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Intestinal dysfunction is frequently driven by abnormalities of specific genes, microbiota, or microenvironmental factors, which usually differ across individuals, as do intestinal physiology and pathology. Therefore, it's necessary to develop personalized therapeutic strategies, which are currently limited by the lack of a simulated intestine model. The mature human intestinal mucosa is covered by a single layer of columnar epithelial cells that are derived from intestinal stem cells (ISCs). The complexity of the organ dramatically increases the difficulty of faithfully mimicking in vivo microenvironments. However, a simulated intestine model will serve as an indispensable foundation for personalized drug screening. In this article, we review the advantages and disadvantages of conventional 2-dimensional models, intestinal organoid models, and current microfluidic intestine-on-a-chip (IOAC) models. The main technological strategies are summarized, and an advanced microfluidic primary IOAC model is proposed for personalized intestinal medicine. In this model, primary ISCs and the microbiome are isolated from individuals and co-cultured in a multi-channel microfluidic chip to establish a microengineered intestine device. The device can faithfully simulate in vivo fluidic flow, peristalsis-like motions, host-microbe crosstalk, and multi-cell type interactions. Moreover, the ISCs can be genetically edited before seeding, and monitoring sensors and post-analysis abilities can also be incorporated into the device to achieve high-throughput and rapid pharmaceutical studies. We also discuss the potential future applications and challenges of the microfluidic platform. The development of cell biology, biomaterials, and tissue engineering will drive the advancement of the simulated intestine, making a significant contribution to personalized medicine in the future. Graphical abstract The intestine is a primary organ for digestion, absorption, and metabolism, as well as a major site for the host-commensal microbiota interaction and mucosal immunity. The complexity of the organ dramatically increases the difficulty of faithfully mimicking in vivo microenvironments, though physiological 3-dimensional of the native small intestinal epithelial tissue has been well documented. An intestinal stem cells-based microfluidic intestine-on-a-chip model that faithfully simulate in vivo fluidic flow, peristalsis-like motions, host-microbe crosstalk, and multi-cell type interactions will make a significant contribution., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Quinolones (QNs), dechloranes (DECs), and chlorinated paraffins (CPs) are three kinds of new halogenated organic pollutants (HOPs), which originate from the use of flame retardants, lubricants and pesticides. Since QNs, DECs, and CPs are frequently detected in waters and sediments, it is necessary to investigate the toxic effects of these HOPs with dwelling phytoplankton, especially for cyanobacteria, to explore their potential hormetic effects and contributions to algal blooms. In the present study, we investigate single and joint toxicity of QNs, DECs and CPs on Microcystis aeruginosa (M. aeruginosa), a cyanobacterium that is frequently implicated with algal blooms. The results indicate single QNs and DECs induce marked hormetic effects on the proliferation of M. aeruginosa but CPs do not. The stimulatory effect of hormesis is linked with accelerated replication of DNA, which is considered to stem from the moderate rise in intracellular reactive oxygen species (ROS). Joint toxicity tests reveal that both QNs & CPs mixtures and DECs & CPs mixtures show hormetic effects on M. aeruginosa, but QNs & DECs mixtures show no hormetic effect. QNs & DECs mixtures exhibit synergistic toxic actions, which may be caused by a sharp rise in intracellular ROS simultaneously produced by the agents. Joint toxic actions of both QNs & CPs, and DECs & CPs shift from addition to antagonism as concentration increases, and this shift may mainly depend on the influence of CPs on cell membrane hydrophobicity of M. aeruginosa. This study provides data and toxic mechanisms for the hormetic phenomenon of single and joint HOPs on M. aeruginosa. The hormetic effects of HOPs may benefit the proliferation of M. aeruginosa in the aquatic environment, aggravating the formation of algal blooms. This study also reflects the important role of hormesis in environmental risk assessment of pollutants., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Vascular adhesion protein-1 (VAP-1) is an inflammation-inducible adhesion molecule, which supports contact between leukocytes and inflamed endothelium. There is evidence that VAP-1 is involved in the recruitment of leukocytes to melanoma tumors. Interleukin-2 (IL-2)-based immunotherapy is an efficient therapy that promotes immune system activity against cancers but is associated with