A shock flash breaking out of a dusty red supergiant.

Shock-breakout emission is light that arises when a shockwave, generated by the core-collapse explosion of a massive star, passes through its outer envelope. Hitherto, the earliest detection of such a signal was at several hours after the explosion1, although a few others had been reported2-7. The temporal evolution of early light curves should provide insights into the shock propagation, including explosion asymmetry and environment in the vicinity, but this has been hampered by the lack of multiwavelength observations. Here we report the instant multiband observations of a type II supernova (SN 2023ixf) in the galaxy M101 (at a distance of 6.85 ± 0.15 Mpc; ref. 8), beginning at about 1.4 h after the explosion. The exploding star was a red supergiant with a radius of about 440 solar radii. The light curves evolved rapidly, on timescales of 1-2 h, and appeared unusually fainter and redder than predicted by the models9-11 within the first few hours, which we attribute to an optically thick dust shell before it was disrupted by the shockwave. We infer that the breakout and perhaps the distribution of the surrounding dust were not spherically symmetric.

Tumor-derived exosomal lincRNA ROR promotes angiogenesis in nasopharyngeal carcinoma.

Long intergenic noncoding RNAs (lincRNAs) are expressed aberrantly in several malignancies, including nasopharyngeal carcinoma (NPC), where linc-ROR expression was found to be elevated. Being a hallmark of malignant tumors, angiogenesis has prompted us to investigate the impact of linc-ROR on NPC angiogenesis. This study demonstrates that linc-ROR is substantially expressed in serum exosomes from NPC and can be taken up by HUVECs. Using qRT-PCR, the CCK8 test, the transwell migration assay, the wound healing assay, and the tube formation assay, we demonstrated that linc-ROR increases proliferation, migration, and angiogenesis in vitro. Similar to prior research, our results have shown that linc-ROR can stimulate tumor angiogenesis in the zebrafish model. Thus, the p-AKT/p-VEGFR2 pathway is the mechanism by which linc-ROR affects the aforementioned biological activities. By stimulating angiogenesis, linc-ROR appears to play a significant role in the course of NPC and could account for a therapeutic target.

SARS-CoV-2 infection-induced immune responses: Friends or foes?

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging coronavirus that belongs to the ß-genus, causing the outbreak of coronavirus disease 19 (COVID-19). SARS-CoV-2 infection can stimulate a pronounced immune response in the host, which embodies in the decrease of lymphocytes and aberrant increase of cytokines in COVID-19 patients. SARS-CoV-2 RNA and proteins interact with various pattern recognition receptors that switch on antiviral immune responses to regulate viral replication and spreading within the host in vivo. However, overactive and impaired immune responses also cause immune damage and subsequent tissue inflammation. This article focuses on the dual roles of immune system during SARS-CoV-2 infection, providing a theoretical basic for identifying therapeutic targets in a situation with an unfavourable immune reaction.

A revised mechanism for the activation of complement C3 to C3b: a molecular explanation of a disease-associated polymorphism.

The solution structure of complement C3b is crucial for the understanding of complement activation and regulation. C3b is generated by the removal of C3a from C3. Hydrolysis of the C3 thioester produces C3u, an analog of C3b. C3b cleavage results in C3c and C3d (thioester-containing domain; TED). To resolve functional questions in relation to C3b and C3u, analytical ultracentrifugation and x-ray and neutron scattering studies were used with C3, C3b, C3u, C3c, and C3d, using the wild-type allotype with Arg(102). In 50 mm NaCl buffer, atomistic scattering modeling showed that both C3b and C3u adopted a compact structure, similar to the C3b crystal structure in which its TED and macroglobulin 1 (MG1) domains were connected through the Arg(102)-Glu(1032) salt bridge. In physiological 137 mm NaCl, scattering modeling showed that C3b and C3u were both extended in structure, with the TED and MG1 domains now separated by up to 6 nm. The importance of the Arg(102)-Glu(1032) salt bridge was determined using surface plasmon resonance to monitor the binding of wild-type C3d(E1032) and mutant C3d(A1032) to immobilized C3c. The mutant did not bind, whereas the wild-type form did. The high conformational variability of TED in C3b in physiological buffer showed that C3b is more reactive than previously thought. Because the Arg(102)-Glu(1032) salt bridge is essential for the C3b-Factor H complex during the regulatory control of C3b, the known clinical associations of the major C3S (Arg(102)) and disease-linked C3F (Gly(102)) allotypes of C3b were experimentally explained for the first time.

