Blood urea nitrogen to albumin ratio is a novel predictor of fatal outcome for patients with severe fever with thrombocytopenia syndrome.

Severe fever with thrombocytopenia syndrome (SFTS) is associated with a high death rate and lacks a targeted therapy plan. The ratio of blood urea nitrogen to albumin, known as BAR, is a valuable method for assessing the outlook of various infectious diseases. The objective of this research was to evaluate the effectiveness of BAR in forecasting the outcome of individuals with SFTS. Four hundred and thirty-seven patients with SFTS from two clinical centers were included in this study according to inclusion and exclusion criteria. Clinical characteristics and test parameters of SFTS patients were analyzed between survival and fatal groups. Least absolute shrinkage and selection operator (LASSO) regression and Cox regression suggested that BAR might serve as a standalone prognostic indicator for patients with SFTS in the initial phase (hazard ratio = 18.669, 95% confidence interval [CI]: 8.558-40.725, p < 0.001). And BAR had a better predictive effectiveness in clinical outcomes in patients with SFTS with an AUC of 0.832 (95% CI: 0.788-0.876, p < 0.001), a cutoff value of 0.19, a sensitivity of 0.812, and a specificity of 0.726 compared to C-reactive protein, procalcitonin, and platelet to lymphocyte ratio via receiver operating characteristic curve. KM (Kaplan Meier) curves demonstrated that high level of BAR was associated with poor survival condition in patients with SFTS. Furthermore, the high level of BAR was associated with long hospital stays and test paraments of kidney, liver, and coagulation function in survival patients. So, BAR could be used as a promising early warning biomarker of adverse outcomes in patients with SFTS.

Case Report: Ventricular preexcitation-induced dilated cardiomyopathy improved by the pharmacologic suppression of ventricular preexcitation in three infants, and literature review.

The therapy of ventricular preexcitation-induced dilated cardiomyopathy in very small infants or infants with a high risk of ablation is tough and related articles are rare. Effective pharmacotherapy to suppress ventricular preexcitation is valuable. Aims: To evaluate the effectiveness and safety of pharmacotherapy for cardiac resynchronization in infants with ventricular preexcitation-induced dilated cardiomyopathy. Methods and results: Three infants with ventricular preexcitation-induced dilated cardiomyopathy, due to the disappearance of ventricular preexcitation during the placement of catheter, intermittent WPW pattern, and right mid septal accessory pathway respectively, had received pharmacotherapy for cardiac resynchronization. The initial dosage of oral amiodarone was 5 mg/kg.d and it was followed by the maintenance dosage of 2-2.5 mg/kg.d 4 weeks later. Propafenone (15 mg/kg.d) served as a supplement since amiodarone was not adequate in case 3. The three infants achieved successful pharmacologic suppression of ventricular preexcitation 10, 6.5, and 4.5 weeks after the initiation of amiodarone respectively. They all got normalized contraction of interventricular septum and LVEF as well as reduced LVEDD gradually after the disappearance of ventricular preexcitation. No side effects associated with pharmacotherapy happened during the follow-up. Amiodarone had been withdrawn for 2 years and 5 months in Cases 1 and 2. They both remained free from ventricular preexcitation and retained normal LVEF and LVEDD. Conclusions: Pharmacotherapy for cardiac resynchronization with oral amiodarone or in combination with propafenone for infants with ventricular preexcitation-induced dilated cardiomyopathy is effective and safe. Pharmacotherapy for cardiac resynchronization served as another therapeutic choice besides ablation.

Highly sensitive and accurate detection of cholesterol based on a single red upconversion biosensor.

