and serum creatinine (SCR), and hematoxylin and eosin (H&E) staining examined the histopathological changes of kidney tissues. Inflammatory factors containing tumor necrosis factor alpha (TNF-α), interleukin 1β (IL-1β), interleukin 6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) were tested through enzyme-linked immunosorbent assay (ELISA) and reverse transcription-quantitative polymerase chain reaction (RT-qPCR), respectively. Reactive oxygen species (ROS) levels in the serum and kidney tissues were separately assessed by specific ROS kits. Cell apoptosis was further estimated through terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and Western blot analysis. Eventually, the influences of Apelin on nuclear factor erythroid 2-related factor (Nrf2) and its downstream genes were explored via Western blot analysis and immunohistochemistry (IHC).Results: In the present study, Apelin ameliorated the damage to renal function and histological structure, decreased levels of inflammatory factors and ROS, and hampered cell apoptosis in renal I/R injury of diabetic rats. Moreover, Apelin could elevate the levels of Nrf2 and downstream genes which were decreased under renal I/R injury.Conclusion: These data indicated that Apelin inhibited renal I/R injury through regulating Nrf2 signaling in diabetic rats, which might shed new light on the treatment of renal I/R injury in diabetic patients.Keywords: renal ischemia/reperfusion injury, diabetes, Apelin, Nrf2 signaling

Zhuo Liu,1 Miao Yu,1 Bingyuan Fei,1 Jing Sun,2 Dongxin Wang3 1Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People’s Republic of China; 2Department of Biochemistry and Molecular Medicine, The George Washington University, Washington, DC, USA; 3Department of Anesthesiology, Jilin Cancer Hospital, Jilin, People’s Republic of ChinaCorrespondence: Dongxin WangDepartment of Anesthesiology, Jilin Cancer Hospital, 1018 Huguang Road, Changchun, Jilin 130031, People’s Republic of ChinaTel +86 139 4487 2227Email dongxingwang759@163.comPurpose: A previous study has identified that XRCC4-like factor (XLF) is a potential target to overcome resistance to 5-fluorouracil (5-Fu) and oxaliplatin (OXA) in colorectal cancer (CRC). The purpose of this study is to develop potent XLF inhibitors to chemoresistance in CRC.Methods: Virtual screening was adopted to identify novel XLF-binding compounds by initially testing 6800 molecules in Chemical Entities of Biological Interest library. Hit compounds were further validated by Western blot assay. Cell sensitivity to 5-Fu and OXA was measured using sulforhodamine B assay. The effect of XLF inhibitor on DNA repair efficiency was evaluated by comet assay, fluorescent-based nonhomologous end joining (NHEJ) and homologous recombination (HR) reporter assays. DNA-binding activity of NHEJ key factors was examined by chromatin fractionation assay.Results: We identified G3, a novel and potent XLF inhibitor (IC50 0.47±0.02 μM). G3 induced XLF protein degradation in CRC cells. Significantly, G3 improved cell sensitivity to 5-Fu and OXA in chemoresistant CRC cell lines. Mechanistically, G3 depleted XLF expression, severely compromised NHEJ efficiency by up to 65% and inhibited NHEJ key factor assembly on DNA. G3 also inhibited HR efficiency in a time-dependent manner.Conclusion: These results suggest that G3 overcomes 5-Fu and OXA resistance in CRC cells by inhibiting XLF expression. Thus, XLF is a promising target and its inhibitor G3 is a potential candidate for treatment of chemoresistant CRC patients.Keywords: virtual screening, XLF inhibitor, chemoresistance, colorectal cancer

Zhuo Liu,1 Miao Yu,1 Bingyuan Fei,1 Jing Sun,2 Dongxin Wang3 1Department of Gastrointestinal Colorectal and Anal Surgery, China–Japan Union Hospital of Jilin University, Changchun, Jilin 130021, China; 2Department of Biochemistry and Molecular Medicine, The George Washington University, Washington, DC 20052, USA; 3Department of Anesthesiology, Jilin Cancer Hospital, Changchun, Jilin 130021, China Background: Colorectal cancer (CRC) is the third commonly diagnosed cancer with a high risk of death. After curative surgery, 40% of patients will have metastases or develop recurrence. Therefore, chemotherapy is significantly responsible as the major therapy method. However, chemoresistance is found in almost all metastatic patients and remains a critical obstacle to curing CRC.Materials and methods: Cell viability is analyzed by sulforhodamine B staining assay. The nonhomologous end joining (NHEJ) repair ability of each cell line was determined by NHEJ reporter assay. mRNA expression levels of NHEJ factors are detected by real-time quantitative polymerase chain reaction. The protein expression levels were observed by western blot assay.Results: Our study found that 5-florouracil (5-Fu) and oxaliplatin (OXA)-resistant HCT116 and LS174T cells showed upregulated efficiency of DNA double-strand repair pathway NHEJ. We then identified that the NHEJ key factor XLF is responsible for the chemoresistance and XLF deficiency sensitizes CRC cells to 5-Fu and OXA significantly.Conclusion: Our research first demonstrates that the NHEJ pathway, especially its key factor XLF, significantly contributes to chemoresistance in CRC. Keywords: XLF, nonhomologous end joining, 5-florouracil, oxaliplatin, chemoresistance, colorectal cancer