Monocytes from patients with osteoarthritis display increased osteoclastogenesis and bone resorption: the In Vitro Osteoclast Differentiation in Arthritis study.

OBJECTIVE: To compare the osteoclastogenic capacity of peripheral blood mononuclear cells (PBMCs) from patients with osteoarthritis (OA) to that of PBMCs from self-reported normal individuals. METHODS: PBMCs from 140 patients with OA and 45 healthy donors were assayed for CD14+ expression and induced to differentiate into osteoclasts over 3 weeks in vitro. We assessed the number of osteoclasts, their resorptive activity, osteoclast apoptosis, and expression of the following cytokine receptors: RANK, interleukin-1 receptor type I (IL-1RI), and IL-1RII. A ridge logistic regression classifier was developed to discriminate OA patients from controls. RESULTS: PBMCs from OA patients gave rise to more osteoclasts that resorbed more bone surface than did PBMCs from controls. The number of CD14+ precursors was comparable in both groups, but there was less apoptosis in osteoclasts obtained from OA patients. Although no correlation was found between osteoclastogenic capacity and clinical or radiographic scores, levels of IL-1RI were significantly lower in cultures from patients with OA than in cultures from controls. Osteoclast apoptosis and expression levels of IL-1RI and IL-1RII were used to build a multivariate predictive model for OA. CONCLUSION: During 3 weeks of culture under identical conditions, monocytes from patients with OA display enhanced capacity to generate osteoclasts compared to cells from controls. Enhanced osteoclastogenesis is accompanied by increased resorptive activity, reduced osteoclast apoptosis, and diminished IL-1RI expression. These findings support the possibility that generalized changes in bone metabolism affecting osteoclasts participate in the pathophysiology of OA.

Effectively solve the obstacle in the old residential building energy-saving renovation from the perspective of a four-party evolutionary game.

Although the government highly focuses on old residential building energy-saving renovation (ORBESR), many hinders still exist and the efficiency of it is still low. This paper proposes a four-party evolutionary game model to study the impact of relative stakeholders' choices, involving developers, residents, neighborhood councils, and governments. Using this model, this paper studies what influences the conflicts between developers and residents take on the efficiency of ORBESR. In addition, what influence the residents, neighborhood councils, and developers' strategies will take on the ORBESR under the condition of evolutionary stability strategy. This paper finally concludes that governments could propose high penalties first to accelerate the stability of the system, then suitable subsidies to relieve the financial burden and to achieve high efficiency. The governments could provide a suitable plan for residents' investment to promote residents' participation. The neighborhood councils arouse the ways and facilities to help residents understand and participate in the ORBESR and try to solve the conflicts between developers and residents can improve the residents' participation and the developers' willingness to implement the ORBESR.

The m6A demethylases FTO and ALKBH5 aggravate the malignant progression of nasopharyngeal carcinoma by coregulating ARHGAP35.

N6-methyladenosine (m6A) is an RNA modification that can be removed by demethylases [fat mass and obesity-associated protein (FTO) and AlkB homolog 5 (ALKBH5)], which regulate gene expression and cell function. We show that m6A levels and m6A demethylase levels are altered in nasopharyngeal carcinoma (NPC) tissues vs. normal tissues. High FTO and ALKBH5 predict a poor prognosis in NPC patients. Silencing FTO and ALKBH5 inhibited the malignant behavior of patient-derived NPC cells in a short time. However, as time progressed, the inhibitory effect of FTO or ALKBH5 was weakened, and the cosilencing of FTO and ALKBH5 maintained a better inhibitory effect. Combined transcriptome and m6A-seq analysis revealed a downstream target gene that was jointly regulated by FTO and ALKBH5 in NPC, and ARHGAP35 was chosen to do further study. The synergistic silencing of FTO and ALKBH5 increased the methylation level on the mRNA CDS of a new transcription factor (ARHGAP35) and positively regulate the protein coding capacity and mRNA stability of ARHGAP35, thus leading to increased expression of ARHGAP35 and inhibition of the malignant phenotype of tumor cells. Our study revealed that the growth and metastasis of NPC can be stably inhibited through synergistic silencing of the demethylases FTO and ALKBH5, which play a positive role in the treatment of NPC by regulating the downstream transcript ARHGAP35 and increasing its m6A level.

