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To improve the interfacial bonding between hollow microspheres (RiM01) and natural rubber (NR), the silane coupling agents γ‐aminopropyltriethoxysilane (KH550) and γ‐methacryloyloxypropyltrimethoxysilane (KH570) are used in this study as intermediate reaction platforms for the modification of (RiM01) with glycidyl methacrylate (GMA), respectively. In the process, GMA reacts with KH550 and KH570 through epoxy group ring‐opening and free radical polymerization, respectively. Different NR/RiM01@GMA composites are prepared by a mechanical blending method. The results show that the addition of GMA improves the interfacial bonding between RiM01 and NR, and enhances the vulcanization rate and cross‐linking degree of the rubber composites. When KH550 is used as the reaction platform, the tensile strength of the rubber composites increases by 24% compared to composites with unmodified RiM01, while when KH570 is used, the tensile strength increases by 18%. Additionally, the tear strength and abrasion resistance of the rubber composites increase by 13% and 15%, respectively, when KH570 is used as the reaction platform. At the same time, the filler‐matrix interaction is strongest when KH570 is used as the reaction platform, and the rubber composites exhibit the lowest rolling resistance and the best resistance to heat and oxygen aging. Highlight: Modification of hollow microspheres by grafting GMA with KH550 and KH570, respectively.Improvement of rubber composite properties after modificationGMA improves the interfacial bonding between hollow microspheres and rubber. [ABSTRACT FROM AUTHOR]

The diterpene synthase AfAS was identified from Aspergillus fumigatiaffinis. Its amino acid sequence and—according to a structural model—active site architecture are highly similar to those of the fusicocca‐2,10(14)‐diene synthase PaFS, but AfAS produces a structurally much more complex diterpene with a novel 6–5–5–5 tetracyclic skeleton called asperfumene. The cyclisation mechanism of AfAS was elucidated through isotopic labelling experiments and DFT calculations. The reaction cascade proceeds in its initial steps through similar intermediates as for the PaFS cascade, but then diverges through an unusual vicinal deprotonation‐reprotonation process that triggers a skeletal rearrangement at the entrance to the steps leading to the unique asperfumene skeleton. The structural model revealed only one major difference between the active sites: The PaFS residue F65 is substituted by I65 in AfAS. Intriguingly, site‐directed mutagenesis experiments with both diterpene synthases revealed that position 65 serves as a bidirectional functional switch for the biosynthesis of tetracyclic asperfumene versus structurally less complex diterpenes. [ABSTRACT FROM AUTHOR]

Eukaryotic cells possess multiple mechanisms of self‐destruction, including pyroptosis and necroptosis. Pyroptosis is a type of programmed cell death characterized by cellular rupture and linked to inflammation. SnoRNA, a small non‐coding RNA in the nucleolus, can dysregulate specific RNAs through 2'‐O‐methylation, contributing to tumorigenesis. Our StarBase and qRT‐PCR analysis revealed SNORD99 upregulation in endometrial cancer (EC) tissue compared to normal tissue, suggesting its role in pathogenesis. SNORD99 overexpression enhanced migration and proliferation of EC cells, while ASO‐mediated suppression reduced malignant cell spread and division. RNA‐seq and base‐comparing analysis identified GSDMD's differential expression upon SNORD99 overexpression, forming the SNORD99‐FBL RNP complex. RTL‐P experiments showed SNORD99 increased GSDMD's 2'‐O‐methylation. SNORD99 reduced GSDMD, caspase‐1, and NLRP3 protein levels, implicating its role in pyroptosis. Optical and electron microscopy confirmed enhanced pyroptosis features. In summary, SNORD99 modifies GSDMD via 2'‐O‐methylation, suppressing pyroptosis and promoting EC progression. Developing pyroptosis‐inducing drugs may offer new cancer treatment avenues. [ABSTRACT FROM AUTHOR]

The development of a methodology for synthesizing value‐added urea (CO(NH2)2) via a renewable electricity‐driven C−N coupling reaction under mild conditions is highly anticipated. However, the complex catalytic active sites that act on the carbon and nitrogen species make the reaction mechanism unclear, resulting in a low efficiency of C−N coupling from the co‐reduction of carbon dioxide (CO2) and nitrate (NO3−). Herein, we propose a novel tandem catalyst of Mo‐PCN‐222(Co), in which the Mo sites serve to facilitate nitrate reduction to the *NH2 intermediate, while the Co sites enhance CO2 reduction to carbonic oxide (CO), thus synergistically promoting C−N coupling. The synthesized Mo‐PCN‐222(Co) catalyst exhibited a noteworthy urea yield rate of 844.11 mg h−1 g−1, alongside a corresponding Faradaic efficiency of 33.90 % at −0.4 V vs. reversible hydrogen electrode (RHE). By combining in situ spectroscopic techniques with density functional theory calculations, we demonstrate that efficient C−N coupling is attributed to a tandem system in which the *NH2 and *CO intermediates produced by the Mo and Co active sites of Mo‐PCN‐222(Co) stabilize the formation of the *CONH2 intermediate. This study provides an effective avenue for the design and synthesis of tandem catalysts for electrocatalytic urea synthesis. [ABSTRACT FROM AUTHOR]

Background and Aim: Patients with cholelithiasis (CL) or cholecystectomy (CE) would have more chances of getting colorectal adenoma (CRA) or cancer (CRC). We aimed to figure out the effects of gut microbiota and bile acid on colorectal neoplasm in CL and CE patients. Methods: This was a retrospective observational study that recruited 514 volunteers, including 199 people with normal gallbladders (normal), 152 CL, and 163 CE patients. Discovery cohort was established to explore the difference in gut microbiota through 16S rRNA and metagenomics sequencing. Validation cohort aimed to verify the results through quantitative polymerase chain reaction (qPCR). Results: Significant enrichment of Escherichia coli was found in patients with cholelithiasis or cholecystectomy both in the discovery cohort (16S rRNA sequencing, PNormal‐CL = 0.013, PNormal‐CE = 0.042; metagenomics sequencing, PNormal‐CE = 0.026) and validation cohort (PNormal‐CL < 0.0001, PNormal‐CE < 0.0001). Pks+E. coli was found enriched in CL and CE patients through qPCR (in discovery cohort: PNormal‐CE = 0.018; in validation cohort: PNormal‐CL < 0.0001, PNormal‐CE < 0.0001). The differences in bile acid metabolism were found both through Tax4Fun analysis of 16S rRNA sequencing (Ko00120, primary bile acid biosynthesis, PNormal‐CE = 0.014; Ko00121, secondary bile acid biosynthesis, PNormal‐CE = 0.010) and through metagenomics sequencing (map 00121, PNormal‐CE = 0.026). The elevation of serum total bile acid of CE patients was also found in validation cohort (PNormal‐CE < 0.0001). The level of serum total bile acid was associated with the relative abundance of pks+E. coli (r = 0.1895, P = 0.0012). Conclusions: E. coli, especially pks+ species, was enriched in CL and CE patients. Pks+E. coli and bile acid metabolism were found associated with CRA and CRC in people after cholecystectomy. [ABSTRACT FROM AUTHOR]