Abstract Cellulose-degrading microorganisms hold immense significance in utilizing cellulose resources efficiently. The screening of natural cellulase bacteria and the optimization of fermentation conditions are the hot spots of research. This study meticulously screened cellulose-degrading bacteria from mixed soil samples adopting a multi-step approach, encompassing preliminary culture medium screening, Congo red medium-based re-screening, and quantification of cellulase activity across various strains. Particularly, three robust cellulase-producing strains were identified: A24 (MT740356.1 Brevibacillus borstelensis), A49 (MT740358.1 Bacillus cereus), and A61 (MT740357.1 Paenibacillus sp.). For subsequent cultivation experiments, the growth curves of the three obtained isolates were monitored diligently. Additionally, optimal CMCase production conditions were determined, keeping CMCase activity as a key metric, through a series of single-factor experiments: agitation speed, cultivation temperature, unit medium concentration, and inoculum volume. Maximum CMCase production was observed at 150 rpm/37 °C, doubling the unit medium addition, and a 5 mL inoculation volume. Further optimization was conducted using the selected isolate A49 employing response surface methodology. The software model recommended a 2.21fold unit medium addition, 36.11 °C temperature, and 4.91 mL inoculant volume for optimal CMCase production. Consequently, three parallel experiments were conducted based on predicted conditions consistently yielding an average CMCase production activity of 15.63 U/mL, closely aligning with the predicted value of 16.41 U/mL. These findings validated the reliability of the model and demonstrated the effectiveness of optimized CMCase production conditions for isolate A49.

The primary cause of high carbon emissions due to inefficient transportation is the lack of cooperation among various logistics companies during distribution. Joint distribution mode represents an effective means to address this issue. However, research on the joint distribution mode primarily focuses on the centralized joint distribution mode. In the context of the decentralized joint distribution mode, logistics companies can autonomously choose their distribution routes based on the orders they are dispatched. If logistics companies unilaterally aim to reduce their own costs, it can easily lead to an increase in carbon emissions from the alliance, which can have adverse effects. This paper focuses on the decentralized joint distribution alliance and considers reducing carbon emissions through the allocation of the alliance’s order. A two-stage approach is proposed, based on routing optimization and worst-case estimation. The mathematical models for each stage are established and algorithms are designed. Subsequently, management recommendations are provided through numerical analysis. This paper aims to explore methods to address the challenges faced by decentralized joint distribution alliances.

Abstract Background Human milk fortifier (HMF) composition has been optimized recently. But clinical evidence of its safety and efficacy is limited in Chinese population. The aim of this study was to evaluate effects of a new HMF in growth, nutritional status, feeding intolerance, and major morbidities among very preterm (VPT) or very low birth weight (VLBW) infants in China. Methods VPT/VLBW infants admitted from March 2020 to April 2021 were prospectively included in the experimental (new HMF, nHMF) group, who received a new powdered HMF as a breast milk feeding supplement during hospitalization. Infants in the control group (cHMF) admitted from January 2018 to December 2019, were retrospective included, and matched with nHMF group infants for gestational age and birth weight. They received other kinds of commercially available HMFs. Weight gain velocity, concentrations of nutritional biomarkers, incidence of major morbidities, and measures of feeding intolerance were compared between the two groups. Results Demographic and clinical characteristics of infants in nHMF and cHMF groups were comparable. Weight gain velocity had no significant difference between the nHMF (14.0 ± 3.5 g/kg/d) and the cHMF group (14.2 ± 3.8 g/kg/d; P = 0.46). Incidence of morbidities, including necrotizing enterocolitis, bronchopulmonary dysplasia, retinopathy of prematurity, culture-confirmed sepsis, and feeding intolerance during hospitalization between nHMF and cHMF, were similar (all P-values > 0.05). The time to achieve full enteral feeding [13.5 (10, 21) days] in the nHMF group was significantly shorter than that in the cHMF group [17 (12, 23) days, HR = 0.67, 95%CI: 0.49, 0.92; P = 0.01]. Compared with cHMF group, the decrease of blood urea nitrogen level over time in nHMF group was smaller (β = 0.6, 95%CI:0.1, 1.0; P = 0.01). Conclusions The new HMF can promote growth of preterm infants effectively without increasing the incidence of major morbidity and feeding intolerance. It can be used feasible in Chinese VPT/VLBW infants. Trial registration This study was registered on ClinicalTrials.gov (NCT04283799).