Ophiocordyceps sinensis preparations combined with the renin-angiotensin system inhibitor for diabetic kidney disease treatment: an umbrella review of systematic reviews and network meta-analysis.

Aims: This study aimed to synthesize the evidence of the comparative effectiveness and safety of Ophiocordyceps sinensis (OS) preparations combined with renin-angiotensin system inhibitors (RASi) for diabetic kidney disease (DKD). Methods: Eight databases were searched from their inception to May 2023. Systematic reviews (SRs) of OS preparations combined with RASi for DKD were identified. Randomized controlled trials (RCTs) from the included SRs and additional searching were performed for data pooling. Cochrane risk-of-bias 2 (RoB 2) tool and AMSTAR 2 were used to evaluate the methodological quality of RCTs and SRs, respectively. A Bayesian network meta-analysis was performed to compare the add-on effect and safety of OS preparations for DKD. The certainty of evidence was graded using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Results: Fourteen SRs were included, whose methodological quality was assessed as high (1/14) or critically low (13/14). After combining additional searching, 157 RCTs were included, involving 13,143 participants. The quality of the RCTs showed some concerns (155/157) or high risk (2/157). Jinshuibao capsules and tablets, Bailing capsules and tablets, and Zhiling capsules were evaluated. Compared to RASi, adding either of the OS capsular preparations resulted in a decreased 24-h urinary total protein levels. OS preparations ranked differently in each outcome. Jinshuibao capsules plus RASi were beneficial in reducing urinary protein, serum creatinine, serum urea nitrogen, and blood glucose levels, with moderate-certainty evidence. No serious adverse events were observed after adding OS to RASi. Conclusion: Combining OS capsular preparations with RASi appeared to be associated with decreased urinary total protein levels in DKD patients. Further high-quality studies are needed to confirm. Systematic Review Registration: INPASY202350066.

Luteolin inhibition of V-ATPase a3-d2 interaction decreases osteoclast resorptive activity.

V-ATPase-mediated acid secretion is required for osteoclast bone resorption. Osteoclasts are enriched in V-ATPase a3 and d2 subunit isoforms, and disruption of either of their genes impairs bone resorption. Using purified fusion proteins of a3 N-terminal domain (NTa3) and full-length d subunits we determined in a solid-phase binding assay that half-maximal binding of d1 or d2 to immobilized NTa3 occurs at 3.1 ± 0.4 or 3.6 ± 0.6 nM, respectively, suggesting equally high-affinity interactions. A high-throughput modification of this assay was then used to screen chemical libraries for a3-d2 interaction inhibitors, and luteolin, a naturally occurring flavonoid, was identified, with half-maximal inhibition at 2.4 ± 0.9 µM. Luteolin did not significantly affect NIH/3T3 or RAW 264.7 cell viability, nor did it affect cytokine-induced osteoclastogenesis of RAW 264.7 cells or bone marrow mononuclear cells at concentrations ≤ 40 µM. Luteolin inhibited osteoclast bone resorption with an EC(50) of approximately 2.5 µM, without affecting osteoclast actin ring formation. Luteolin-treated osteoclasts produced deeper resorption pits, but with decreased surface area, resulting in overall decreased pit volume. Luteolin did not affect transcription, or protein levels, of V-ATPase subunits a3, d2, and E, or V(1) V(0) assembly. Previous work has shown that luteolin can be effective in reducing bone resorption, and our studies suggest that this effect of luteolin may be through disruption of osteoclast V-ATPase a3-d2 interaction. We conclude that the V-ATPase a3-d2 interaction is a viable target for novel anti-resorptive therapeutics that potentially preserve osteoclast-osteoblast signaling important for bone remodeling.

ROS/Electro Dual-Reactive Nanogel for Targeting Epileptic Foci to Remodel Aberrant Circuits and Inflammatory Microenvironment.