Background and Aim: Cohort studies have linked metabolic syndrome (MetS) to gastrointestinal (GI) cancer risk. We aimed to evaluate the associations between MetS, its components, and combinations of MetS components with eight GI cancers risk. Methods: We conducted a systematic search of prospective cohort studies and performed a meta‐analysis. Subgroup analyses regarding diagnostic criteria, sex, cancer sites, histological subtypes, ethnic groups, and studies adjusted for alcohol consumption were carried out. Mendelian randomization (MR) was employed to evaluate the causality between 17 MetS‐related traits and eight GI cancers among Europeans and Asians separately. Results: Meta‐analyses of 31 prospective studies indicated that MetS was significantly associated with an increased risk of colorectal cancer (CRC) (RR [95% CI] = 1.13 [1.12–1.15]), esophageal cancer (EC) (RR [95% CI] = 1.17 [1.03–1.32]), gallbladder cancer (GBC) (RR [95% CI] = 1.37[1.10–1.71]), liver cancer (LC) (RR [95% CI] = 1.46 [1.29–1.64]), and pancreatic cancer (PaC) (RR [95% CI] = 1.25 [1.20–1.30]), but not gastric cancer (GC) (RR [95% CI] = 1.11 [0.96–1.28]). Regarding the associations between MetS components and GI cancers risk, the following associations showed statistical significance: obesity‐CRC/LC/EC/, hypertriglyceridemia‐LC/PaC, reduced high‐density lipoprotein (HDL)‐CRC/LC/GC/PaC, hyperglycemia‐CRC/LC/PaC, and hypertension‐CRC/LC/EC/PaC. Sex‐specific associations were observed between individual MetS components on GI cancers risk. Among the top three common combinations in both sexes, obesity + HTN + hyperglycemia had the strongest association with CRC risk (RR [95% CI] = 1.54 [1.49–1.61] for males and 1.27 [1.21–1.33] for females). MR analyses revealed causality in 16 exposure–outcome pairs: waist‐to‐hip ratio/BMI/HbA1c‐CRC; BMI/childhood obesity/waist circumference/T2DM/glucose‐EC; BMI/waist circumference/cholesterol‐LC; cholesterol/childhood obesity/waist circumference/HbA1c‐PaC; and HbA1c‐GBC. These results were robust against sensitivity analyses. Conclusions: Since MetS is reversible, lifestyle changes or medical interventions targeting MetS patients might be potential prevention strategies for GI cancers. [ABSTRACT FROM AUTHOR]

Background: Recent clinical trials have evaluated the efficacy of vonoprazan‐amoxicillin (VA) dual therapy as the first‐line treatment for Helicobacter pylori infection in different regions with inconsistent results reported. In this systematic review and meta‐analysis, we aimed to evaluate the efficacy of VA dual therapy compared to the currently recommended therapy for eradicating H. pylori. Materials and Methods: A comprehensive search of the PubMed, Cochrane, and Embase databases was performed using the following search terms: ("Helicobacter" OR "H. pylori" OR "Hp") AND ("vonoprazan" OR "potassium‐competitive acid blocker" OR "P‐CAB") AND ("amoxicillin" OR "penicillin") AND ("dual"). The primary outcome was to evaluate the eradication rate according to intention‐to‐treat and per‐protocol analysis. The secondary outcomes were adverse events and compliance. Results: A total of 15 studies involving 4, 568 patients were included. The pooled eradication rate of VA dual therapy was 85.0% and 90.0% by intention‐to‐treat and per‐protocol analysis, respectively. The adverse events rate and compliance of VA dual therapy were 17.5% and 96%, respectively. The efficacy of VA dual therapy was superior to proton pump inhibitors‐based triple therapy (82.0% vs. 71.4%, p < 0.01) but lower than vonoprazan‐containing quadruple therapy (83.1% vs. 93.3%, p = 0.02). 7‐day VA dual therapy showed lower eradication rates than 10‐day (χ2 = 24.09, p < 0.01) and 14‐day VA dual therapy (χ2 = 11.87, p < 0.01). The adverse events rate of VA dual therapy was lower than vonoprazan triple therapy (24.6% vs. 30.9%, p = 0.01) and bismuth‐containing quadruple therapy (20.5% vs. 47.9%, p < 0.01). No significant difference of compliance was observed between VA dual therapy and each subgroup. Conclusion: VA dual therapy, a novel regimen, showed high efficacy as the first‐line treatment for H. pylori eradication, which should be optimized before application in different regions. [ABSTRACT FROM AUTHOR]

Accidental collisions from overheight vehicles often result in significant damage of bridges. To ensure the safety of the bridge structure, it is essential to develop a method to evaluate the damage caused by these impact loadings. This study aims to investigate the damage mechanism of a prestressed concrete (PC) box girder bridge subjected to overheight vehicle impact using the finite element analysis method. Parametric analyses were performed to study the effects of various factors on the impact force and deformation performance of the bridge. In addition, a damage assessment formula, based on the vertical residual bearing capacity, is proposed to evaluate the damage state of the impacted PC box girder. A mass–velocity (m–v) curve is developed to characterize the damage levels of the impacted PC girder under different vehicle velocity and mass conditions. Then, a theoretical equation for predicting the maximum impact force during the vehicle‐bridge collision is developed. The numerical analysis results show that vehicle‐related parameters have a significant influence on both impact force and local damage of the PC box girder bridge. The proposed mass–velocity (m–v) curve can be used to evaluate the damage state of the PC box girder by relating the performance levels of the girder to each damage index. Moreover, the predicted maximum impact force can be used as an important index to assess the extent of the local damage of the PC box girder. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) incidence has increased among patients aged <50 years. Exploring high‐risk factors and screening high‐risk populations may help lower early‐onset CRC (EO‐CRC) incidence. We developed noninvasive predictive models for EO‐CRC and investigated its risk factors. Methods: This retrospective multicenter study collected information on 1756 patients (811 patients with EO‐CRC and 945 healthy controls) from two medical centers in China. Sociodemographic features, clinical symptoms, medical and family history, lifestyle, and dietary factors were measured. Patients from one cohort were randomly assigned (8:2) to two groups for model establishment and internal validation, and another independent cohort was used for external validation. Multivariable logistic regression, random forest, and eXtreme Gradient Boosting (XGBoost) were performed to establish noninvasive predictive models for EO‐CRC. Some variables in the model influenced EO‐CRC occurrence and were further analyzed. Multivariable logistic regression analysis yielded adjusted odd ratios (ORs) and 95% confidence intervals (CIs). Results: All three models showed good performance, with areas under the receiver operator characteristic curves (AUCs) of 0.82, 0.84, and 0.82 in the internal and 0.78, 0.79, and 0.78 in the external validation cohorts, respectively. Consumption of sweet (OR 2.70, 95% CI 1.89–3.86, P < 0.001) and fried (OR 2.16, 95% CI 1.29–3.62, P < 0.001) foods ≥3 times per week was significantly associated with EO‐CRC occurrence. Conclusion: We established noninvasive predictive models for EO‐CRC and identified multiple nongenetic risk factors, especially sweet and fried foods. The model has good performance and can help predict the occurrence of EO‐CRC in the Chinese population. [ABSTRACT FROM AUTHOR]