Hypoxia has become a common phenomenon in aquatic environments. Golden pompano (Trachinotus blochii) are sensitive to fluctuations in dissolved oxygen concentration and are seriously affected by hypoxic stress. When facing hypoxia in aquaculture areas, it may be effective to alleviate the adverse effects of low oxygen by increasing dissolved oxygen through physical and chemical means. However, it is not known whether different reoxygenation rates have different physiological consequences. In this study, we utilized RNA-seq and miRNA-seq to investigate the effects of various hypoxia and reoxygenation treatments: normoxia, hypoxia, rapid reoxygenation (RRG; dissolved oxygen [DO] recovery within 10 mins), and gradual reoxygenation (GRG; DO recovery within 3 h). Under hypoxic conditions, the miR-130b-5p∼IDH3 pair was involved in the regulation of the TCA cycle and activation of HIF-1α expression in response to insufficient oxygen levels. Additionally, in RRG, under the regulation of the miR-132–5p∼PGAM, miR-8485∼LIPA, and miR-212–5p∼GAPDHS pairs, the energy supply came to increase relative to hypoxia. In GRG, the miR-130b-5p∼IDH3 pair regulated metabolism, which returned to the normal level. These findings provide new data for clarifying the metabolic regulatory pathways of golden pompano during hypoxia and reoxygenation processes.

Although desert ecosystems are commonly considered to have low carbon storage owing to their sparse vegetation and limited carbon sequestration capacity, they comprise 13.5% of China's terrestrial ecosystems and cover approximately 35% of the Earth's land surface, so they still possess significant carbon storage. The carbon storage of desert ecosystems in China was estimated using MODIS-NDVI data in combination with ground survey, soil census, and literature statistical data. The results indicated that the carbon storage of desert ecosystems in China was 7.063 Pg in 2020. One-meter soil carbon storage accounted for the largest proportion (89.514%), approximately 6.322 Pg, followed by vegetation carbon at 0.741 Pg, and biological soil crust carbon at 0.002 Pg. The carbon density of desert ecosystems was 33.895 Mg.ha−1, with soil carbon density, vegetation carbon density, and biological soil crust carbon density at 30.330, 3.554, and 0.011 Mg.ha−1, respectively. This research provides important evidence for the correct understanding of the carbon storage of desert ecosystems in China.

Abstract Background University students’ academic engagement has a significant impact on their academic performance and career development. Methods In order to explore the influential mechanisms of social support on university students’ academic engagement and the mediating role of academic motivation and life satisfaction, this study used the Adolescent Social Support Scale, University Students’ Academic Engagement Scale Questionnaire, Adolescent Student Life Satisfaction Scale and University Students’ Academic Motivation Questionnaire, to conduct a questionnaire survey and empirical analysis on 2106 Chinese university students. Results (1) social support significantly and positively predicts academic engagement; (2) social support influences academic engagement through the mediating effect of life satisfaction; (3) social support influences academic engagement through the mediating effect of academic motivation; (4) life satisfaction and academic motivation play a chain mediating role in the effect of social support on academic engagement. Conclusions This study contributes to understanding the underlying mechanisms of the relationship between social support and academic engagement, which in turn provides insights for universities and the departments concerned to make measures to improve the level of university students’ academic engagement.

Abstract Background Disrupted sleep is believed to contribute to short- and long-term neurodevelopmental problems in very preterm infants (VPIs). This study presents a protocol for an evaluator-blinded, randomized crossover trial. It aims to assess the sleep efficiency of hospitalized VPIs by providing multisensory stimulation bundles. Furthermore, it aims to observe the intervention impacts on sleep during hospitalization of the VPIs and their sleep and neurodevelopmental outcomes during the first year of post-discharge follow-up. Methods The study will be conducted in the neonatology department of a tertiary pediatric teaching hospital. All the eligible VPIs will undergo two types of care in random order: “standard care” (2 weeks) and “standard care plus multisensory stimulation bundles,” each lasting 2 weeks. A generated list of random numbers will be used for case sequence allocation. Sleep outcomes will be evaluated using the Actiwatch-2 Actigraph. Moreover, the amplitude-integrated electroencephalography and the Griffiths Mental Development Scales will be used to measure the neurodevelopmental outcomes during hospitalization and in the first year of follow-up of the VPIs. Discussion The intervention protocol of this study differs from that of other traditional interventions by producing precise and consistent supportive stimulations, similar to maternal tactile, auditory, posture, and visual effects for hospitalized VPIs. This protocol could be an effective measure to facilitate sleep and early neurodevelopment of VPIs. The expected outcomes will help confirm the implementation and generalization of the multisensory stimulation bundles’ care protocol in neonatology departments. We expect that the study will positively impact hospitalized VPIs, especially in their sleep and early neurodevelopmental outcomes. It will also provide a new perspective regarding parent and infant interaction strategies, particularly for newborn intensive care units that limit visits because of the global spread of COVID-19. Trial registration Chinese Clinical Trial Registry ChiCTR 2200059099. Registered on 25 April 2022, https://www.chictr.org.cn/showproj.html?proj=166980 ; the Hospital Research Ethics Committee (approval number: SCMCIRB-K2021086-1, Version 01), approved on 21 January 2022.