Medicinal treatment against epilepsy is faced with intractable problems, especially epileptogenesis that cannot be blocked by clinical antiepileptic drugs (AEDs) during the latency of epilepsy. Abnormal circuits of neurons interact with the inflammatory microenvironment of glial cells in epileptic foci, resulting in recurrent seizures and refractory epilepsy. Herein, we have selected phenytoin (PHT) as a model drug to derive a ROS-responsive and consuming prodrug, which is combined with an electro-responsive group (sulfonate sodium, SS) and an epileptic focus-recognizing group (α-methyl-l-tryptophan, AMT) to form hydrogel nanoparticles (i.e., a nanogel). The nanogel will target epileptic foci, release PHT in response to a high concentration of reactive oxygen species (ROS) in the microenvironment, and inhibit overexcited circuits. Meanwhile, with the clearance of ROS, the nanogel can also reduce oxidative stress and alleviate microenvironment inflammation. Thus, a synergistic regulation of epileptic lesions will be achieved. Our nanogel is expected to provide a more comprehensive strategy for antiepileptic treatment.

Dipeptide-1 modified nanostructured lipid carrier-based hydrogel with enhanced skin retention and topical efficacy of curcumin.

Topical administration of curcumin (CUR), a natural polyphenol with potent anti-inflammation and analgesic activities, provides a potential approach for local skin diseases. However, the drug delivery efficiency is highly limited by skin barriers and poor bioavailability of CUR. Herein, we propose hydrogel containing CUR-encapsulated dipeptide-1-modified nanostructured lipid carriers (CUR-DP-NLCs gel) to enhance topical drug delivery, and improve the topical therapeutic effect. The prepared CUR-DP-NLCs were characterized and were suitably dispersed into the Pluronic F127 hydrogel for topical application. The optimized CUR-DP-NLCs had a particle size of 152.6 ± 3.47 nm, a zeta potential of -33.1 ± 1.46 mV, an entrapment efficiency of 99.83 ± 0.14%, and a spherical morphology. X-ray diffraction (XRD) studies confirmed that CUR was successfully entrapped by the NLCs in an amorphous form. CUR-DP-NLCs gel exhibited sustained release over 48 h and significantly increased the skin retention of CUR. In vitro skin retention of CUR with CUR-DP-NLCs gel was 2.14 and 2.85 times higher than that of unmodified NLCs gel and free CUR, respectively. Fluorescence microscopy imaging revealed the formed nanoparticles accumulated in the hair follicles with prolonged retention time to form a drug reservoir. The hematoxylin-eosin staining showed that CUR-DP-NLCs gel could change the microstructure of skin layers and disturb the skin barriers. After topical administration to mice, CUR-DP-NLCs gel showed better analgesic and anti-inflammatory activities with no potentially hazardous skin irritation. These results concluded that CUR-DP-NLCs gel is a promising strategy to increase topical drug delivery of CUR in the treatment of local skin diseases.

ROS-removing nano-medicine for navigating inflammatory microenvironment to enhance anti-epileptic therapy.

As a neurological disorder in the brain, epilepsy is not only associated with abnormal synchronized discharging of neurons, but also inseparable from non-neuronal elements in the altered microenvironment. Anti-epileptic drugs (AEDs) merely focusing on neuronal circuits frequently turn out deficient, which is necessitating comprehensive strategies of medications to cover over-exciting neurons, activated glial cells, oxidative stress and chronic inflammation synchronously. Therefore, we would report the design of a polymeric micelle drug delivery system that was functioned with brain targeting and cerebral microenvironment modulation. In brief, reactive oxygen species (ROS)-sensitive phenylboronic ester was conjugated with poly-ethylene glycol (PEG) to form amphiphilic copolymers. Additionally, dehydroascorbic acid (DHAA), an analogue of glucose, was applied to target glucose transporter 1 (GLUT1) and facilitate micelle penetration across the blood‒brain barrier (BBB). A classic hydrophobic AED, lamotrigine (LTG), was encapsulated in the micelles via self-assembly. When administrated and transferred across the BBB, ROS-scavenging polymers were expected to integrate anti-oxidation, anti-inflammation and neuro-electric modulation into one strategy. Moreover, micelles would alter LTG distribution in vivo with improved efficacy. Overall, the combined anti-epileptic therapy might provide effective opinions on how to maximize neuroprotection during early epileptogenesis.

Low-Pass Genome Sequencing-Based Detection of Paternity: Validation in Clinical Cytogenetics.