Cholesterol (CHOL) is an important clinical biochemical indicator that plays an important role in the regulation of the fluidity, permeability, and microstructure of cell membranes. Therefore, it is necessary to accurately monitor CHOL levels in biological samples for the early prevention and diagnosis of various diseases. The single-band red upconversion nanoparticle (UCNP) emits light within the optical transmission window of biological tissues, and can penetrate deeper biological tissues and cause less energy loss due to scattering and thus have higher sensitivity and accuracy. Here, using the nontoxic, sensitive, and photochemically stable 3,3',5,5'-tetramethylbenzidine (TMB) as the quenching agent and single red UCNP as the fluorescent donor, a dual-readout colorimetric and fluorescent sensor was developed to detect CHOL. The detection mechanism and feasibility were discussed in detail, and experimental conditions such as Fe2+ concentration, TMB concentration and reaction time were explored. Under optimal conditions, the limits of CHOL detection by colorimetry and fluorescence were 0.85 µM and 0.63 µM. The sensing system was used to measure CHOL in serum samples and the values obtained by these two modes were close, and the spiked recoveries were 97.2-102.2% and 97.1-103.7%, respectively, which holds great potential in clinical diagnosis and health management.

Discovery of new dibenzodiazepine derivatives as antibacterials against intracellular bacteria.

The emergence and spread of multidrug-resistant bacteria underscore the critical need for novel antibacterial interventions. In our screening of 12 synthesized thienobenzodiazepines, pyridobenzodiazepines, and dibenzodiazepines, we successfully identified a small molecule compound SW33. Notably, SW33 demonstrated potent inhibitory activity against intracellular multidrug-resistant and fluoroquinolone-resistant strains of S. typhimurium in both macrophages and epithelial cells. Furthermore, SW33 was also effective against intramacrophagic Salmonella typhi, Yersinia enterocolitica, and Listeria monocytogenes. These significant findings suggest that SW33 possesses broad-spectrum activity against intracellular bacteria.

Applying the projection pursuit and DPSIR model for evaluation of ecological carrying capacity in Inner Mongolia Autonomous Region, China.

The ecological carrying capacity (ECC) of Inner Mongolia is the foundation of its sustainable development. As a result, a comprehensive investigation of Inner Mongolia's ECC and its influencing factors is critical for promoting regional sustainable development. However, an ECC evaluation index system for the ecological environment and economic development features of Inner Mongolia has not yet been developed. In addition, as ECC attributes rise, traditional methods become ineffective at extracting the structural characteristics of high-dimensional data, leading to an incomplete evaluation. In view of this, based on the driver-pressure-state-impact-response (DPSIR) framework, we developed an ECC evaluation index system that takes into account the ecological environment and economic development features of Inner Mongolia. The projection pursuit model based on real coded accelerating genetic algorithm (RAGA-PP), which can analyze high-dimensional data, was applied to achieve ECC comprehensive assessment in Inner Mongolia. Finally, the analysis of the ECC obstacle factors in the study area was conducted. The findings reveal that (1) from 2000 to 2020, there was an average increase of 28.4% in the ECC for all of Inner Mongolia cities. The spatial divergence feature is obvious, and the northeastern cities' ECC is higher than the southwestern. (2) From 2000 to 2020, the value of the drive, pressure, and state subsystems primarily shows fluctuation. The impact and response subsystems both exhibit an increase, while the response subsystem's characteristic values are lower. (3) The obstacle degree of driving force subsystem is significant and ranges from 17.6 to 33.9% between 2000 and 2020. Main obstacles to ECC are the average annual temperature, the disposable income of farmers and herdsmen, the urban registered unemployment rate, and the seeded area per capita. The findings of the research can provide useful guidance to developing efficient policies that take into account the various ECC in different cities in order to improve ECC performance throughout Inner Mongolia.

Platelet-Based Nanoparticles with Stimuli-Responsive for Anti-Tumor Therapy.

In addition to hemostasis and coagulation, years of studies have proved that platelets are involved in the whole process of tumor progression, including tumor invasion, intravasation, extravasation, and so on. It means that this property of platelets can be used in anti-tumor therapy. However, traditional platelet-based antitumor drugs often cause autologous platelet damage due to lack of targeting, resulting in serious side effects. Therefore, the researchers designed a variety of anti-tumor drug delivery systems based on platelets by targeting platelets or platelet membrane coating. The drug delivery systems have special response modes, which is crucial in the design of nanoparticles. These modes enhance the targeting and improve the anti-tumor effect. Here, we present a review of recent discoveries in the field of the crosstalk between platelets and tumors and the progress of platelet-based anti-tumor nanoparticles.