Privacy by design (PbD) has attracted considerable attention from researchers and information security experts due to its enormous potential for protecting private information and improving the privacy and security quality of information technology products. The adoption of PbD among information engineers is currently limited owing to its innovativeness and the distinctive traits of the information technology industry. Utilising the Technology Acceptance Model as a framework, this study innovatively explores the pivotal factors and mechanisms that influence information engineers’ decision-making in the adoption of PbD from the viewpoint of the perceived work risk. In this empirical research, professional information engineers were invited to complete a questionnaire survey. After analysing the data using partial least squares structural equation modelling, the results reveal that information engineers’ perceived work risk in PbD (PWRP) negatively affects their perceptions of the usefulness and ease of use of PbD. This negative perception subsequently reduces their intention to implement PbD (INTP) and adversely impacts their attitudes towards implementing PbD (ATTP). Furthermore, the study findings reveal that a positive ATTP among engineers boosts their INTP and positively influences their behaviours regarding information security. This study provides an in-depth examination of these findings and lays a solid theoretical groundwork for the further promotion and implementation of PbD in information technology enterprises. Moreover, the findings offer invaluable support for management decisions in both information technology companies and information security regulatory authorities, significantly contributing to the expansion and deepening of research in the field of PbD.

We deal with various strains of Lactobacillus that can maintain the intestinal microbiome of rats treated with cyclophosphamide, an anticancer agent (chemotherapy). We use MiSeq and various types of statistical tests to prove that cyclophosphamide in rats alters the intestinal microbiome, favoring the growth of various fungi that are extremely harmful to intestinal metabolism. On the contrary, when Lactobacillus 3L is administered together with cyclophosphamide, we prove that the microbiome is preserved by having a much better intestinal metabolism.

Abstract Introduction The purpose of this systematic review was to research the difference between root-filled teeth (RFT) and vital pulp teeth (VPT) in orthodontically induced external apical root resorption (EARR) and to offer suggestions for clinicians on therapeutic sequence and timing when considering combined treatment of endodontic and orthodontic. Materials and methods An electronic search of published studies was conducted before November 2022 in PubMed, Web of Science and other databases. Eligibility criteria were based on the Population, Intervention, Comparison, Outcome, and Study design (PICOS) framework. RevMan 5.3 software was used for statistical analysis. Single-factor meta-regression analysis was used to explore the sources of literature heterogeneity, and a random effects model was used for analysis. Results This meta-analysis comprised 8 studies with 10 sets of data. As there was significant heterogeneity among the studies, we employed a random effects model. The funnel plot of the random effects model exhibited a symmetrical distribution, indicating no publication bias among the included studies. The EARR rate of RFT was significantly lower than that of VPT. Conclusions In the context of concurrent endodontic and orthodontic treatment, priority should be given to endodontic therapy, as it serves as the foundation for subsequent orthodontic procedures. The optimal timing for orthodontic tooth movement post-root canal therapy is contingent upon factors such as the extent of periapical lesion resolution and the degree of dental trauma sustained. A comprehensive clinical assessment is essential in guiding the selection of the most suitable approach for achieving optimal treatment outcomes.

Abstract Background Maternal systemic lupus erythematosus (SLE) is at greater risk of pregnancy complications and is associated with increased risk of preterm delivery. However hardly any study has looked at the influence of SLE on the outcomes of preterm infants. This study aimed to explore the influence of SLE on the outcomes of preterm infants. Methods In this retrospective cohort study, preterm infants born to mothers with SLE from Shanghai Children’s Medical Center during 2012 to 2021 were enrolled. Infants were excluded if they were died during hospitalization or has major congenital anomalies and neonatal lupus. Exposure was defined as mother diagnosed SLE before or during pregnancy. Maternal SLE group was matched with Non-SLE group by gestational age, birth weight and gender. Clinical data has been extracted from patients’ records and registered. Major morbidities of premature and biochemical parameters in the two groups were compared using multiple logistic regression. Results One hundred preterm infants born to 95 mothers with SLE were finally enrolled. The mean (standard deviation) of gestational age and birth weight were 33.09 (7.28) weeks and 1768.50 (423.56) g respectively. There was no significant difference in major morbidities between SLE group and non-SLE group. Compared with non-SLE group, SLE off-spring had significantly lower leukocytes, neutrophiles after birth, neutrophils and platlet in one week (mean difference: -2.825, -2.001, -0.842, -45.469, respectively). Among SLE group, lower birth weight and smaller gestational age were observed in SLE mothers with disease active during pregnancy, kidney involved, blood system involved and not taking Aspirin during pregnancy. In the multivariable logistic regression analysis, exposure to aspirin during pregnancy reduced the risk of very preterm birth and increased the incidence of survive without major morbidities among preterm infants born to SLE mothers. Conclusion Born to mothers with SLE may not increase the risk of major premature morbidities, but the hematologic profile of SLE preterm infants may be different from preterm infants born to women without SLE. The outcome of SLE preterm infants is associated with maternal SLE status and may benefit from maternal aspirin administration.