Submission of a non-biological parent together with a proband for genetic diagnosis would cause a misattributed parentage (MP), possibly leading to misinterpretation of the pathogenicity of genomic variants. Therefore, a rapid and cost-effective paternity/maternity test is warranted before genetic testing. Although low-pass genome sequencing (GS) has been widely used for the clinical diagnosis of germline structural variants, it is limited in paternity/maternity tests due to the inadequate read coverage for genotyping. Herein, we developed rapid paternity/maternity testing based on low-pass GS with trio-based and duo-based analytical modes provided. The optimal read-depth was determined as 1-fold per case regardless of sequencing read lengths, modes, and library construction methods by using 10 trios with confirmed genetic relationships. In addition, low-pass GS with different library construction methods and 1-fold read-depths were performed for 120 prenatal trios prospectively collected, and 1 trio was identified as non-maternity, providing a rate of MP of 0.83% (1/120). All results were further confirmed via quantitative florescent PCR. Overall, we developed a rapid, cost-effective, and sequencing platform-neutral paternity/maternity test based on low-pass GS and demonstrated the feasibility of its clinical use in confirming the parentage for genetic diagnosis.

Predicting the risk of acute respiratory failure among asthma patients-the A2-BEST2 risk score: a retrospective study.

Objectives: Acute respiratory failure (ARF) is a common complication of bronchial asthma (BA). ARF onset increases the risk of patient death. This study aims to develop a predictive model for ARF in BA patients during hospitalization. Methods: This was a retrospective cohort study carried out at two large tertiary hospitals. Three models were developed using three different ways: (1) the statistics-driven model, (2) the clinical knowledge-driven model, and (3) the decision tree model. The simplest and most efficient model was obtained by comparing their predictive power, stability, and practicability. Results: This study included 398 patients, with 298 constituting the modeling group and 100 constituting the validation group. Models A, B, and C yielded seven, seven, and eleven predictors, respectively. Finally, we chose the clinical knowledge-driven model, whose C-statistics and Brier scores were 0.862 (0.820-0.904) and 0.1320, respectively. The Hosmer-Lemeshow test revealed that this model had good calibration. The clinical knowledge-driven model demonstrated satisfactory C-statistics during external and internal validation, with values of 0.890 (0.815-0.965) and 0.854 (0.820-0.900), respectively. A risk score for ARF incidence was created: The A2-BEST2 Risk Score (A2 (area of pulmonary infection, albumin), BMI, Economic condition, Smoking, and T2(hormone initiation Time and long-term regular medication Treatment)). ARF incidence increased gradually from 1.37% (The A2-BEST2 Risk Score ≤ 4) to 90.32% (A2-BEST2 Risk Score ≥ 11.5). Conclusion: We constructed a predictive model of seven predictors to predict ARF in BA patients. This predictor's model is simple, practical, and supported by existing clinical knowledge.

A novel quantitative model based on gross tumor volume corresponding to anatomical distribution measured with multidetector computed tomography to determine the resectability of non­distant metastatic esophageal squamous cell carcinoma.

It is important to accurately determine the resectability of thoracic esophageal squamous cell carcinoma (ESCC) for treatment decision-making. Previous studies have revealed that the CT-derived gross tumor volume (GTV) is associated with the staging of ESCC. The present study aimed to explore whether the anatomical distribution-based GTV of non-distant metastatic thoracic ESCC measured using multidetector computed tomography (MDCT) could quantitatively determine the resectability. For this purpose, 473 consecutive patients with biopsy-confirmed non-distant metastatic thoracic ESCC who underwent contrast-enhanced CT were randomly divided into a training cohort (TC; 376 patients) and validation cohort (VC; 97 patients). GTV was retrospectively measured using MDCT. Univariate and multivariate analyses were performed to identify the determinants of the resectability of ESCC in the TC. Receiver operating characteristic (ROC) analysis was performed to clarify whether anatomical distribution-based GTV could help quantitatively determinate resectability. Unweighted Cohen's Kappa tests in VC were used to assess the performance of the previous models. Univariate analysis demonstrated that sex, anatomic distribution, cT stage, cN stage and GTV were related to the resectability of ESCC in the TC (all P<0.05). Multivariate analysis revealed that GTV [P<0.001; odds ratio (OR) 1.158] and anatomic distribution (P=0.027; OR, 1.924) were independent determinants of resectability. ROC analysis revealed that the GTV cut-offs for the determination of the resectability of the upper, middle and lower thoracic portions were 23.57, 22.89 and 22.58 cm3, respectively, with areas under the ROC curves of >0.9. Unweighted Cohen's Kappa tests revealed an excellent performance of the ROC models in the upper, middle and lower thoracic portions with Cohen k-values of 0.913, 0.879 and 0.871, respectively. On the whole, the present study demonstrated that GTV and the anatomic distribution of non-distant metastatic thoracic ESCC may be independent determinants of resectability, and anatomical distribution-based GTV can effectively be used to quantitatively determine resectability.