LINC01268 promotes epithelial-mesenchymal transition, invasion and metastasis of gastric cancer via the PI3K/Akt signaling pathway and targeting MARCKS.

BACKGROUND: Long non-coding RNAs (lncRNAs) with differential expression characteristics have been found to be closely related to the tumorigenesis and development of gastric cancer (GC), but their specific mechanisms and roles still need to be further elucidated. AIM: To investigate the expression of LINC01268 in GC and its mechanism of affecting GC progression. METHODS: Real-time quantitative polymerase chain reaction was used to detect the expression of LINC01268 in GC tissues, cell lines and plasma. The Kaplan-Meier method was used to evaluate the value of LINC01268 in the prognostication of GC patients. An receiver operating characteristic curve was constructed to evaluate the value of LINC01268 in the diagnosis of GC. Transwell migration and invasion assays and wound healing assays were used to confirm the effect of LINC01268 on the invasion and migration of GC cells. The regulatory relationship between LINC01268 and myristoylated alanine rich protein kinase C substrate (MARCKS), the PI3K/Akt signaling pathway, and the epithelial-mesenchymal transition (EMT) process in GC was demonstrated by western blot analysis. RESULTS: The expression of LINC01268 was increased in GC tissues and cell lines. The expression level of LINC01268 was significantly correlated with lymph node metastasis, TNM stage, and tumor differentiation in patients with GC. Over-expression of LINC01268 indicated a poor prognosis for patients with GC, and it had a certain auxiliary diagnostic value for GC. In vitro functional experiments proved that the abnormal expression of LINC01268 further activated the PI3K/Akt signaling pathway and promoted EMT by targeting and regulating MARCKS and ultimately promoted the invasion and metastasis of GC. CONCLUSION: This study elucidates that LINC01268 in GC may be an oncogene that further activates the PI3K/Akt signaling pathway and EMT by targeting and regulating MARCKS, and ultimately promotes the invasion and metastasis of GC. LINC01268 may be a potential effective target for the treatment of GC.

Spatiotemporal change and driving factors of ecological status in Inner Mongolia based on the modified remote sensing ecological index.

Remote sensingmonitoring of regional ecological quality has advanced significantly with the rapid developments of remote sensing technology. At present, remote sensing ecological index (RSEI) has been widely used in ecological status monitoring. However, RSEI was proposed for urban environments, and the rationality and accuracy of its applicability to desert-dominated arid region ecosystems need to be demonstrated. Therefore, in this study, we incorporated desertification monitoring index (DMI) and salinity monitoring index (SMI) to RSEI and developed the modified remote sensing ecological index (MRSEI) for arid regions. Moreover, we analyzed the stability of MRSEI in ecological status monitoring for arid regions. The MRSEI was then used to evaluate the ecological quality of Inner Mongolia from 2000 to 2020 and exploring its causes. The results show that (1) Although the evaluation results of RSEI and MRSEI are more consistent in areas with high ecological status grades, the MRSEI results are more cautious and reliable in extreme conditions (e.g., desertification, salinization) than the RSEI. (2) Approximately 87.66% of ecological quality have improved or remain stable from 2000 to 2020, but the remaining areas (accounting for 12.34% of the whole area) are still under degraded conditions. This demonstrates that although local governments have made some progress in ecological conservation, the areas that are fluctuating or degraded still require protection or management. (3) In Inner Mongolia, the ecological quality which drove by precipitation (P) & temperature (T) accounting for 26.67% of the study area, population density (D) and GDP per capita (G) affected 13.23% of regional ecological quality. Overall, this research is crucial for evaluating spatial and temporal changes in arid region ecology and establishing conservation strategies.

Repurposing the tyrosine kinase inhibitor nilotinib for use against intracellular multidrug-resistant Salmonella Typhimurium.