toxicity. In the present study, we evaluated the feasibility of PET/CT imaging using the radiotracer [ 68 Ga]Ga-DOTA-Siglec-9, which is targeted to VAP-1, to monitor pharmacodynamic effects of a novel FAP-IL2v immunocytokine (a genetically engineered variant of IL-2 fused with fibroblast activation protein) in the B16-FAP melanoma model. At 9 days after the inoculation of B16-FAP melanoma cells, mice were studied with [ 68 Ga]Ga-DOTA-Siglec-9 PET/CT as a baseline measurement. Immediately after baseline imaging, mice were treated with FAP-IL2v or vehicle, and treatment was repeated 3 days later. Subsequent PET/CT imaging was performed 3, 5, and 7 days after baseline imaging. In addition to in vivo PET imaging, ex vivo autoradiography, histology, and immunofluorescence staining were performed on excised tumors. B16-FAP tumors were clearly detected with [ 68 Ga]Ga-DOTA-Siglec-9 PET/CT during the follow-up period, without differences in tumor volume between FAP-IL2v-treated and vehicle-treated groups. Tumor-to-muscle uptake of [ 68 Ga]Ga-DOTA-Siglec-9 was significantly higher in the FAP-IL2v-treated group than in the vehicle-treated group 7 days after baseline imaging, and this was confirmed by tumor autoradiography analysis. FAP-IL2v treatment did not affect VAP-1 expression on the tumor vasculature. However, FAP-IL2v treatment increased the number of CD8 + T cells and natural killer cells in tumors. The present study showed that [ 68 Ga]Ga-DOTA-Siglec-9 can detect B16-FAP tumors and allows monitoring of FAP-IL2v treatment., Competing Interests: SJ owns stock in Faron Pharmaceuticals. CK, VN, and MR declare employment, patents and ownership interest with Roche, and TN was employed by Roche at the time of the study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Viitanen, Virtanen, Liljenbäck, Moisio, Li, Nicolini, Richard, Klein, Nayak, Jalkanen and Roivainen.)

Background: Operation is the primary therapeutic option for patients with distal gastrectomy. Braun anastomosis is usually performed after Billroth II reconstruction, which is wildly applied on distal gastrectomy because it is believed to benefit patients. However, studies are needed to confirm that., Aim: To identify whether the addition of Braun anastomosis to Billroth II reconstruction on laparoscopy-assisted distal gastrectomy benefits patients., Methods: A total of 143 patients with gastric cancer underwent laparoscopy-assisted distal gastrectomy at Centre 1 of PLA general hospital between January 2015 and December 2019. Clinical data of the patients were collected, and 93 of the 143 patients were followed up. These 93 patients were divided into two groups: Group 1 (Billroth II reconstruction, 33 patients); and Group 2 (Billroth II reconstruction combined with Braun anastomosis, 60 patients). Postoperative complication follow-up data and relevant clinical data were compared between the two groups., Results: There were no significant differences between Group 1 and Group 2 in postoperative complications (6.1% vs 6.7%, P = 0.679), anal exhaust time or blood loss. The follow-up prevalence of reflux gastritis indicated no significant difference between Group 1 and Group 2 (68.2% vs 51.7%, P = 0.109). The follow-up European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 scores revealed no evident difference between Group 1 and Group 2 as well. Group 1 had a shorter operating time than Group 2 on average (234.6 min vs 262.0 min, P = 0.017)., Conclusion: Combined with Billroth II reconstruction, Braun anastomosis has been applied due to its ability to reduce the prevalence of reflux gastritis. Whereas in this study, the prevalence of reflux gastritis showed no significant difference, leading to a conclusion that under the circumstance of Braun anastomosis costing more time and more money, simple Billroth II reconstruction should be widely applied., Competing Interests: Conflict-of-interest statement: We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Luffa sponge gourd ( Luffa cylindrica ) is an important cucurbitaceous vegetable and is known as the source of loofah. From 2020 to 2021, a leaf disease occurred on luffa leaves in the Hunan Province of China. Symptoms were displayed as oval to irregular chlorotic lesions surrounded by yellow halos. The pathogens were isolated from the affected leaves. According to morphological characterization and molecular identification using multi-locus phylogenetic analysis of the internal transcribed spacer (ITS), actin ( ACT ), chitin synthase ( CHS-1 ), glyceraldehyde-3-phosphate dehydrogenase ( GAPDH ), β-tubulin ( TUB2 ), and partial mating type (Mat1-2) gene ( ApMAT ) regions, the pathogens were identified as two Colletotrichum species: Colletotrichum fructicola and C. siamense . Koch's postulates were identified by a pathogenicity test and re-confirmation. To the best of our knowledge, C. fructicola and C. siamense are two new species associated with luffa sponge gourd anthracnose.