Analytical ultracentrifugation combined with X-ray and neutron scattering: Experiment and modelling.

Analytical ultracentrifugation and solution scattering provide different multi-parameter structural and compositional information on proteins. The joint application of the two methods supplements high resolution structural studies by crystallography and NMR. We summarise the procedures required to obtain equivalent ultracentrifugation and X-ray and neutron scattering data. The constrained modelling of ultracentrifugation and scattering data is important to confirm the experimental data analysis and yields families of best-fit molecular models for comparison with crystallography and NMR structures. This modelling of ultracentrifugation and scattering data is described in terms of starting models, their conformational randomisation in trial-and-error fits, and the identification of the final best-fit models. Seven applications of these methods are described to illustrate the current state-of-the-art. These include the determination of antibody solution structures (the human IgG4 subclass, and oligomeric forms of human IgA and its secretory component), the solution structures of the complement proteins of innate immunity (Factor H and C3/C3u) and their interactions with macromolecular ligands (C-reactive protein), and anionic polysaccharides (heparin). Complementary features of joint ultracentrifugation and scattering experiments facilitate an improved understanding of crystal structures (illustrated for C3/C3u, C-reactive protein and heparin). If a large protein or its complex cannot be crystallised, the joint ultracentrifugation-scattering approach provides a means to obtain an overall macromolecular structure.

Study on the Effect of Self-Made Lifei Dingchuan Decoction Combined with Western Medicine on Cough Variant Asthma.

Aims: To observe the clinical efficacy of self-made Lifei Dingchuan decoction combined with western medicine in the treatment of cough variant asthma (phlegm-heat accumulation in the lung syndrome). Materials and Methods: The clinical data of 90 patients with cough variant asthma who were hospitalized in the Department of Respiratory Medicine of our hospital from January 2020 to April 2022 were selected as the research objects, and they were equally divided into the observation group and the reference group according to different treatment methods, 45 cases in each group. The group was treated with traditional montelukast sodium chewable tablet and salmeterol fluticasone mixed powder inhalation, and the observation group was treated with self-made Lifei Dingchuan decoction on the basis of the control group, saturation, pH, partial pressure of oxygen in arterial blood, partial pressure of carbon dioxide, length of stay, and hospitalization costs. Results: After the patients underwent self-made Lifei Dingchuan decoction, there were significant differences between the observation group and the reference group in terms of heart rate, respiratory rate, blood oxygen saturation, pH value, arterial blood oxygen partial pressure, carbon dioxide partial pressure, and within the group. There was a statistical difference (P < 0.05). The adverse reactions in patients with cough variant asthma after treatment showed that the red throat, shortness of breath, chest tightness, and dry mouth in the observation group were significantly different from those in the control group (P < 0.05). After investigation, follow-up, and statistics, the hospitalization time, hospitalization cost, asthma exacerbation control time, effective rate, and recurrence rate were compared between the two groups, and the differences between the two groups were statistically significant (P < 0.05). Conclusion: The study on the clinical efficacy and low hospitalization cost of the self-prepared lung and asthma-restorative soup in patients with cough variant asthma significantly improved the patients' arterial oxygen saturation, acid-base value, arterial partial pressure of oxygen, and partial pressure of carbon dioxide and effectively controlled the heart rate and respiratory rate with high safety, which is worth further promotion.

Gross tumor volume of adenocarcinoma of esophagogastric junction corresponding to cT and cN stages measured with computed tomography to quantitatively determine resectabiliy: A case control study.

