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\"Functional Pavements is a collection of papers presented at the 6th Chinese-European Workshop (CEW) on Functional Pavement Design (Nanjing, China, October 18-21, 2020). The focus of the CEW series is on field tests, laboratory test methods and advanced analysis techniques, and cover analysis, material development and production, experimental characterization, design and construction of pavements. The main areas covered by the book include: Asphalt binders for flexible pavements Asphalt mixture evaluation and performance Pavement construction and maintenance Pavement Surface Properties and Vehicle Interaction Cementitious materials for rigid pavements Pavement geotechnics and environment Functional Pavements aims at contributing to the establishment of a new generation of pavement design methodologies in which rational mechanics principles, advanced constitutive models and advanced material characterization techniques shall constitute the backbone of the design process. The book will be much of interest to professionals, academics and practitioners in pavement engineering and related disciplines as it should assist them in providing improved road pavement infrastructure to their stakeholders.\"-- Provided by publisher.

The BA.1, BA.2, and BA.3 omicron subvariants of SARS-CoV-2 showed similar but substantial resistance to vaccine-induced and infection-induced serum neutralising activity.1,2 The new BA.2.12.1, BA.2.13, BA.4, and BA.5 omicron subvariants containing Leu452 substitutions show more infectious potential than BA.2.3 We examined neutralising activity against the BA.1, BA.2, BA.2.11, BA.2.12.1, BA.2.13, BA.4, and BA.5 omicron subvariants in serum from people who received BBIBP-CorV (Sinopharm) primary immunisation, people who received BBIBP-CorV or ZF2001 (Anhui Zhifei Longcom) boosters, and people with omicron breakthrough infections (appendix pp 4, 7). Using an in-house pseudovirus neutralisation assay we found that two BBIBP-CorV doses induced detectable neutralising antibodies against spike protein mutation D614G in 21 (84%) individuals, but neutralising activity against omicron subvariants (BA.1, BA.2, BA.2.11, BA.2.12.1, BA.2.13, and BA.4/BA.5) was not or only minimally detectable (appendix pp 2–3, 8). Neutralising activity against omicron subvariants was observed in 24–48% of people who received a BBIBP-CorV booster and 30–53% of people who received a ZF2001 booster (appendix pp 2–3, 9). [...]serum samples with neutralising antibody titres higher than the limit of detection (limit of detection was 30) against the omicron subvariants had lower neutralising activity, with a 4·6–17·1-times lower GMT than the GMT against D614G (appendix pp 2–3).

Self-assembling peptides (SAPs) have enormous potential in medical and biological applications, particularly noninvasive tumor therapy. SAPs self-assembly is governed by multiple non-covalent interactions and results in the formation of a variety of morphological features. SAPs can be assembled in a variety of ways, including chemical conjugation and physical encapsulation, to incorporate multiple bioactive motifs. Peptide-based nanomaterials are used for chemotherapy, delivery vehicles, immunotherapy, and noninvasive tumor therapies (e.g. photodynamic therapy) by employing the self-assembling properties of peptides. The recent increase of SAPs is almost entirely due to their excellent biocompatibility, responsiveness toward tumor microenvironment, multivalency, and structural versatility. Synergistic therapy is a more effective and powerful approach to treat the tumor. Notably, SAPs can be used to subtly combine various treatments. Importantly, SAPs are capable of subtly making the combination of various treatments. This review describes mechanisms of peptides self-assemble into various structures and their biomedical applications with a focus on possible treatments.