Abstract Xenogenic organ transplantation has been considered the most promising strategy in providing possible substitutes with the physiological function of the failing organs as well as solving the problem of insufficient donor sources. However, the xenograft, suffered from immune rejection and ischemia-reperfusion injury (IRI), causes massive reactive oxygen species (ROS) expression and the subsequent cell apoptosis, leading to the xenograft failure. Our previous study found a positive role of PPAR-γ in anti-inflammation through its immunomodulation effects, which inspires us to apply PPAR-γ agonist rosiglitazone (RSG) to address survival issue of xenograft with the potential to eliminate the excessive ROS. In this study, xenogenic bioroot was constructed by wrapping the dental follicle cells (DFC) with porcine extracellular matrix (pECM). The hydrogen peroxide (H2O2)-induced DFC was pretreated with RSG to observe its protection on the damaged biological function. Immunoflourescence staining and transmission electron microscope were used to detect the intracellular ROS level. SD rat orthotopic transplantation model and superoxide dismutase 1 (SOD1) knockout mice subcutaneous transplantation model were applied to explore the regenerative outcome of the xenograft. It showed that RSG pretreatment significantly reduced the adverse effects of H2O2 on DFC with decreased intracellular ROS expression and alleviated mitochondrial damage. In vivo results confirmed RSG administration substantially enhanced the host’s antioxidant capacity with reduced osteoclasts formation and increased periodontal ligament-like tissue regeneration efficiency, maximumly maintaining the xenograft function. We considered that RSG preconditioning could preserve the biological properties of the transplanted stem cells under oxidative stress (OS) microenvironment and promote organ regeneration by attenuating the inflammatory reaction and OS injury.

This study aims to investigate the relationship between the grades of Tuo tea and the quality of compounds. A combination of artificial sensory evaluation, intelligent sensory technologies (electronic nose and electronic tongue), gas chromatography–mass spectrometry (GC-MS), high-performance liquid chromatography (HPLC), chemical–physical analysis, and multivariate statistical analysis were employed to examine the differences among three grades of Tuo tea (SG, 1G, and 2G). The results of artificial sensory evaluation, electronic tongue, and electronic nose revealed that the aroma and taste of different grades of Tuo tea varied greatly. A total of 112 volatile compounds and 44 non-volatile compounds were identified. In order to elucidate the key components that cause differences in the quality of Tuo tea, 2 partial least squares discriminant analysis (PLS-DA) models with excellent parameters (volatile, R2Y = 0.999 and Q2 = 0.996; non-volatile, R2Y = 0.992 and Q2 = 0.972) were established. A total of 80 key differential volatile compounds were identified with the double selection criterion of variable importance in projection (VIP) greater than 1 and p < 0.05. Among these, 43 compounds with OAV > 1 were further identified as the odor-active compounds in all three grades of Tuo. Moreover, 22 key non-volatile compounds that contribute to the quality differences have been screened out. This investigation implied that the volatile and non-volatile compounds of Tuo tea could serve as indicators of its quality. The results provided a new approach to distinguish the grades of Tuo tea.

The fluctuations of dissolved oxygen (DO) often lead to hypoxia in aquaculture, which has a huge adverse impact on fish. This study mainly investigated the effects of long-term hypoxia on oxidative stress, immune response, and cell apoptosis in the liver of golden pompano (Trachinotus blochii), which is not tolerant to hypoxia. So we conducted a 14 day low oxygen stress experiment on the golden pompano with a DO of 3.0 ± 0.2 mg/L, then restore the DO to normal levels and continue the 14 day reoxygenation experiment. Results showed that hypoxia and reoxygenation led to significant changes in liver structure. During hypoxia and reoxygenation, the expression of oxidative stress related genes (SOD1, SOD2, GSH-Px, and CAT) and levels of antioxidant enzymes (CAT and MDA) in the liver were increased. Liver lysozyme activity and the relative expression of the pro-inflammatory factors interleukin (IL)-1β were significantly increased, but the expression of IL-34 was down-regulated during hypoxia. The expression of IL-12β was significantly increased during reoxygenation. The expression of anti-inflammatory factor IL-11 was decreased duringreoxygenation. The expression of toll like receptors (TLRs) -7, -8, and -9 increases after hypoxia and decreases after reoxygenation, indicating that both hypoxia and reoxygenation affect the immune response. In addition, during hypoxia and reoxygenation, TUNEL-positive signals increased, the bcl2/bax ratio decreased, the expression levels of caspases-3 and -8 were significantly up-regulated during hypoxia, and expression levels of caspases-9 was up-regulated during reoxygenation. In summary, hypoxia and reoxygenation can cause oxidative stress, induce inflammatory reactions, inhibit immune processes, activate apoptosis, and lead to liver damage of the golden pompano, which may be irreversible.