Purpose: To determine whether gross tumor volume (GTV) of adenocarcinoma of esophagogastric junction (AEG) corresponding to cT and cN stages measured on CT could help quantitatively determine resectability. Materials and methods: 343 consecutive patients with AEG, including 279 and 64 randomly enrolled in training cohort (TC) and validation cohort (VC), respectively, underwent preoperative contrast-enhanced CT. Univariate and multivariate analyses for TC were performed to determine factors associated with resectability. Receiver operating characteristic (ROC) analyses were to determine if GTV corresponding to cT and cN stages could help determine resectability. For VC, Cohen's Kappa tests were to assess performances of the ROC models. Results: cT stage, cN stage and GTV were independently associated with resectability of AEG with odds ratios of 4.715, 4.534 and 1.107, respectively. For differentiating resectable and unresectable AEG, ROC analyses showed that cutoff GTV of 32.77 cm3 in stage cT1-4N0-3 with an area under the ROC curve (AUC) of 0.901. Particularly, cutoffs of 27.67 and 32.77 cm3 in stages cT3 and cT4 obtained AUC values of 0.860 and 0.890, respectively; and cutoffs of 27.09, 33.32 and 37.39 cm3 in stages cN1, cN2 and cN3 obtained AUC values of 0.852, 0.821 and 0.902, respectively. In VC, Cohen's Kappa tests verified that the ROC models had good performance in distinguishing between resectable and unresectable AEG (all Cohen's K values > 0.72). Conclusions: GTV, cT and cN stages could be independent determinants of resectability of AEG. And GTV corresponding to cT and cN stages can help quantitatively determine resectability.

Ginsenoside Rb1 improves intestinal aging via regulating the expression of sirtuins in the intestinal epithelium and modulating the gut microbiota of mice.

Intestinal aging seriously affects the absorption of nutrients of the aged people. Ginsenoside Rb1 (GRb1) which has multiple functions on treating gastrointestinal disorders is one of the important ingredients from Ginseng, the famous herb in tradition Chinese medicine. However, it is still unclear if GRb1 could improve intestinal aging. To investigate the function and mechanism of GRb1 on improving intestinal aging, GRb1 was administrated to 104-week-old C57BL/6 mice for 6 weeks. The jejunum, colon and feces were collected for morphology, histology, gene expression and gut microbiota tests using H&E staining, X-gal staining, qPCR, Western blot, immunofluorescence staining, and 16S rDNA sequencing technologies. The numbers of cells reduced and the accumulation of senescent cells increased in the intestinal crypts of old mice, and administration of GRb1 could reverse them. The protein levels of CLDN 2, 3, 7, and 15 were all decreased in the jejunum of old mice, and administration of GRb1 could significantly increase them. The expression levels of Tert, Lgr5, mKi67, and c-Myc were all significantly reduced in the small intestines of old mice, and GRb1 significantly increased them at transcriptional or posttranscriptional levels. The protein levels of SIRT1, SIRT3, and SIRT6 were all reduced in the jejunum of old mice, and GRb1 could increase the protein levels of them. The 16S rDNA sequencing results demonstrated the dysbiosis of the gut microbiota of old mice, and GRb1 changed the composition and functions of the gut microbiota in the old mice. In conclusion, GRb1 could improve the intestinal aging via regulating the expression of Sirtuins family and modulating the gut microbiota in the aged mice.

A quantitative model based on gross tumor volume of gastric adenocarcinoma corresponding to N-stage measured at multidetector computed tomography for preoperative determination of resectability: A case control study.

Purpose: To develop and validate a quantitative model based on gross tumor volume (GTV) of gastric adenocarcinoma (GA) corresponding to N-stage measured at multidetector computed tomography (CT) for preoperative determination of resectability. Materials and methods: 493 consecutive patients with confirmed GA undergoing contrast-enhanced CT two weeks before treatments were randomly enrolled into the training cohort (TC, n = 271), internal validation cohort (IVC, n = 107) and external validation cohort (EVC, n = 115). GTV was measured on CT by multiplying sums of all tumor areas by section thickness. In TC, univariate and multivariate analyses were performed to select factors associated with resectability. Receiver operating characteristic (ROC) analysis was to determine if N-stage based GTV could identify resectability. In IVC and EVC, unweighted Cohen's Kappa tests were to evaluate performances of the ROC models. Results: According to univariate analysis, age, cT stage, cN stage and GTV were related to resectability in TC (all P-values < 0.05), and multivariate analysis suggested that cN stage and GTV were independent risk factors with odds ratios of 1.594 (95% confidence interval [CI]: 1.105-2.301) and 1.055 (95%CI: 1.035-1.076), respectively. ROC analysis in TC revealed the cutoffs of 21.81, 21.70 and 36.93 cm3 to differentiate between resectable and unresectable cancers in stages cN0-3, cN2 and cN3 with areas under the curves of more than 0.8, respectively, which was validated in IVC and EVC with average Cohen k-values of more than 0.72. Conclusions: GTV and cN stage can be independent risk factors of unresectable GA, and N-stage based GTV can help determine resectability.