Two novel silver(I) phenanthroline derivative complexes (P‐235 and P‐239) have been synthesized and characterized by IR, HPLC‐MS, and 1HNMR. The cytotoxicity of two complexes exhibited significant cytotoxicity against human breast cancer (MDA‐MB‐231) cell line (IC50 = 0.48 ± 0.01 and 0.12 ± 0.01 μM) and less toxicity than cisplatin by MTT assays. Furthermore, anticancer mechanistic studies showed that P‐235 and P‐239 induced G2/M phase cell cycle arrest to inhibit the growth of MDA‐MB‐231 cells. Flow cytometry analysis showed that MDA‐MB‐231 cells could be significantly induced to undergo apoptosis by P‐235 and P‐239. And P‐235‐ and P‐239‐induced apoptosis was linked with reactive oxygen species (ROS) production. Further study revealed that P‐235 and P‐239 cause mitochondrial membrane potential depolarization and destroy mitochondrial membrane potential. [ABSTRACT FROM AUTHOR]

The novel HLA‐C*15:279 allele differs from HLA‐C*15:02:01:01 by five nucleotide substitutions in exons 4 and 5. [ABSTRACT FROM AUTHOR]

Introduction: A high incidence of mortality and severe COVID‐19 infection was reported in hematopoietic stem cell transplant (HSCT) recipients during the early phases of the COVID‐19 pandemic; however, outcomes with subsequent severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) variants, such as the omicron variant, have yet to be reported. Additionally, rollout of COVID‐19 vaccinations in subsequent pandemic waves may modify COVID‐19 disease severity and mortality in this immunocompromised population. We describe COVID‐19 outcomes among a highly vaccinated population of HSCT recipients at a single center during successive waves of community transmission arising from the SARS‐CoV‐2 delta and omicron variants. Methods: We retrospectively reviewed medical records of all HSCT recipients at our institution who tested positive for SARS‐CoV‐2 from May 2021 to May 2022. Descriptive statistics were reported; the chi‐square test was utilized to identify factors associated with 90‐day all‐cause mortality and severity of COVID‐19 infection. Results: Over the 1‐year study period, 77 HSCT recipients at our center contracted COVID‐19 (43 allogenic; 34 autologous). Twenty‐six (33.8%) patients were infected with the SARS‐CoV‐2 delta variant, while 51 (66.2%) had the SARS‐CoV‐2 omicron variant. Thirty‐nine (50.6%) patients required hospitalization. More than 80% had received prior COVID‐19 vaccination (57.1% with two doses, 27.3% with three doses). The majority (90.9%) had mild disease; only one (1.3%) patient required mechanical ventilation. Active hematological disease at time of COVID‐19 infection was associated with increased odds of mortality [odds ratio (OR) = 6.90, 95% confidence interval (CI) = 1.20–40]. The 90‐day all‐cause mortality was 7.8% (six patients). Infection with the omicron variant (vs. delta) was associated with less severe illness (OR = 0.05, 95% CI = 0.01–0.47) and decreased odds of mortality (OR = 0.08, 95% CI = 0.01–0.76). Being on immunosuppression (OR = 5.10, 95% CI = 1.10–23.60) and being unvaccinated at disease onset (OR = 14.76, 95% CI = 2.89–75.4) were associated with greater severity of COVID‐19 infection. Conclusion: We observed favorable outcomes with COVID‐19 infection in a cohort of vaccinated HSCT patients. The SARS‐CoV‐2 omicron variant was associated with both less severe illness and decreased odds of mortality. As COVID‐19 moves toward endemicity, early access to treatment and encouraging vaccination uptake is crucial in mitigating the challenge of COVID‐19 management among HSCT recipients. Surveillance and assessment of clinical outcomes with new SARS‐CoV‐2 variants also remains important in this immunocompromised population. [ABSTRACT FROM AUTHOR]

The frequency of p53 mutations in colorectal cancer (CRC) is approximately 40–50%. A variety of therapies are being developed to target tumors expressing mutant p53. However, potential therapeutic targets for CRC expressing wild‐type p53 are rare. In this study, we show that METTL14 is transcriptionally activated by wild‐type p53 and suppresses tumor growth only in p53‐wild‐type (p53‐WT) CRC cells. METTL14 deletion promotes both AOM/DSS and AOM‐induced CRC growth in mouse models with the intestinal epithelial cell‐specific knockout of METTL14. Additionally, METTL14 restrains aerobic glycolysis in p53‐WT CRC, by repressing SLC2A3 and PGAM1 expression via selectively promoting m6A‐YTHDF2‐dependent pri‐miR‐6769b/pri‐miR‐499a processing. Biosynthetic mature miR‐6769b‐3p and miR‐499a‐3p decrease SLC2A3 and PGAM1 levels, respectively, and suppress malignant phenotypes. Clinically, METTL14 only acts as a beneficial prognosis factor for the overall survival of p53‐WT CRC patients. These results uncover a new mechanism for METTL14 inactivation in tumors and, most importantly, reveal that the activation of METTL14 is a critical mechanism for p53‐dependent cancer growth inhibition, which could be targeted for therapy in p53‐WT CRC. Synopsis: METTL14 specifically counteracts colorectal tumorigenesis in p53‐wild‐type cells by attenuating aerobic glycolysis. METTL14 decreases SLC2A3 and PGAM1 expression via selectively promoting m6A‐YTHDF2‐dependent pri‐miR‐6769b and pri‐miR‐499a processing. METTL14 is transcriptionally activated by wild‐type p53 and inhibits progression of p53‐wild‐type colorectal cancer (CRC).METTL14‐mediated m6A modification promotes YTHDF2‐dependent processing of pri‐miR‐6769b and pri‐miR‐499a.miR‐499a‐3p and miR‐6769b‐3p target SLC2A3 and PGAM1, respectively, thereby inhibiting glycolysis in p53‐wild‐type CRC.METTL14 expression inversely correlates with poor prognosis in p53‐wild‐type colorectal cancer. [ABSTRACT FROM AUTHOR]

Aim: To investigate the gender and socioeconomic disparities in the global burden of chronic kidney disease (CKD) due to glomerulonephritis from 1990 to 2019. Methods: Data were extracted from the global burden of diseases (GBD) 2019 study, including incidence, prevalence and disability‐adjusted life‐years (DALYs). Estimated annual percentage changes (EAPCs) were calculated to quantify the temporal trends in age‐standardized rate (ASR) of CKD due to glomerulonephritis. Paired t‐test, paired Wilcoxon signed‐rank test and Spearman correlation were performed to analyse the association and gender disparity in CKD due to glomerulonephritis. Results: Globally, incident cases of CKD due to glomerulonephritis increased 81% from 9 557 397 in 1990 to 17 308 071 in 2019. The age‐standardized incidence rate increased by 1.47 compared with 1990 and DALYs increased by 1.35 compared with 1990 (per 100 000). The number of patients with CKD due to glomerulonephritis in low‐middle SDI (3829917) and middle SDI (6268817) regions accounts for more than 55% of the total cases. CKD due to glomerulonephritis caused a higher burden including the incidence rate (p <.0001) and DALY rate (p <.0001) in men compared to women. The age‐standardized DALY rate was negatively correlated with SDI (ρ = −0.64, p <.001). In the analysis of risk factors for DALYs, male individuals had a larger burden of hypertension, high BMI and high sodium diet in the DALY rates than female subjects. Conclusion: The burden of CKD due to glomerulonephritis was more skewed towards developing and less developed economies and differed by gender, so certain nations should implement far more focused and targeted policies. Summary at a Glance: We examined the gender and socioeconomic disparities in the burden of chronic kidney disease (CKD) due to glomerulonephritis. A higher burden, including the incidence and DALY rate, was observed in men compared to women. The burden of CKD due to glomerulonephritis was more skewed towards developing and less developed economies. [ABSTRACT FROM AUTHOR]