Additionally, BA.1, BA.2, BA.4/5, and BF.7 exhibited susceptibility to BA.2.76 breakthrough infection serum samples; however, BA.2.75 showed more resistance than BA.2 and BA.4/5 (figure E). [...]BA.2.75 is more resistant to breakthrough BF.7 infection neutralisation than BA.2 and BA.4/5. [...]comparisons showed that BA.5.1.2 breakthrough infections induced a broader antibody response against the tested subvariants and induced significantly higher geometric mean titres against BQ.1 and BQ.1.1 compared with delta, BA.1, BA.2.2, BA.2.76, or BF.7 breakthrough infections (figure; appendix p 7). Omicron subvariants BQ.1 and BQ.1.1 with increased resistance to neutralising antibodies can pose a challenge to immunity induced by vaccination or infection and render therapeutic monoclonal antibodies ineffective.3–6 Our results suggest that BQ.1 and BQ.1.1 extensively, but incompletely, escape omicron subvariant breakthrough infection neutralisation, including the most recent BA.5.1.2, BA.2.76, and BF.7 infections.

Oxidative stress is an important pathogenic factor in ulcerative colitis (UC) and colitis-associated colorectal cancer (CAC), further impairing the entire colon. Intestinal epithelial cells (IECs) are crucial components of innate immunity and play an important role in maintaining intestinal barrier function. Recent studies have indicated that microRNA-222-3p (miR-222-3p) is increased in colon of UC and colorectal cancer (CRC) patients, and miR-222-3p is a crucial regulator of oxidative stress. However, whether miR-222-3p influences IEC oxidative stress in UC and CAC remains unknown. This study investigated the effect of miR-222-3p on the regulation of IEC oxidative stress in UC and CAC. An in vitro inflammation model was established in NCM460 colonic cells, mouse UC and CAC models were established in vivo , and IECs were isolated. The biological role and mechanism of miR-222-3p-mediated oxidative stress in UC and CAC were determined. We demonstrated that miR-222-3p expression was notably increased in dextran sulfate sodium (DSS)-induced NCM460 cells and IECs from UC and CAC mice. In vitro , these results showed that the downregulation of miR-222-3p reduced oxidative stress, caspase-3 activity, IL-1β and TNF-α in DSS-induced NCM460 cells. We further identified BRG1 as the target gene of miR-222-3p, and downregulating miR-222-3p alleviated DSS-induced oxidative injury via promoting BRG1-mediated activation Nrf2/HO-1 signaling in NCM460 cells. The in vivo results demonstrated that inhibiting miR-222-3p in IECs significantly relieved oxidative stress and inflammation in the damaged colons of UC and CAC mice, as evidenced by decreases in ROS, MDA, IL-1β and TNF-α levels and increases in GSH-Px levels. Our study further demonstrated that inhibiting miR-222-3p in IECs attenuated oxidative damage by targeting BRG1 to activate the Nrf2/HO-1 signaling. In summary, inhibiting miR-222-3p in IECs attenuates oxidative stress by targeting BRG1 to activate the Nrf2/HO-1 signaling, thereby reducing colonic inflammation and tumorigenesis.

Breast cancer (BC) is a common malignancy with highly female incidence. So far the function of notoginsenoside R1 (NGR1), the extract from Panax notoginseng, has not been clearly elucidated in BC. Optimal culture concentration and time of NGR1 were investigated by cell counting kit-8 assay. Cell proliferation ability was measured by colony formation assays. Transwell assay was used to detect the effect of NGR1 on cell migration and invasion. The apoptosis rate of cells between each group was measured by TUNEL assay. NGR1 treatment has an inhibitory effect on proliferation, migration, invasion, and angiogenesis and a stimulating effect on cell cycle arrest and apoptosis of Michigan Cancer Foundation-7 (MCF-7) cells. The 50% growth inhibitory concentration for MCF-7 cells at 24 h was 148.9 mmol/L. The proportions of MCF-7 cells arrested in the G0/G1 phase were 36.94±6.78%, 45.06±5.60%, and 59.46±5.60% in the control group, 75, and 150 mmol/L groups, respectively. Furthermore, we revealed that NGR1 treatment attenuates BC progression by targeted downregulating CCND2 and YBX3 genes. Additionally, YBX3 activates phosphatidylinositol 3-phosphate kinase (PI3K)/protein kinase B (Akt) signaling pathway by activating kirsten rat sarcoma viral oncogene, which is an activator of the PI3K/Akt signaling pathway. These results suggest that NGR1 can act as an efficacious drug candidate that targets the YBX3/PI3K/Akt axis in patients with BC.