BACKGROUND/PURPOSE: The increasing incidence of infections caused by multidrug-resistant Salmonella enterica has become a serious threat to global public health. Here, we found that the tyrosine kinase inhibitor nilotinib exhibits antibacterial activity against intracellular S. enterica serovar Typhimurium in RAW264.7 macrophages. Thus, we aimed to pharmacologically exploit the anti-intracellular Salmonella activity of nilotinib and to elucidate its mechanism of action. METHODS: The antibacterial activity of the compounds was assessed by high-content analysis (HCA) and intracellular CFU, minimum inhibitory concentration (MIC), and bacterial growth assays. The cytotoxicity of the compounds was evaluated by HCA and a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) cell viability assays. The levels of cellular AMPK, phospho-AMPK, Atg7 and ß-actin were determined by immunoblotting. RESULTS: The screen identified two small molecule compounds (SCT1101 and SCT1104) with potent activity against intracellular S. Typhimurium. Moreover, SCT1101 and SCT1104 enhanced the efficacy of ciprofloxacin and cefixime against intracellular S. Typhimurium. However, only SCT1101 exhibited activity against intracellular MDR and fluoroquinolone-resistant S. Typhimurium isolates. Subsequent mechanistic studies showed that neither of these nilotinib derivatives increased the phospho-AMPK level in RAW264.7 cells. Neither the AMPK inhibitor compound C nor SBI-0206965 reversed the inhibitory effects of SCT1101 and SCT1104 on intracellular Salmonella. Furthermore, neither blockade of autophagy by 3-MA nor shRNA-mediated knockdown of Atg7 protein expression in RAW264.7 cells affected the antibacterial activity of SCT1101 and SCT1104. CONCLUSION: The structure of nilotinib could be used to develop novel therapeutics for controlling MDR S. Typhimurium infections.

Analysis of land subsidence caused by hydrodynamic force in Loess Hilly and gully region based on SBAS-InSAR.

After large-scale land consolidation in hilly loess region of the Loess Plateau in China, land subsidence has a wide affecting area and considerable difficulty of prevention. Hence, large-scale, stabilized, and continuous deformation monitoring is urgently needed for slopes. In this study, land consolidation zone in the loess platform area of Weinan, China, was selected as the object, and the 30-scene Sentinel-1A data in Jan, 2018 to Dec, 2019 were analyzed. The mean annual velocity of ground deformation was from -6.19 mm∙a-1 to 3.86 mm∙a-1, and Accumulated deformation velocity was within -8.49 mm∙a-1 to 7.24 mm∙a-1. Accumulated deformation of land consolidation changed with the seasons changing. The interrelationship between the spatiotemporal variations in ground subsidence and the precipitation, ground water, loess engineering properties was also discussed. Accumulated deformation of land consolidation changed with the seasons changing. The precipitation accelerated the subsidence by unexpected strong precipitation reflects that the infiltration of rainwater can lead to compacted loess deformation which caused by moistening effect. Under varying ground water environment, external loads may lead to soil collapse, resulting in non-uniform land subsidence. Co-compression deformation of original loess and compacted loess is main influencing factors of subsidence. These findings have important implications and significant positive effects on the prevention of potential hazard such as subsidence and side slope slip.

Discovery of antipsychotic loxapine derivatives against intracellular multidrug-resistant bacteria.

The emergence and spread of multidrug-resistant bacteria highlight the need for new antibacterial interventions. A screening of 24 newly synthesized dibenzoxazepines identified a small molecule compound, SW14, with potent inhibitory activity against intracellular multidrug-resistant and fluoroquinolone-resistant strains of S. typhimurium in macrophages and epithelial cells. Moreover, intra-macrophagic Salmonella typhi, Yersinia enterocolitica, and Listeria monocytogenes and methicillin-resistant Staphylococcus aureus are also susceptible to SW14. Overall, our findings suggest that SW14 has a broad-spectrum activity against intracellular bacteria.

CEP63 upregulates YAP1 to promote colorectal cancer progression through stabilizing RNA binding protein FXR1.