Background and Aim: Appendectomy is associated with various diseases, but whether it increases the risk of colorectal cancer (CRC) remains uncertain. We conducted a systematic review and meta‐analysis aimed at investigating the suggested correlation between appendectomy and CRC. Methods: Systematic retrieval was performed using the PubMed, Embase, Cochrane library, Web of Science, and ClinicalTrials.gov databases up to May 4, 2022, for studies reported the influence of appendectomy on CRC, colon cancer (CC) or rectal cancer (RC). Odd ratios (ORs) and 95% confidence intervals (CIs) of CRC after appendectomy were pooled using the random effects model. Subgroup analyses were carried on by region, sex, and tumor location. Results: Our search identified 1743 articles, of which 22 studies from three continents published between 1964 and 2022 were eligible for inclusion. Overall, people with appendectomy had a higher risk of CRC (OR = 1.31; 95% CI [1.05, 1.62]). But the risk for Europeans was not significant (OR = 0.94; 95% CI [0.87, 1.02]; I2 = 0%), while for Americans and Asians, appendectomy would increase the risk of CRC (OR = 1.68; 95% CI [1.15, 2.44]; I2 = 65% and OR = 1.46; 95% CI [1.04, 2.05]; I2 = 98%), especially in females and in developing countries. It is worth noting that appendectomy might be a protective factor for CC in European women (OR = 0.87; 95% CI [0.77, 0.98]; I2 = 0%). Conclusions: Appendectomy may be a risk factor for CRC, with varying degrees in different populations. More high‐quality cross‐regional studies are needed for better clinical decision making. [ABSTRACT FROM AUTHOR]

Purpose: Determination of reliable change of radiomics feature over time is essential and vital in delta-radiomics, but has not yet been rigorously examined. This study attempts to propose a methodological approach using reliable change index (RCI), a statistical metric to determine the reliability of quantitative biomarker changes by accounting for the baseline measurement standard error, in delta-radiomics. The use of RCI was demonstrated with the MRI data acquired from a group of prostate cancer (PCa) patients treated by 1.5 T MRI-guided radiotherapy (MRgRT). Methods: Fifty consecutive PCa patients who underwent five-fractionated MRgRT were retrospectively included, and 1023 radiomics features were extracted from the clinical target volume (CTV) and planning target volume (PTV). The two MRI datasets acquired at the first fraction (MRI11 and MRI21) were used to calculate the baseline feature reliability against image acquisition using intraclass correlation coefficient (ICC). The RCI was constructed based on the baseline feature measurement standard deviation, ICC, and feature value differences at two time points between the fifth (MRI51) and the first fraction MRI (MRI11). The reliable change of features was determined in each patient only if the calculated RCI was over 1.96 or smaller than -1.96. The feature changes between MRI51 and MRI11 were correlated to two patient-reported quality-of -life clinical endpoints of urinary domain summary score (UDSS) and bowel domain summary score (BDSS) in 35 patients using the Spearman correlation test. Only the significant correlations between a feature that was reliably changed in =7 patients (20%) by RCI and an endpoint were considered as true significant correlations. Results: The 352 (34.4%) and 386 (37.7%) features among all 1023 features were determined by RCI to be reliably changed in more than five (10%) patients in the CTV and PTV, respectively. Nineteen features were found reliably changed in the CTV and 31 features in the PTV, respectively, in 10 (20%) or more patients. These features were not necessarily associated with significantly different longitudinal feature values (group p-value < 0.05). Most reliably changed features in more than 10 patients had excellent or good baseline test-retest reliability ICC, while none showed poor reliability. The RCI method ruled out the features to be reliably changed when substantial feature measurement bias was presented. After applying the RCI criterion, only four and five true significant correlations were confirmed with UDSS and BDSS in the CTV, respectively, with low true significance correlation rates of 10.8% (4/37) and 17.9% (5/28). No true significant correlations were found in the PTV. Conclusions: The RCI method was proposed for delta-radiomics and demonstrated using PCa MRgRT data. The RCI has advantages over some other statistical metrics commonly used in the previous delta-radiomics studies, and is useful to reliably identify the longitudinal radiomics feature change on an individual basis. This proposed RCI method should be helpful for the development of essential feature selection methodology in delta-radiomics. [ABSTRACT FROM AUTHOR]

Organic ultralong room‐temperature phosphorescence (RTP) materials have attracted great attention for their wide applications in optoelectronic devices and bioimaging. However, the development of these materials remains a challenging task, partially due to the lack of rational molecular design strategies and unclear luminescence mechanisms. Herein, we present a method for facile access to structurally diverse substituted 1‐aminoisoquinoline derivatives through a copper‐catalyzed one‐pot three‐component coupling reaction that provides a promising approach to rapidly assemble a library of 1‐aminoisoquinolines for exploring the regularity of the host‐guest doped system. A series of host‐guest RTP materials with wide‐ranging lifetimes from 4.4 to 299.3 ms were constructed by doping various substituted isoquinolines derivatives into benzophenone (BP). Furthermore, 4 r/BP nanoparticles could be used for in‐vivo imaging with a signal‐to‐noise ratio value as high as 32, revealing the potential of the isoquinoline framework for the construction of high‐performance RTP materials. [ABSTRACT FROM AUTHOR]

Lacking a clear understanding of the molecular mechanism determining cancer cell sensitivity to oxidative phosphorylation (OXPHOS) inhibition limits the development of OXPHOS‐targeting cancer treatment. Here, cancer cell lines sensitive or resistant to OXPHOS inhibition are identified by screening. OXPHOS inhibition‐sensitive cancer cells possess increased OXPHOS activity and silenced nicotinamide N‐methyltransferase (NNMT) expression. NNMT expression negatively correlates with OXPHOS inhibition sensitivity and functionally downregulates the intracellular levels of S‐adenosyl methionine (SAM). Expression of DNA methyltransferase 1 (DNMT1), a SAM consumer, positively correlates with OXPHOS inhibition sensitivity. NNMT overexpression and DNMT1 inhibition render OXPHOS inhibition‐sensitive cancer cells resistant. Importantly, treatments of OXPHOS inhibitors (Gboxin and Berberine) hamper the growth of mouse tumor xenografts by OXPHOS inhibition sensitive but not resistant cancer cells. What's more, the retrospective study of 62 tumor samples from a clinical trial demonstrates that administration of Berberine reduces the tumor recurrence rate of NNMTlow/DNMT1high but not NNMThigh/DNMT1low colorectal adenomas (CRAs). These results thus reveal a critical role of the NNMT‐DNMT1 axis in determining cancer cell reliance on mitochondrial OXPHOS and suggest that NNMT and DNMT1 are faithful biomarkers for OXPHOS‐targeting cancer therapies. [ABSTRACT FROM AUTHOR]