Integrin subunit alpha V (ITGAV), a subunit of the integrin receptor, is involved in many types of cancers. In order to explore the potential mechanisms of ITGAV in cancers, we carried out a comprehensive pan-cancer analysis using public database. In this study, ITGAV expression in different cancers and the relationship between ITGAV and clinic-pathological features, prognosis, genetic alteration, epigenetic modification, and tumor immune microenvironment were systemically analyzed. Gene enrichment analysis was performed to explore potential functions of ITGAV in gastric cancer (GC). GC tissue microarrays and in vitro cell experiments were used to verify the prediction results in GC. The results revealed that ITGAV was variably expression in different cancers, and ITGAV had a certain prognostic and diagnostic value in most cancers, including GC. ITGAV expression was found to be related to genetic alteration, DNA methylation, immune checkpoint gene, and immune cell infiltration in multiple cancers. Functional analyses revealed that ITGAV was involved in the regulation of EMC remodeling, ferroptosis, and cuproptosis in GC. In vitro experiments verified that ITGAV was correlated with GC cell proliferation, apoptosis, migration, and invasion. Our study demonstrated that ITGAV can be used as an effective prognostic and immunological biomarker for multiple cancers. ITGAV can promote GC malignant progression and could serve as a potential therapeutic target for GC treatment.

Little is known about what roles the pregnane X receptor (PXR) and constitutive androstane receptor (CAR) play in drug metabolism in high-altitude hypoxia. Likewise, the potential interaction of nuclear receptors and drug metabolism enzymes during drug metabolism of high-altitude hypoxia is not fully understood. In this work, we investigated the effects of high-altitude hypoxia on transcriptional regulation of cytochrome P450 (CYP450) and UDP-glucuronosyltransferase 1A1 (UGT1A1) genes mediated by PXR and CAR proteins. The protein and mRNA expressions of CYP450, UGT1A1, PXR, and CAR were determined by enzyme-linked immunosorbent assay and qPCR in rats and HepG2 cell lines under hypoxia. Hypoxia potently inhibited the CYP450 isoforms, UGT1A1, PXR, and CAR protein and mRNA expression. To clarify whether PXR and CAR regulate various genes involved in drug metabolism of high-altitude hypoxia, we investigated the expression of CYP1A2, CYP2C9, CYP2E1, CYP3A4, and UGT1A1 using a dual-luciferase reporter assay after treatment with Ketoconazole (KCZ) and Retinoic acid (RA), or silenced PXR and CAR gene expression. In HepG2 cells, hypoxia, KCZ, and RA inhibited CYP450 isoforms and UGT1A1 expression. Activation of PXR and CAR in cells treated with 6-(4-chlorophenyl)-imidazo (2,1-b) thiazole-5-carbaldehyde (CITCO) and rifampicin (Rif) resulted in the enhancement of CYP450 isoforms, UGT1A1, PXR, and CAR. In contrast, this effect was not observed under hypoxia. Taken together, our results suggest that hypoxia inhibits CYP1A2, CYP2C9, CYP2E1, CYP3A4, and UGT1A1 expression via the PXR and CAR regulatory pathway.