Abnormal regulation of centrosome components can induce chromosome instability and tumorigenesis. Centrosomal protein 63 (CEP63) is a vital member for assembling centrosome. Yet, the involvement of CEP63 in cancer pathogenesis remains unclear. Here we identify CEP63 as an important mediator for RNA-binding proteins (RBPs) to facilitate regulation on their RNA targets in colorectal cancer (CRC). We demonstrate that CEP63 protein is upregulated in a large cohort of colorectal cancer tissues and predicts poor prognosis, and USP36 is identified for stabilizing CEP63 by enhancing its K48-dependent deubiquitination. CEP63 overexpression promotes the proliferation and tumor growth of CRC cells in vitro and in vivo. Furthermore, we find that CEP63 can promote cancer stem-like cell properties by enhancing YAP1 expression through binding with and inhibiting the K63-ubiquitylation degradation of RBP FXR1 in CRC cells. Importantly, we further verify that the KH domain of FXR1 is necessary for the interaction between CEP63 and FXR1. Moreover, microtube motor proteins can form a complex with CEP63 and FXR1 to mediate the regulation of FXR1 on RNA targets. Additionally, we also confirm that CEP63 can bind and regulate multiple RBPs. In conclusion, our findings unveil an unrecognized CEP63/RBPs/RNA axis that CEP63 may perform as an adapter facilitating the formation of RBPs complex to regulate RNA progression and discover the role of CEP63 involved in signal transduction and RNA regulation, providing potential therapeutic target for CRC patients.

Osteosarcopenic obesity and its components-osteoporosis, sarcopenia, and obesity-are associated with blood cell count-derived inflammation indices in older Chinese people.

BACKGROUND: The aim of this study was to investigate the associations of osteosarcopenic obesity (OSO) and its components with complete blood cell count-derived inflammation indices. METHODS: In this cross-sectional study, data of 648 participants aged ≥60 years (men/women: 232/416, mean age: 67.21 ± 6.40 years) were collected from January 2018 to December 2020. Areal bone mineral density and body fat percentage were used to define osteopenia/osteoporosis and obesity, respectively. The criteria of the 2019 Asian Working Group for Sarcopenia were used to diagnose sarcopenia. Based on the number of these conditions, participants were divided into four groups: OSO/0, OSO/1, OSO/2, and OSO/3. Logistic regression analysis was conducted to identify associations between blood cell count-derived inflammation indices and the number of disorders with abnormal body composition. RESULTS: Systemic inflammation response index (SIRI), white blood cells, neutrophil-to-lymphocyte ratio (NLR), aggregate inflammation systemic index (AISI), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) showed statistically significant differences among the four groups (P < 0.05). Unlike in the OSO/0 group, in all other groups, AISI, SIRI, PLR, and NLR were significantly associated with increased likelihood of having multiple disorders with abnormal body composition after adjustment for confounders (P < 0.0001 for all). However, LMR showed an inverse correlation with the number of these conditions (P < 0.05). CONCLUSION: Higher SIRI, AISI, NLR, and PLR values and lower LMR values are closely associated with OSO and its individual components-osteoporosis, sarcopenia, and obesity-in older adults, suggesting that the value of these indices in the evaluation of OSO warrants further investigation.

KLF16 enhances stress tolerance of colorectal carcinomas by modulating nucleolar homeostasis and translational reprogramming.

Translational reprogramming is part of the unfolded protein response (UPR) during endoplasmic reticulum (ER) stress, which acts to the advantage of cancer growth and development in different stress conditions, but the mechanism of ER stress-related translational reprogramming in colorectal carcinoma (CRC) progression remains unclear. Here, we identified that Krüppel-like factor 16 (KLF16) can promote CRC progression and stress tolerance through translational reprogramming. The expression of KLF16 was upregulated in CRC tissues and associated with poor prognosis for CRC patients. We found that ER stress inducers can recruit KLF16 to the nucleolus and increase its interaction with two essential proteins for nucleolar homeostasis: nucleophosmin1 (NPM1) and fibrillarin (FBL). Moreover, knockdown of KLF16 can dysregulate nucleolar homeostasis in CRC cells. Translation-reporter system and polysome profiling assays further showed that KLF16 can effectively promote cap-independent translation of ATF4, which can enhance ER-phagy and the proliferation of CRC cells. Overall, our study unveils a previously unrecognized role for KLF16 as an ER stress regulator through mediating translational reprogramming to enhance the stress tolerance of CRC cells and provides a potential therapeutic vulnerability.