Renal cell carcinoma is the most common malignant tumor of the kidneys and constitutes about 90% of all renal malignancies.[1] Renal cell carcinoma has an abundant blood supply and is thought to spread by lymphatic, hematogenous, and transcoelomic metastasis, or through direct invasion. Renal cell carcinoma is mostly diagnosed at an advanced stage, with a median survival time of only 6-12 months.[3] Gastric metastasis of renal cell carcinoma is extremely rare. A metastatic clear cell adenocarcinoma of renal origin was considered, which showed the same cellular subtype as her previous clear cell renal cell carcinoma (Figure 3). [Extracted from the article]

Herein, we report a cobalt‐catalyzed hydroarylation of maleimides followed by an annulation sequence for the synthesis of polycyclic azaheterocycles in one pot. The reaction proceeds under redox‐neutral conditions and is compatible with various functional groups. Notably, the as‐prepared product exhibits potential photophysical properties. [ABSTRACT FROM AUTHOR]

Objective: To clarify the endoscopic, clinicopathological, and growth characteristics of minute gastric cancer (MGC) and to improve its detection rate. Methods: Patients with early gastric cancer who underwent endoscopic submucosal dissection from July 2012 to September 2021 were retrospectively reviewed. MGC was defined as gastric cancer of 5 mm or less in size. Preoperative and postoperative endoscopic and pathological data were collected and analyzed. Follow‐up information was collected until 9 April 2022. Results: Eighty patients were enrolled, with 82 lesions observed under endoscopy and 87 diagnosed histopathologically. All patients received en bloc and curative resection. Compared with the time point when the last endoscopic examiniation prior to lesion deteciton was performed (t0), 64.29% of patients with MGC had disease progression at lesion detection (t1). However, 21.43% showed normal or only atrophic changes under white‐light endoscopy, and their lesions were diagnosed accidentally by random biopsy. The majority of MGC lesions presented as type IIc and reddish, and 95.00% of cases had well‐differentiated tubular adenocarcinoma. The mean growth rate of MGC was 0.0071 mm/day, and it took an average of 3.42 years to grow to 5 mm. There was no significant difference in the depth of invasion between the low cellular atypia group and the high cellular atypia group. Conclusions: Type IIc and reddish appearance are main endoscopic features of MGC. For cases with no obvious endoscopic changes, multipoint biopsy is helpful. MGC is mostly well differentiated and grows relatively slowly; therefore, MGC can still have a chance to be identified and resected curatively if it is missed diagnosed. [ABSTRACT FROM AUTHOR]

Inhibition of sodium-glucose cotransporter-2 (SGLT2) has been shown to be a safe and efficacious approach to support managing Type 2 diabetes. In the 2-year carcinogenicity study with the SGLT2 inhibitor empagliflozin in CD-1 mice, an increased incidence of renal tubular adenomas and carcinomas was identified in the male high-dose group but was not observed in female mice. An integrated review of available nonclinical data was conducted to establish a mode-of-action hypothesis for male mouse-specific tumorigenesis. Five key events were identified through systematic analysis to form the proposed mode-of-action: (1) Background kidney pathology in CD-1 mice sensitizes the strain to (2) pharmacology-related diuretic effects associated with SGLT2 inhibition. (3) In male mice, metabolic demand increases with the formation of a sex- and species-specific empagliflozin metabolite. These features converge to (4) deplete oxidative stress handling reserve, driving (5) constitutive cellular proliferation in male CD-1 mice. The proposed mode of action requires all five key events for empagliflozin to present a carcinogenicity risk in the CD-1 mouse. Considering that empagliflozin is not genotoxic in the standard battery of genotoxicity tests, and not all five key events are present in the context of female mice, rats, or humans, nor for other osmotic diuretics or other SGLT2 inhibitors, the observed male mouse renal tumors are not considered relevant to humans. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Recently, molecular ferroelectrics have attracted more and more attention due to their structural diversity, low cost of manufacture, and environmental‐friendly processing. However, most of the design strategies for molecular ferroelectrics have focused on the selection and modification of cations, and the use of anions has been rarely reported. Here, introducing distorted [CuBr4]2– tetrahedra, we obtained a high curie temperature (Tc) ferroelectric, [cyclopentylammonium]2CuBr4, with a Tc as high as 393 K, and exceeding commercial and most of reported molecular ferroelectric BaTiO3 (393 K). Variable‐temperature hysteresis loop shows the nonlinear P‐E loop of the crystal under a wide temperature range. Variable‐temperature single‐crystal X‐ray diffraction revealed that the Aizu expression can be written as mmmFmm2. In short, this work will inspire more creative strategies by exploiting the tunability of the anion module. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Recently, molecular ferroelectrics have attracted more and more attention due to their structural diversity, low cost of manufacture, and environmental‐friendly processing. However, most of the design strategies for molecular ferroelectrics have focused on the selection and modification of cations, and the use of anions has been rarely reported. Here, introducing distorted [CuBr4]2– tetrahedra, we obtained a high curie temperature (Tc) ferroelectric, [cyclopentylammonium]2CuBr4, with a Tc as high as 393 K, and exceeding commercial and most of reported molecular ferroelectric BaTiO3 (393 K). Variable‐temperature hysteresis loop shows the nonlinear P‐E loop of the crystal under a wide temperature range. Variable‐temperature single‐crystal X‐ray diffraction revealed that the Aizu expression can be written as mmmFmm2. In short, this work will inspire more creative strategies by exploiting the tunability of the anion module. [ABSTRACT FROM AUTHOR]

The wear resistance of rubber composite materials has always been the focus of research. The wear resistance will not only affect the service life of products and the safety of equipment, but also have an important impact on the environment. In this work, the preparation and properties of wear‐resistant rubber nanocomposites based on natural rubber (NR) were studied. It is dedicated to improving the wear resistance of NR composites. On this basis, the dispersibility of montmorillonite (MMT) hybrid materials in NR‐based rubber composites was explored. SiO2@MMT, SiO2@MMT@KH560, PDA@GO, and MMT@GO hybrid materials were prepared, and the hybrid materials were applied to the NR/butadiene rubber (NR/BR) system, and NR/BR/hybrid material composite materials were successfully prepared. The results show that the interlayer spacing of MMT in hybrid materials increases, which effectively improves the dispersibility of MMT in rubber matrix. The tensile strength of NR/BR/MMT@GO composite material increased by 12%, the elongation at break increased by 25%, the DIN abrasion decreased by 16.5% compared with the optimum wear rubber formula, and the wear resistance was greatly improved. This work provides a feasible way for the design of functional polymer composites. [ABSTRACT FROM AUTHOR]