BackgroundSecond primary colorectal cancer (CRC) is attributed to a crucial component of the CRC population. Still, its treatments remain unclear due to the troublesome conditions originating from multiple primary cancers and the lack of quality evidence. This study aimed to determine that which type of surgical resection is the eligible treatment for second primary CRC among patients with a prior cancer history.MethodsThis cohort study retrospectively collected patients with second primary stage 0-III CRC in the Surveillance, Epidemiology, and End Results database from 2000 to 2017. Prevalence of surgical resection in second primary CRC, overall survival (OS) and disease-specific survival (DSS) of patients who received different surgical interventions were estimated.ResultsA total of 38,669 patients with second primary CRC were identified. Most of the patients (93.2%) underwent surgical resection as initial treatment. Approximately 39.2% of the second primary CRCs (N = 15,139) were removed with segmental resection, while 54.0% (N = 20,884) were removed through radical colectomy/proctectomy. Surgical resection was associated with a significantly favorable OS and DSS compared to those not receiving any surgical operations for second primary CRC [OS: adjusted Hazard ratios (adjusted HR): 0.35; 95% CI: 0.34–0.37, p

Abstract Background Colorectal cancer (CRC) is a deadly and commonly diagnosed cancer. Cell‐free circulating tumor DNAs (ctDNA) have been used in the diagnosis and treatment of CRC, but there are open questions about the relationship between ctDNAs and CRC. Although mutations of genes detected by ctDNA in CRC have been studied, the quantitative relationship between ctDNA mutations and ctDNA concentration has not been addressed. Aims We hypothesized that there was an association between mutations of genes identified in ctDNAs and ctDNA concentration. His study examined this association in a population of CRC patients. Methods In 85 CRC patients, we sampled 282 mutations in 36 genes and conducted an association study based on a Random forest model between mutations and ctDNA concentrations in all patients. Results This association study showed that mutations on five genes, ALK, PMS2, KDR, MAP2K1, and MSH2, were associated with the ctDNA concentrations in CRC patients’ blood samples. Because ctDNA mutations correlate with ctDNA level, we can infer the tumor burden or tumor size from ctDNA mutations, as well as the survival time for prognosis. Conclusion Our findings shed light on the associations between mutations of genes identified in ctDNAs and ctDNA concentration in the blood of CRC patients. This discovery provides information regarding the tumor burden or tumor size based on ctDNA mutations.

Abstract Background To explore the application value of free omental wrapping and modified pancreaticojejunostomy in pancreaticoduodenectomy (PD). Methods The clinical data of 175 patients who underwent pancreaticoduodenectomy from January 2015 to December 2020 were retrospectively analysed. In total, 86 cases were divided into Group A (omental wrapping and modified pancreaticojejunostomy) and 89 cases were divided into Group B (control group). The incidences of postoperative pancreatic fistula and other complications were compared between the two groups, and univariate and multivariate logistic regression analyses were used to determine the potential risk factors for postoperative pancreatic fistula. Risk factors associated with postoperative overall survival were identified using Cox regression. Results The incidences of grade B/C pancreatic fistula, bile leakage, delayed bleeding, and reoperation in Group A were lower than those in Group B, and the differences were statistically significant (P

ObjectiveTo analyze the application value of two postural fixation techniques.(styrofoam combined with head mask and fixed headrest combined with head mask) in intracranial tumor radiotherapy via cone beam computed tomography (CBCT).MethodsThis study included 104 patients with intracranial tumors undergoing radiotherapy. The patients were divided into two groups: Group A (54 cases with styrofoam fixation) and Group B (50 cases with fixed headrest fixation). The positional deviation in 3D space between the two groups was compared using CBCT. The set-up errors were expressed as median (25th percentile, 75th percentile)or M(p25, p75) since the set-up errors in all directions were not normally distributed,The Mann-Whitney U test was performed.ResultsThe age and gender of patients in the two groups were not significantly different. The set-up errors of A in lateral (X), longitudinal (Y), vertical (Z), and yaw(Rtn) axes were 1.0 (0,1) mm, 1.0 (0,1) mm, 1.0 (0,2) mm, and 0.4 (0.1, 0.8) degrees, respectively while the set-up errors of B were 1.0 (0,1) mm, 1.0 (1,2) mm, 1.0 (0,2) mm, and 0.5 (0.15,0.9) degrees, respectively. Moreover, patients in the styrofoam group had significantly smaller set-up errors in the Y-axis than patients in the headrest group (p=0.001). However, set-up errors in the X, Z, and Rtn axes were not significantly different between the two groups. The expansion boundaries of the target area in the X, Y, and Z directions were 1.77 mm, 2.45 mm, and 2.47 mm, respectively. The outer expansion boundaries of the headrest group were 2.03 mm, 3.88 mm, and 2.57 mm in X, Y, and Z directions, respectively. The set-up times of groups A and B were (32.71 ± 5.21) seconds and (46.57 ± 6.68) seconds, respectively (p=0.014). Patients in group A had significantly better comfort satisfaction than patients in group B (p=0.001).ConclusionStyrofoam plus head thermoplastic mask body fixation technique has a higher positional accuracy in intracranial tumor radiotherapy than headrest plus head thermoplastic mask fixation. Besides, styrofoam plus head thermoplastic mask body fixation technique is associated with improved positioning efficiency, and better comfort than headrest plus head thermoplastic mask fixation, and thus can be effectively applied for intracranial tumor radiotherapy positioning.