A novel colorimetric indicator film based on watermelon peel pectin and anthocyanins from purple cabbage for monitoring mutton freshness.

Novel films based on watermelon peel pectin (WMP) incorporated with purple cabbage extract (PCE) were developed for monitoring the freshness of mutton. The FTIR result showed that WMP and PCE interacted through hydrogen bonds. Low PCE content (≤1.5%) could be well dispersed in the film matrix, resulting in an enhancement in light transmittance, mechanical properties, barrier properties, and thermal stability. Excessive addition of PCE destroyed the compact structure of the film and decreased the comprehensive properties. The antioxidant and antimicrobial activity of WMP/PCE films were proportional to the amount of incorporated PCE. Moreover, the color of the film deepened as the PCE content increased. The film had excellent color stability and pH response properties. The WMP/PCE1.5 film color varied from mauve to baby blue according to the quality of mutton (fresh to spoiled). Our results suggested that the WMP/PCE film might have great potential for monitoring the freshness of mutton.

Effects of caspase activity of yak meat and internal environment changing during aging.

The objective of this study was to investigate the protease family caspases in skeletal muscle and their potential contribution to postmortem proteolysis and meat tenderization. Nine yaks were slaughtered, and samples of Longissimus dorsal were injected with AC-DEVD-CHO at a ratio of 1:1 (w/v) and then stored at 4 °C for 2, 6, 12, 24, 72, and 120 h. Results indicate that the morphological changes of the muscle fibers are significantly obstructed, which is not conducive to the subsequent degradation of proteins. After inhibiting the activity of Caspase- 3, the activity of Caspase-8 and 9 and the energy metabolism was affected. In the case of without inhibition of caspase, the pH value decreased and then increased. The meat color and the water retention are better, the muscle fiber skeleton protein degradation is remarkable, the tenderness is improved. Furthermore, yak meat tenderness was improved by apoptotic pathway during aging.

Study on the Multitarget Mechanism and Active Compounds of Essential Oil from Artemisia argyi Treating Pressure Injuries Based on Network Pharmacology.

In order to comprehensively explore multitarget mechanism and key active compounds of Artemisia argyi essential oil (AAEO) in the treatment of pressure injuries (PIs), we analyzed the biological functions and pathways involved in the intersection targets of AAEO and PIs based on network pharmacology, and the affinity of AAEO active compounds and core targets was verified by molecular docking finally. In our study, we first screened 54 effective components according to the relative content and biological activity. In total, 103 targets related to active compounds of AAEO and 2760 targets associated with PIs were obtained, respectively, and 50 key targets were overlapped by Venny 2.1.0. The construction of key targets-compounds network was achieved by the STRING database and Cytoscape 3.7.2 software. GO analysis from Matespace shows that GO results are mainly enriched in biological processes, including adrenergic receptor activity, neurotransmitter clearance, and neurotransmitter metabolic process. KEGG analysis by the David and Kobas website shows that the key targets can achieve the treatment on PIs through a pathway in cancer, PI3K-Akt signaling pathway, human immunodeficiency virus 1 infection, MAPK signaling pathway, Wnt signaling pathway, etc. In addition, molecular docking results from the CB-Dock server indicated that active compounds of AAEO had good activity docking with the first 10 key targets. In conclusion, the potential targets and regulatory molecular mechanisms of AAEO in the treatment of PIs were analyzed by network pharmacology and molecular docking. AAEO can cure PIs through the synergistic effect of multicomponent, multitarget, and multipathway, providing a theoretical basis and new direction for further study.

Comparison of the prognosis of four different surgical strategies for proximal gastric cancer: a network meta-analysis.