AbstractObjectiveTo evaluate the diagnostic accuracy and safety of using magnetically guided capsule endoscopy with a detachable string (ds-MCE) for detecting and grading oesophagogastric varices in adults with cirrhosis.DesignProspective multicentre diagnostic accuracy study.Setting14 medical centres in China.Participants607 adults (>18 years) with cirrhosis recruited between 7 January 2021 and 25 August 2022. Participants underwent ds-MCE (index test), followed by oesophagogastroduodenoscopy (OGD, reference test) within 48 hours. The participants were divided into development and validation cohorts in a ratio of 2:1.Main outcome measuresThe primary outcomes were the sensitivity and specificity of ds-MCE in detecting oesophagogastric varices compared with OGD. Secondary outcomes included the sensitivity and specificity of ds-MCE for detecting high risk oesophageal varices and the diagnostic accuracy of ds-MCE for detecting high risk oesophagogastric varices, oesophageal varices, and gastric varices.Resultsds-MCE and OGD examinations were completed in 582 (95.9%) of the 607 participants. Using OGD as the reference standard, ds-MCE had a sensitivity of 97.5% (95% confidence interval 95.5% to 98.7%) and specificity of 97.8% (94.4% to 99.1%) for detecting oesophagogastric varices (both P<0.001 compared with a prespecified 85% threshold). When using the optimal 18% threshold for luminal circumference of the oesophagus derived from the development cohort (n=393), the sensitivity and specificity of ds-MCE for detecting high risk oesophageal varices in the validation cohort (n=189) were 95.8% (89.7% to 98.4%) and 94.7% (88.2% to 97.7%), respectively. The diagnostic accuracy of ds-MCE for detecting high risk oesophagogastric varices, oesophageal varices, and gastric varices was 96.3% (92.6% to 98.2%), 96.9% (95.2% to 98.0%), and 96.7% (95.0% to 97.9%), respectively. Two serious adverse events occurred with OGD but none with ds-MCE.ConclusionThe findings of this study suggest that ds-MCE is a highly accurate and safe diagnostic tool for detecting and grading oesophagogastric varices and is a promising alternative to OGD for screening and surveillance of oesophagogastric varices in patients with cirrhosis.Trial registrationClinicalTrials.gov NCT03748563.

Objectives To analyze the curative effect of TiRobot surgical robotic navigation and location system‐assisted percutaneous sacroiliac screw fixation and percutaneous sacroiliac screw by traditional fluoroscopy, and to summarize the safety and benefits of TiRobot. Methods A total of 91 patients with pelvic posterior ring fractures from December 2015 to February 2018 were included in this study. According to the surgical methods selected by the patients, the patients were divided into a TiRobot surgical robotic navigation and location system group (TiRobot group) and a percutaneous sacroiliac screw fixation group (traditional group). Statistical indicators included the number of sacroiliac screws, the time of planning the sacroiliac screw path, fluoroscopy frequency, fluoroscopy time, operation time, length of incision, blood loss, anesthesia time, the healing process of skin incisions, and fracture healing time. Fracture reduction was evaluated according to the maximum displacement degree at the inlet and outlet view X‐ray or CT. Matta standard was used to evaluate fracture reduction. At the last follow‐up, the Majeed function system was used to evaluate the function. Results All patients were followed up for 8 to 32 months. A total of 66 sacroiliac screws were implanted in the TiRobot group. A total of 43 sacroiliac screws were implanted in the traditional group. There were statistically significant differences in terms of fluoroscopy frequency, fluoroscopy time, operation time, incision length, anesthesia time, and blood loss between the two groups; the TiRobot group was superior to the traditional group. The healing time of the TiRobot group and the traditional group was 4.61 ± 0.68 months (range, 3.5–6.3 months) and 4.56 ± 0.78 months (range, 3.4–6.2 months), respectively, and there was no statistical difference. Postoperatively, by Matta standard, the overall excellent and good rate of fracture reduction was 89.28% and 88.57%, respectively. At the last follow‐up, by Majeed function score, the overall excellent and good rate was 91.07% and 91.43%. There was no statistical difference between the two groups. Conclusion Sacroiliac screw implantation assisted by TiRobot to treat the posterior pelvic ring fractures has the characteristics of less trauma, shorter operation time, and less blood loss. TiRobot has the characteristics of high safety and accuracy and has great clinical application value.