Background: For non-small cell lung cancer (NSCLC) patients on antithrombotic therapy who are treated with microwave ablation (MWA), the transient interruption of antithrombotic agents may increase the risk of thromboembolism, and continuation of antithrombotic agents may increase the risk of intraprocedural hemorrhage. This retrospective cohort study aimed to explore the safety of MWA in patients with NSCLC on antithrombotic therapy., Methods: A total of 572 patients with NSCLC (antithrombotic therapy group: n=84, Group A; control group: n=488, Group B) who received MWA were included. Antithrombotic agent use was suspended before MWA and resumed as soon as possible after MWA. Hemorrhagic (hemothorax and hemoptysis) and thromboembolic complications (pulmonary embolism, cerebral infarction, and angina) were compared. Logistic regression analyses were used to investigate the predictors of hemorrhagic complications after MWA., Results: Hemorrhagic complications occurred in 8 participants (9.5%) from Group A and 33 participants (6.8%) from Group B, and no statistically significant difference was found (P=0.365). There were 3 participants (0.5%) who developed thromboembolic complications, including 1 case (1.2%, 1/84) of pulmonary embolism in Group A, and 2 cases (0.4%, 2/488) of cerebral infarction or angina in Group B; no significant difference was found (P=0.923). In the subgroup analyses of Group A, no statistically significant difference of hemorrhagic (P>0.999) or thromboembolic complications (P>0.999) was found between patients who received and did not receive bridging anticoagulation with heparin. Logistic regression analyses revealed that direct contact of a tumor with vessels ≥2 mm was a predictor of hemorrhagic complications [hazard ratio (HR) =2.318; 95% confidence interval (CI): 1.215-4.420; P=0.011], while antithrombotic therapy was irrelevant., Conclusions: With the appropriate cessation and resumption of antithrombotic agents, patients with NSCLC on antithrombotic therapy have comparable incidence rates of hemorrhagic and thromboembolic complications after MWA to those of patients who are not on antithrombotic therapy. Therefore, with appropriate cessation, MWA appears to generally be safe for NSCLC patients on antithrombotic therapy., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-21-1043/coif). The authors have no conflicts of interest to declare., (2022 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Objective To analyze maternal blood exposure to non-therapeutic antibiotics in late pregnancy and explore the effects of low-dose antibiotics on fetal growth and development.Methods A total of 104 pregnant women in late pregnancy (28-32 weeks) without serious pregnancy complications were enrolled,who had regular antenatal examination and delivery in Peking Union Medical College Hospital and did not use therapeutic antibiotics 2 months before pregnancy and in the whole pregnant process.The levels of antibiotics in the maternal blood were detected by liquid chromatography-tandem mass spectrometry,and the pregnant women were assigned into an antibiotic exposure group (antibiotic positive) and a non-exposure group (antibiotic negative).The length,weight,placental weight,and placental volume of the newborns in the two groups were measured,and the data were statistically analyzed by t test or χ 2 test.Results The maternal blood antibiotic test showed 7 positive cases (6.73%,antibiotic exposure group) and 97 negative cases (93.27%,non-exposure group). The average length of newborns in the antibiotic exposure group and the non-exposure group was (49.57±1.40) cm and (48.85±1.77) cm,respectively,with no significant difference ( t =1.060, P =0.363).The average weight of newborns in the antibiotic exposure group and the non-exposure group was (3558.57±382.95) g and (3275.36±356.41) g,respectively,with significant difference ( t =2.021, P =0.046).The mean placental weight in the antibiotic exposure group and the non-exposure group was (676.43±124.59) g and (631.96±129.25) g,respectively,with no significant difference ( t =0.881, P =0.380).The mean placental volume in the antibiotic exposure group and the non-exposure group was (724.67±174.91) cm 3 and (676.82±220.86) cm 3 ,respectively,with no significant difference ( t =0.560, P =0.388).Compared with those in the non-exposure group,the neonatal length,neonatal weight,placental weight,and placental volume in the antibiotic exposure group increased by 1.47%,8.65%,7.04%,and 7.07%,respectively.Conclusion There are antibiotics in the environment,and maternal blood exposure to non-therapeutic antibiotics can promote the growth and development of the fetus and placenta,especially increasing the fetal weight.