The wet skid resistance and thermal conductivity of "green tire" are the focus of research. In this work, through the use of different types of silane coupling agents, the surface of SiO2 and graphene oxide (GO) were grafted with amino and epoxy groups, respectively. The in‐situ generated SiO2 was grafted to the surface of GO by ring‐opening reaction of amino and epoxy groups. The emulsion styrene butadiene rubber/natural rubber latex (ESBR/NRL) composites were prepared by gas assisted spray flocculation process to improve the dispersion performance of hybrid filler. Because the surface of the hybrid filler contains amino and epoxy groups, it can be added as a reactive compatibilizer into the ESBR/NRL composites to improve the interface compatibility and synergistic reinforcement effect. Compared with the composites filled with SiO2, the composites filled with hybrid filler have excellent wet skid resistance and mechanical properties. When the mass ratio of GO to SiO2 is 3:10, the mechanical properties and wet skid resistance of rubber composites increase by 96.7% and 20.6%, respectively. Our preparation method of hybrid filler and flocculation process of rubber composites have broad application prospects in "green tire." [ABSTRACT FROM AUTHOR]

The outer mitochondrial membrane protein mitoNEET (mNT) is a recently identified iron‐sulfur protein containing a unique Fe2S2(His)1(Cys)3 metal cluster with a single Fe−N(His87) coordinating bond. This labile Fe−N bond led to multiple unfolding/rupture pathways of mNT and its cluster by atomic force microscopy‐based single‐molecule force spectroscopy (AFM‐SMFS), one of most common tools for characterizing the molecular mechanics. Although previous ensemble studies showed that this labile Fe−N(His) bond is essential for protein function, they also indicated that the protein and its [2Fe2S] cluster are stable under acidic conditions. Thus, we applied AFM‐SMFS to measure the stability of mNT and its cluster at pH values of 6, 7, and 8. Indeed, all previous multiple unfolding pathways of mNT were still observed. Moreover, single‐molecule measurements revealed that the stabilities of the protein and the [2Fe2S] cluster are consistent at these pH values with only ≈20 pN force differences. Thus, we found that the behavior of the protein is consistent in both weakly acidic and basic solutions despite a labile Fe−N bond. [ABSTRACT FROM AUTHOR]

Objective: Analyze the clinical and genetic characteristics of a rare Chinese family with Multiple synostoses syndrome and identify the causative variant with the high‐throughput sequencing approach. Methods: The medical history investigation, physical examination, imaging examination, and audiological examination of the family members were performed. DNA samples were extracted from the family members. The candidate variant was identified by performing whole‐exome sequencing of the proband, then verified by Sanger sequencing in the family. Results: The family named HBSY‐018 from Hubei province had 18 subjects in three generations, and six subjects were diagnosed with conductive or mixed hearing loss. Meanwhile, characteristic features including short philtrum, hemicylindrical nose, and hypoplastic alae nasi were noticed among those patients. Symptoms of proximal interdigital joint adhesion and inflexibility were found. The family was diagnosed as Multiple synostoses syndrome type 1 (SYNS1).The inheritance pattern of this family was autosomal dominant. A novel mutation in the NOG gene c.533G>A was identified by performing whole‐exome sequencing of the proband. The substitution of cysteine encoding 178th position with tyrosine (p.Cys178Tyr) was caused by this mutation, which was conserved across species. Co‐segregation of disease phenotypes was demonstrated by the family verification. Conclusion: The family diagnosed as SYNS1 was caused by the novel mutation (c.533G>A) of NOG. The combination of clinical diagnosis and molecular diagnosis had improved the understanding of this rare disease and provided a scientific basis for genetic counseling in the family. [ABSTRACT FROM AUTHOR]

Barium (Ba) has been widely and successfully added to three‐way catalysts to effectively control gasoline vehicle emissions. While the introduction of Ba is well‐known to have a very significant impact on three‐way catalysis (TWC) performance, the role of Ba under practical TWC conditions remains insufficiently understood. In this study, we investigated the role of Ba in a Pd‐based catalyst in a standard TWC process using a gasoline vehicle and in situ/operando infrared (IR) spectroscopy. The addition of Ba was found to reduce all of the emissions considered (NOx, CO, and non‐methane hydrocarbons) in the vehicle exhaust gas; it also suppressed supported‐metal aggregation, which is a requirement of a high‐performance catalyst. In addition, IR studies using model powder catalysts revealed that the efficient formation of intermediate surface nitrate species and their subsequent reactions with reductant gases, such as CO, H2, and C3H6 (as a hydrocarbon), play key roles in reducing emissions. This process is akin to the NOx storage and reduction (NSR) mechanism commonly used to control diesel emissions. [ABSTRACT FROM AUTHOR]

HLA‐DPB1*1352:01 differs from HLA‐DPB1*02:01:02:01 by one nucleotide in exon 4. [ABSTRACT FROM AUTHOR]

The article explores The association between COVID-19 and an increased risk of venous thromboembolic (VTE) events, particularly in the critically ill, has been well reported.1 While guidelines exist for thromboprophylaxis during hospitalization, the role for thromboprophylaxis post-hospitalization remains uncertain and controversial.

Objective: To conduct a sub‐cohort analysis to evaluate the efficacy and safety of linaclotide in Chinese patients with constipation‐predominant irritable bowel syndrome (IBS‐C) using data from a completed trial (NCT01880424). Methods: In this phase III, double‐blind, placebo‐controlled trial, IBS‐C patients were randomized to receive linaclotide (290 μg/d) or placebo for 12 weeks. Efficacy was assessed with two co‐primary responder end‐points (12‐wk abdominal pain/discomfort: ≥30% reduction in either score with neither deteriorating from baseline for ≥6 wks; 12‐wk IBS degree of relief: score ≤2 for ≥ 6 wks), seven secondary endpoints and several additional end‐points. Results: In total, 659 Chinese IBS‐C patients received linaclotide (n = 327) or placebo (n = 332). The 12‐week abdominal pain/discomfort end‐point was met in 62.1% and 53.3% of the linaclotide‐treated and placebo‐treated patients, respectively (odds ratio [OR] 1.43, 95% confidence interval [CI] 1.05‐1.96, P = 0.023); the 12‐week IBS degree of relief end‐point was achieved in 32.7% and 16.9% of the patients treated with linaclotide and placebo, respectively (OR 2.40, 95% CI 1.66‐3.47, P < 0.001). The linaclotide‐treated patients had a shorter time to the first spontaneous bowel movement than the placebo‐treated patients (23.6 h vs 43.7 h, P < 0.001). Linaclotide produced significantly greater improvement than placebo in all secondary end‐points from the first 2 weeks (all P < 0.001). Diarrhea was reported in 8.3% of linaclotide‐treated patients and 1.2% of placebo‐treated patients. Conclusion: Linaclotide (290 μg/d) was efficacious and well‐tolerated in Chinese IBS‐C patients with a rapid onset of effect. [ABSTRACT FROM AUTHOR]