BACKGROUND: There is controversy regarding the long-term prognosis and short-term postoperative complications of different surgical strategies for proximal gastric cancer (PGC). METHODS: We searched for articles published in Embase (Ovid), Medline (Ovid), PubMed, Cochrane Library, and Web of Science between January 1, 1990, and February 1, 2021. We screened out the literature comparing different surgical strategies. We then evaluated the long-term and short-term outcome of different surgical strategies using a network meta-analysis, which summarizes the hazard ratio, odds ratio, mean difference, and 95% confidence interval. RESULTS: There were no significant differences between different surgical strategies for 5-year overall survival (OS), anastomotic leakage, or weight loss after 1 year. Compared with total gastrectomy with Roux-en-Y reconstruction (TG-RY) and proximal gastrectomy with double tract reconstruction (PG-DTR), the proximal gastrectomy with esophagogastrostomy (PG-EG) strategy significantly increased the incidence of reflux esophagitis; and the operation time and blood loss of the PG-EG strategy were significantly less than those of the other surgical strategies. The anastomotic stenosis rates of the PG-EG and proximal gastrectomy with jejunum interstitial (PG-JI) strategies were significantly higher than those of TG-RY and PG-DTR; the hemoglobin level after 1 year for the PG-DTR strategy was significantly higher than that of the TG-RY strategy. CONCLUSION: Our comprehensive literature research found that different surgical strategies had no significant difference in the long-term survival of PGC, but the incidence of reflux esophagitis and anastomotic stenosis after PG-DTR and TG-RY was significantly reduced.

PPIP5K2 promotes colorectal carcinoma pathogenesis through facilitating DNA homologous recombination repair.

Colorectal carcinoma (CRC) is the second most deadly cancer worldwide. Therapies that take advantage of DNA repair defects have been explored in various tumors but not yet systematically in CRC. Here, we found that Diphosphoinositol Pentakisphosphate Kinase 2 (PPIP5K2), an inositol pyrophosphate kinase, was highly expressed in CRC and associated with a poor prognosis of CRC patients. In vitro and in vivo functional studies demonstrated that PPIP5K2 could promote the proliferation and migration ability of CRC cells independent of its inositol pyrophosphate kinase activity. Mechanically, S1006 dephosphorylation of PPIP5K2 could accelerate its dissociation with 14-3-3 in the cytoplasm, resulting in more nuclear distribution. Moreover, DNA damage treatments such as doxorubicin (DOX) or irradiation (IR) could induce nuclear translocation of PPIP5K2, which subsequently promoted homologous recombination (HR) repair by binding and recruiting RPA70 to the DNA damage site as a novel scaffold protein. Importantly, we verified that S1006 dephosphorylation of PPIP5K2 could significantly enhance the DNA repair ability of CRC cells through a series of DNA repair phenotype assays. In conclusion, PPIP5K2 is critical for enhancing the survival of CRC cells via facilitating DNA HR repair. Our findings revealed an unrecognized biological function and mechanism model of PPIP5K2 dependent on S1006 phosphorylation and provided a potential therapeutic target for CRC patients.

Design of Two-Step Random Access Procedure for URLLC Applications.

The International Telecommunication Union has required that the control plane (C-plane) latency in the fifth generation (5G) ultra-reliable low-latency communication (URLLC) application scenarios should not exceed 20 ms and encouraged technical innovation to further reduce it to less than 10 ms. However, the average C-plane latency in the fourth generation (4G) Long Term Evolution-Advanced (LTE-A) system is 80 ms. Such a high latency is because of the execution of the contention-based random access procedure (RAP). In this paper, we simplify the conventional contention-based RAP from 4 to 2 steps. Furthermore, utilization of demodulation reference signal for representing the UE ID and reservation of preambles for URLLC users significantly reduces the proposed 2-step RAP latency. From the perspectives of fixing the number of URLLC users and fixing the number of preambles reserved for URLLC users, simulation results show the percentage of successes for the 2-step RAP is 83.81% and 71.83% higher than that of the 4-step RAP, respectively. Consequently, the 10 ms latency requirement of the 5G URLLC is achieved.