Globally, microplastics (MPs) are highly prevalent, especially in coastal areas. Unfortunately, golden pompano as a major marine fish in China is typically raised in floating marine cages near coasts, facing these MPs sources. However, toxicological studies on Golden Pompano which farm in coastal areas and face actual microplastic exposure are rare. Therefore, golden pompano were exposed to 10.0 μg/L, 100.0 μg/L, and 1000.0 μg/L polystyrene MPs (PS-MPs) for 14 days to study the potential impact of the microplastics on the Golden Pompano. Fish show slowed growth after 14 days of exposure. Histopathology shows irregular shaped nuclei and nuclear and cytoplasmic vacuolation traits in liver. Oxidative stress-related enzyme activity and gene expression data show that oxidative damage occurs in the high-concentrations (100.0 μg/L and 1000.0 μg/L) of PS-MPs exposures. Up-regulation of Grp78, Xbp-1, Eif-2α and chop gene expression indicates the occurrence of endoplasmic reticulum stress, and the western blot results also confirmed this. Severe oxidative stress also caused ERS, which ultimately increased BAX/Bcl-2 ratios and induces apoptosis. Furthermore, up-regulated anaerobic respiration, altered lipid metabolism, and immune disturbance were exhibited during PS-MPs stress. Therefore, oxidative stress appeared to be the main toxicity issue caused by MPs, while ERS-mediated apoptosis, metabolic alterations, and immune responses were induced by this stress. Notably, endoplasmic reticulum stress and apoptosis are a self-protective mechanism, which may be an intermediate link in the toxicity of microplastics. This study highlights the role of endoplasmic reticulum stress in MPs toxicology and assesses the adverse effects of microplastics on Golden Pompano.

The CCD gene family plays a crucial role in the cleavage of carotenoids, converting them into apocarotenoids. This process not only impacts the physiology and development of plants but also enhances their tolerance toward different stresses. However, the character of the PmCCD gene family and its role in ornamental woody Prunus mume remain unclear. Here, ten non-redundant PmCCD genes were identified from the P. mume genome, and their physicochemical characteristics were predicted. According to the phylogenetic tree, PmCCD proteins were classified into six subfamilies: CCD1, CCD4, CCD7, CCD8, NCED and CCD-like. The same subfamily possessed similar gene structural patterns and numbers of conserved motifs. Ten PmCCD genes were concentrated on three chromosomes. PmCCD genes exhibited interspecific collinearity with P. armeniaca and P. persica. Additionally, PmCCD genes had obvious specificity in different tissues and varieties. Compared with white-flowered ‘ZLE’, PmCCD1 and PmCCD4 genes were low-expressed in ‘HJH’ with yellow petals, which suggested PmCCD1 and PmCCD4 might be related to the formation of yellow flowers in P. mume. Nine PmCCD genes could respond to NaCl or PEG treatments. These genes might play a crucial role in salt and drought resistance in P. mume. Moreover, PmVAR3 and PmSAT3/5 interacted with PmCCD4 protein in yeast and tobacco leaf cells. This study laid a foundation for exploring the role of the PmCCD gene family in flower coloration and stress response in P. mume.