The human body contains more than 100 trillion microorganisms, including the oral cavity, the skin, and the gastrointestinal tract. After the gastrointestinal tract, the oral cavity harbors one of the most diverse microbial communities within the human body and harbors more than 770 species of bacteria. The composition of the oral and gut microbiomes is quite different, but there may be a microbiological link between the two mucosal sites during the course of disease. More studies indicate that oral bacteria can disseminate to the distal gut via enteral or hematogenous routes. This is mostly obvious in periodontitis, where specific bacteria, such as Fusobacterium nucleatum and Porphyromonas gingivalis, show this pathogenic feature. The translocation of oral microbes to the gut may give rise to a variety of gastrointestinal diseases, including colorectal cancer. However, the precise role that oral microbe play in colorectal cancer has not been fully illustrated. Here, we summarize the current researches on possible pathways of ectopic gut colonization by oral bacteria and their possible contribution to the pathogenesis of colorectal cancer. Understanding the correlation of the oral‐to‐gut microbial axis in the pathogenesis of colorectal cancer will contribute to precise diagnosis and effective treatment. [ABSTRACT FROM AUTHOR]

SUMMARY: Fruit ripening in tomato (Solanum lycopersicum) is the result of selective expression of ripening‐related genes, which are regulated by transcription factors (TFs). The NAC (NAM, ATAF1/2, and CUC2) TF family is one of the largest families of plant‐specific TFs and members are involved in a variety of plant physiological activities, including fruit ripening. Fruit ripening‐associated NAC TFs studied in tomato to date include NAC‐NOR (non‐ripening), SlNOR‐like1 (non‐ripening like1), SlNAC1, and SlNAC4. Considering the large number of NAC genes in the tomato genome, there is little information about the possible roles of other NAC members in fruit ripening, and research on their target genes is lacking. In this study, we characterize SlNAM1, a NAC TF, which positively regulates the initiation of tomato fruit ripening via its regulation of ethylene biosynthesis. The onset of fruit ripening in slnam1‐deficient mutants created by CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats and CRISPR‐associated protein 9) technology was delayed, whereas fruit ripening in OE‐SlNAM1 lines was accelerated compared with the wild type. The results of RNA‐sequencing (RNA‐seq) and promoter analysis suggested that SlNAM1 directly binds to the promoters of two key ethylene biosynthesis genes (1‐aminocyclopropane‐1‐carboxylate synthase: SlACS2 and SlACS4) and activates their expression. This hypothesis was confirmed by electrophoretic mobility shift assays and dual‐luciferase reporter assay. Our findings provide insights into the mechanisms of ethylene production and enrich understanding of the tomato fruit ripening regulatory network. [ABSTRACT FROM AUTHOR]

Background and Aim: Fusobacterium nucleatum is increasingly being recognized as an important risk factor in colorectal cancer and colorectal adenoma. Endoscopic polypectomy is associated with a decreased incidence of colorectal cancer; however, patients still suffer from a risk of metachronous adenoma. Currently, there are few effective non‐invasive factors that may predict metachronous colorectal adenoma. Here, we evaluated the performance of F. nucleatum in predicting metachronous adenoma. Methods: Fecal samples and clinical information of patients before endoscopic polypectomy were collected from 367 patients in a retrospective cohort, and 238 patients in a prospective cohort. The abundance of fecal F. nucleatum was measured via quantitative polymerase chain reaction. Surveillance colonoscopies were conducted between 1 and 3 years after polypectomy (average follow‐up 27.07 months for the retrospective cohort & 22.57 months for the prospective cohort) to identify metachronous adenoma. Candidate predictive factors and cut‐off value of F. nucleatum abundance were identified from the retrospective cohort and then validated in the prospective cohort. Results: A high abundance of fecal F. nucleatum was found to be an independent risk factor for metachronous adenomas (odds ratio, 6.38; P < 0.001) in the retrospective cohort and was validated in the prospective cohort with a specificity of 65.00%, and a sensitivity of 73.04%, and an overall performance with the area under the curve of 0.73. Conclusion: Fecal abundance of F. nucleatum may be a reliable predictor for metachronous adenoma after endoscopic polypectomy. [ABSTRACT FROM AUTHOR]

Interactions between charged amino acids significantly influence the structure and function of proteins. The encoded charged amino acids Asp, Glu, Arg, and Lys have different number of hydrophobic methylenes linking the backbone to the charged functionality. It remains to be fully understood how does this difference in the number of methylenes affect protein structure stability. Protein secondary structures are the fundamental three‐dimensional building blocks of protein structures. β‐Sheet structures are particularly interesting, because these structures have been associated with a number of protein misfolding diseases. Herein, we report the effect of charged amino acid side chain length at two β‐strand positions individually on the stability of a β‐hairpin. The charged amino acids include side chains with a carboxylate, an ammonium, or a guanidinium group. The experimental peptides, fully folded reference peptides, and fully unfolded reference peptides were synthesized by solid phase peptide synthesis and analyzed by 2D NMR methods including TOCSY, DQF‐COSY, and ROESY. Sequence specific assignments were performed for all peptides. The chemical shift data were used to derive the fraction folded population and the folding free energy for the experimental peptides. Results showed that the fraction folded population increased with increasing charged amino acid side chain length. These results should be useful for developing functional peptides that adopt the β‐conformation. [ABSTRACT FROM AUTHOR]

Previous studies have suggested that gut microbiota plays a critical role in colorectal cancer (CRC). Although preliminary comparisons of the oral and gut microbiota between CRC and healthy control (HC) patients have been made, the association between microbiome abundance and host clinical factors has not been fully illustrated, especially oral health conditions. Matching samples of unstimulated saliva, cancer tissues or biopsies and stools were collected from 30 CRC and 30 HC patients from Shanghai Jiao Tong University affiliated Renji Hospital for 16S rRNA sequencing analysis. The diversity in salivary and mucosal microbiome, but not stool microbiome of CRC group, was significantly different from that of HC, as demonstrated by the Principal Component Analysis. Logistic regression analysis revealed that older age and higher oral hygiene index (OHI) were independent risk factors for CRC, with odds ratios and 95% confidence intervals of 1.159 (1.045‐1.284) and 4.398 (1.328‐14.567), respectively. Salivary Firmicutes to Bacteroides ratio in CRC was significantly higher than that in the HC group (P <.001), while the mucosal ratio was slightly decreased in CRC (P <.05). Salivary Rothia and Streptococcus levels were positively correlated with OHI, while Alloprevotella, Fusobacterium, Peptostreptoccus and Prevotella genera levels were negatively associated with OHI. NetShift analysis revealed that salivary Peptococcus, Centipeda and mucosal Subdoligranulum genus might act as key drivers during the process of carcinogenesis. In conclusion, the current study provides insights into the potential influence of host clinical factors on oral and gut microbiome composition and can be a guide for future studies. What's new? The oral microbiota has been reported to play a critical role in the pathogenesis of colorectal cancer and may provide diagnostic biomarkers. However, oral health status, which might impact the composition of the oral microbiome, is also important to consider. Here, by integrating 16S rRNA sequencing, face‐to‐face questionnaires, and bioinformatics analysis, the authors systematically compared the oral and gut microbiota of colorectal cancer patients with healthy controls. In addition, they analysed the associations between several hosts' clinical parameters and the 50 most abundant oral and gut genera, providing potential diagnostic and therapeutic targets for colorectal cancer. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 30-year-old woman presented to the First Affiliated Hospital of Dalian Medical University with complaints of right hip pain for 3 months and fatigue for 1 week on December 28, 2017. Topics discussed include the patient had BCRABL1 fusion gene not only in the BM cells but also on the hip biopsy tissues; and she had double Ph chromosome in the fusion variant cell, we did FISH on BM cells at metaphase.

Dynamic vulcanized thermoplastic polyurethane (TPU)/methyl vinyl silicone rubber (MVQ) thermoplastic vulcanizates (TPVs) were prepared in torque rheometer. The influence of the type and amount of peroxide crosslinking agent on the mechanical properties, thermal stability, micromorphology and melt flowability was systematically investigated. The results showed that the mechanical properties of the TPVs vulcanized by 2,5‐dimethyl‐2,5‐di (tert‐butyl peroxy) hexane (DBPH) first increased and then decreased with increasing the peroxide amount, while for dicumyl peroxide (DCP) vulcanizing system the mechanical properties slowly increased. Besides, the comprehensive mechanical properties vulcanized by DBPH were better than those of DCP group. The results of the thermogravimetric analysis showed that the TPVs vulcanized by DBPH had better heat stability, corresponding to the excellent thermo‐oxidative aging performance and the 38% increase in tensile strength after aging. In addition, the MVQ rubber particles showed better dispersing performance for DBPH vulcanizing system. The melt flow rate of the TPVs showed a linear relationship with increasing DBPH dosage and became worse after the amount of crosslinking agent exceeded 1.5 phr. By comprehensive comparison, the TPVs have better performance when use peroxide DBPH as the crosslinking agent and the dosage is 1.5 phr. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy (DR) is one of the leading causes of blindness worldwide, and the limited availability of qualified ophthalmologists restricts its early diagnosis. For the past few years, artificial intelligence technology has developed rapidly and has been applied in DR screening. The upcoming technology provides support on DR screening and improves the identification of DR lesions with a high sensitivity and specificity. This review aims to summarize the progress on automatic detection and classification models for the diagnosis of DR. [ABSTRACT FROM AUTHOR]

Studies showed that the increase of myeloid‐derived suppressor cells (MDSCs) in tumour microenvironment is closely related to the resistant treatment and poor prognosis of metastatic breast cancer. However, the effect of tumour‐derived exosomes on MDSCs and its mechanism are not clear. Here, we reported that breast cancer cells (4T1)‐secreted exosomes (BCC‐Ex) were able to differentiate bone marrow cells into MDSCs and significantly inhibited the proliferation of T lymphocytes to provide an immunosuppressive microenvironment for cancer cells in vivo and in vitro. The number of MDSCs in bone marrow and spleen of 4T1 tumour‐bearing mice and BCC‐Ex infused mice was significantly higher than that of normal mice, whereas the number of T lymphocytes in spleen was significantly decreased. In addition, BCC‐Ex markedly promoted the differentiation of MDSCs from bone marrow cells or bone marrow cells derived macrophages, seen as the increased expressions of MDSCs‐related functional proteins Arginase‐1 (Arg‐1) and inducible nitric oxide synthase (iNOS). Furthermore, BCC‐Ex significantly down‐regulated the expressions of chemokine receptor CXCR4 and markedly up‐regulated the levels of inflammatory cytokines IL‐6 and IL‐10 in bone marrow cells and macrophages and remarkably inhibited the division and proliferation of T cells. Importantly, CXCR4 agonist, CXCL12, could reverse the function of BCC‐Ex, indicating that BCC‐Ex‐induced MDSCs might be dependent on the down‐regulation of CXCR4. Western blot showed that BCC‐Ex significantly promoted the phosphorylation of STAT3 in bone marrow cells, resulting in the inhibitions of the proliferation and apoptosis of bone marrow cells, and the aggravation of the differentiation of bone marrow cells into MDSCs. [ABSTRACT FROM AUTHOR]

Objective: Emperipolesis is a pathological feature for the diagnosis of autoimmune hepatitis (AIH). We have previously found that CD8+ T cells participated in the emperipolesis in AIH. In this study we aimed to clarify the characteristics and molecular mechanisms of emperipolesis in patients with AIH in vitro and in mice with α‐Galactosylceramide (α‐GalCer)‐induced acute hepatitis. Methods: The peripheral blood mononuclear cells (PBMC) of patients with various chronic liver diseases and healthy controls were co‐cultured with hepatic cell lines to induce emperipolesis in vitro. Confocal staining was performed to illustrate the cellular types and potential mechanisms of emperipolesis in AIH. In addition, a murine model of α‐GalCer‐induced acute hepatitis that mimics human AIH was used to confirm the role of CD44/p‐ERM/F‐actin in the emperipolesis process in vivo. Results: In the co‐cultured system of PBMC and hepatic cell line, emperipolesis was observed most commonly in patients with AIH. The main cells participating in emperipolesis were CD8+ T cells, and they penetrated hepatic cells actively via the CD44/p‐ERM/F‐actin pathway. As a result, most CD8+ T cells engulfed by hepatic cells underwent apoptosis. In the α‐GalCer‐induced acute hepatitis model, emperipolesis was observed around the inflammatory foci and was inhibited by the ezrin phosphorylation inhibitor NSC668394. Similarly, activated murine CD8+ T cells penetrated primary hepatocytes via the CD44/p‐ERM/F‐actin pathway in vitro. Conclusions: CD8+ T cells penetrate hepatic cells actively via the CD44/p‐ERM/F‐actin signaling pathway and undergo apoptosis. This may be a compensatory mechanism to attenuate the overwhelming immune attack in AIH. [ABSTRACT FROM AUTHOR]

During this coronavirus disease 2019 (COVID‐19) pandemic, physicians have the important task of risk stratifying patients who present with acute respiratory illnesses. Clinical presentation of COVID‐19, however, can be difficult to distinguish from other respiratory viral infections. Thus, identifying clinical features that are strongly associated with COVID‐19 in comparison to other respiratory viruses can aid risk stratification and testing prioritization especially in situations where resources for virological testing and resources for isolation facilities are limited. In our retrospective cohort study comparing the clinical presentation of COVID‐19 and other respiratory viral infections, we found that anosmia and dysgeusia were symptoms independently associated with COVID‐19 and can be important differentiating symptoms in patients presenting with acute respiratory illness. On the other hand, laboratory abnormalities and radiological findings were not statistically different between the two groups. In comparing outcomes, patients with COVID‐19 were more likely to need high dependency or intensive care unit care and had a longer median length of stay. With our findings, we emphasize that epidemiological risk factors and clinical symptoms are more useful than laboratory and radiological abnormalities in differentiating COVID‐19 from other respiratory viral infections. Highlights: Ansomia and dysgeusia are important differentiating symptoms for coronavirus disease 2019 (COVID‐19) from other respiratory viruses.Epidemiology history and clinical symptoms are important in the risk stratification of patients who present with acute respiratory illness.Initial laboratory and radiological findings are less important in risk stratification. [ABSTRACT FROM AUTHOR]