Prunus mume is a famous ornamental woody tree with colorful flowers. P. mume with yellow flowers is one of the most precious varieties. Regretfully, metabolites and regulatory mechanisms of yellow flowers in P. mume are still unclear. This hinders innovation of flower color breeding in P. mume. To elucidate the metabolic components and molecular mechanisms of yellow flowers, we analyzed transcriptome and metabolome between ‘HJH’ with yellow flowers and ‘ZLE’ with white flowers. Comparing the metabolome of the two varieties, we determined that carotenoids made contributions to the yellow flowers rather than flavonoids. Lutein was the key differential metabolite to cause yellow coloration of ‘HJH’. Transcriptome analysis revealed significant differences in the expression of carotenoid cleavage dioxygenase (CCD) between the two varieties. Specifically, the expression level of PmCCD4 was higher in ‘ZLE’ than that in ‘HJH’. Moreover, we identified six major transcription factors that probably regulated PmCCD4 to affect lutein accumulation. We speculated that carotenoid cleavage genes might be closely related to the yellow flower phenotype in P. mume. Further, the coding sequence of PmCCD4 has been cloned from the ‘HJH’ petals, and bioinformatics analysis revealed that PmCCD4 possessed conserved histidine residues, ensuring its enzymatic activity. PmCCD4 was closely related to PpCCD4, with a homology of 98.16%. Instantaneous transformation analysis in petal protoplasts of P. mume revealed PmCCD4 localization in the plastid. The overexpression of PmCCD4 significantly reduced the carotenoid content in tobacco plants, especially the lutein content, indicating that lutein might be the primary substrate for PmCCD4. We speculated that PmCCD4 might be involved in the cleavage of lutein in plastids, thereby affecting the formation of yellow flowers in P. mume. This work could establish a material and molecular basis of molecular breeding in P. mume for improving the flower color.

In this article, we expound the important role of an emergency rescue system in handling public health emergencies, summarize the characteristics of China’s fight against the COVID-19 epidemic from the perspective of emergency rescue capacity building, and reflect on the experiences and lessons regarding emergency rescue to combat the epidemic. This study is expected to help improve relevant national policies and systems, strengthen the health protection net for the people, and maintain a sound environment for national security development in China. Moreover, we summarize the main contents and characteristics of the three stages for developing China’s emergency rescue system and analyze the existing problems from three aspects: mechanism, resources, and overall level. Furthermore, we propose several specific countermeasures and suggestions for the construction of the emergency rescue system for public health emergencies in China from the aspects of handling modes, scientific layout and function promotion, talent team construction, emergency material support, grass-roots capacity building, multi-disciplinary integration, scientific research–disease control–clinical treatment coordination, wartime mobilization mechanism, international cooperation, and action outline formulation.

IntroductionSoil testing formula fertilization using organic fertilizer (STFFOF)could increase grain yields and protect the ecological environment but the potential risks of STFFOF remains unclear.MethodsIn order to assess the risk on rice stem lodging, a STFFOF field experiment is conducted continuously for 11 years.ResultsAfter 11 years of continuous STFFOF treatment, the stem lodging rate of rice substantially increases by 81.1%*, which completely overweigh its increase in yield. Further research found that STFFOF greatly decreases the concentration of Ca, SiO2, K, Mg, and non-structural carbohydrates in basal internodes, dramatically increases that of N, P, and weight per ear, but slightly affects the structural carbohydrates. The strong correlations imply the increasement in weight per ear, N, and P concentrations, and the significant decrease in starch in the basal internodes might directly increase the brittleness of stem internodes and further cause severe stem lodging and yield loss of rice.DiscussionResults suggest that the potential risks of rice production including stem lodging must be considered when adopting the excessive exploration mode of productivity technology of paddy fields.

Golden pompano (Trachinotus blochii) is becoming increasingly popular and produces high yields, but the growth differences between males and females are a concern. In this study, the differences between the growth of males and females were compared, and the transcriptome analysis of muscle tissues was performed. A significant difference between the growth of males and females was observed; females were found to be 17% larger than males after reaching 7 months of age. Gonadal histological analysis revealed that the ovaries were arrested in 7- to 9-month-old golden pompano, whereas the testes continued to develop. The AMPK and adipocytokine signaling pathways were also found to be involved in the regulation of muscle growth and metabolism. After reaching 7 months of age, the expression levels of glut1, glut4, ldh, gys, acsl and cpt2 in the muscle of females were lower than those in males, but the hk gene, which is involved in glycolysis, was found to remain highly expressed in females. Additionally, in females, the synthesis of arginine and ornithine and the production of carnosine were found to be inhibited, but the breakdown of glutamine was found to be enhanced and OXPHOS ability was found to be stronger in females after reaching 7 months of age. These results support a certain negative correlation between gonadal development and muscle metabolism depending on differences in energy distribution. Clearly, the faster growth in females after reaching 7 months of age was found to be associated with the more active metabolism of glucose, and amino acids, as well as stronger oxidative phosphorylation levels.

Abstract Background Primary small cell carcinoma of the pancreas (SCCP) is a rare malignant neuroendocrine carcinoma (NEC). Typically, it presents with lymphovascular invasion as well as metastasis at the time of diagnosis which portends a dismal prognosis. Treatment is typically based on therapy used for other aggressive NECs such as small cell lung cancer. Although multimodal surgery, radiation and chemotherapy may improve prognosis, the outcome generally remains poor. Case presentation Here we present a primary SCCP managed with neoadjuvant multi-agent chemotherapy combined with radiotherapy and surgery Conclusions Multi-disciplinary therapy resulted in an ongoing 28 + month radiographic complete response and overall survival.