Background: Oseltamivir resistance in influenza virus (IFV) has been of widespread concern. An increase in the frequency of viruses with reduced inhibition was observed. Whether oseltamivir is effective is uncertain. We conducted this study to understand the real-world situation in northern China and the clinical efficacy for patients with IFV infection after the use of oseltamivir., Methods: The longitudinal study was performed on influenza-like illness (ILI) cases in a tertiary general hospital in Beijing, China during the flu season of 2018-2019. All ILI cases (≥18 years) were recruited into the study. We analyzed the effect of the oseltamivir therapy on the number of clinic visits, hospitalization frequency, and the duration of fever and cough., Results: A total of 689 ILI patients were recruited in this study with 355 in the oseltamivir therapy group and 334 in the supportive therapy group. Among the ILI patients, 388 patients were detected for IFV infection (364 IFV-A and 24 IFV-B) and divided into two groups with or without the oseltamivir therapy (302 vs. 86). There were no significant differences in the basic characteristics between the oseltamivir and supportive therapy groups in the ILI patients or in the IFV positive patients (all p  < 0.05). After adjusting for the potential confounders, oseltamivir therapy reduced the times of clinic visits in the ILI and IFV positive patients ( p  = 0.043 and p  = 0.011). No effectiveness with oseltamivir therapy was observed in the outcomes of hospitalization frequency, and the duration of fever and cough., Conclusion: Oseltamivir use may reduce the times of clinic visits. However, we did not observe the differences in the duration of fever, cough, and the frequency of hospitalization between oseltamivir therapy and supportive therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Chen, Wang, Lin, Li, Liang, Deng, Zhang, Jia, Su, Kang, Du, Liu, Xu and Lu.)

Hybrid halide perovskites have emerged as highly promising photovoltaic materials because of their exceptional optoelectronic properties, which are often optimized via compositional engineering like mixing halides. It is well established that hybrid perovskites undergo a series of structural phase transitions as temperature varies. In this work, the authors find that phase transitions are substantially suppressed in mixed-halide hybrid perovskite single crystals of MAPbI 3-x Br x (MA = CH 3 NH 3 + and x = 1 or 2) using a complementary suite of diffraction and spectroscopic techniques. Furthermore, as a general behavior, multiple crystallographic phases coexist in mixed-halide perovskites over a wide temperature range, and a slightly distorted monoclinic phase, hitherto unreported for hybrid perovskites, is dominant at temperatures above 100 K. The anomalous structural evolution is correlated with the glassy behavior of organic cations and optical phonons in mixed-halide perovskites. This work demonstrates the complex interplay between composition engineering and lattice dynamics in hybrid perovskites, shedding new light on their unique properties., (© 2022 The Authors. Small published by Wiley-VCH GmbH.)

Under the changing climate scenario, changes in precipitation regimes are expected to alter soil water and salinity conditions, with consequences on the characteristics of plant community in estuarine wetland. Here, we used a six-year (2015-2020) precipitation manipulation experiment to examine how plant community characteristics responded to precipitation changes in the Yellow River Delta. The results showed that soil electrical conductivity significantly decreased, while soil moisture significantly increased with increasing precipitation. Precipitation changes altered plant community composition. Increased precipitation reduced the absolute dominance of Suaeda glauca and Suaeda salsa , but increased that of Triarrhena sacchariflora and Imperata cylindrica . Shannon index and Margalef richness index of plant community significantly increased with increasing precipitation. Compared with the control, both decreased and increased precipitation decreased the plant community abundance, frequency and coverage. The treatment of 60% increased precipitation significantly decreased plant community frequency by 54.9%, while the 60% decreased precipitation, 40% decreased precipitation, 40% increased precipitation and 60% increased precipitation treatment significantly decreased plant abundance by 38.9%, 33.8%, 35.8% and 45.7%, respectively. The aboveground biomass significantly increased with increasing precipitation, but aboveground plant biomass under 60% increased precipitation treatment being lower than that reducing under 40% increased precipitation treatment, probably due to the negative effects of flooding stress. In addition, Margalef richness index had a significantly positive relationship with aboveground biomass. Aboveground biomass, Shannon diversity index, Margalef richness index, and Simpson diversity index were negatively related to soil electrical conductivity, and aboveground plant biomass was positively related to soil moisture. Our results revealed that precipitation changes regulate growth characteristics, species composition, and diversity of plant community by altering soil water and salinity conditions in a coastal wetland.

Although autogenous nerve transplantation is the gold standard for treating peripheral nerve defects of considerable length, it still has some shortcomings, such as insufficient donors and secondary injury. Composite chitosan scaffolds loaded with controlled release of nerve growth factor can promote neuronal survival and axonal regeneration after short-segment sciatic nerve defects. However, the effects on extended nerve defects remain poorly understood. In this study, we used chitosan scaffolds loaded with nerve growth factor for 8 weeks to repair long-segment (20 mm) sciatic nerve defects in adult rats. The results showed that treatment markedly promoted the recovery of motor and sensory functions. The regenerated sciatic nerve not only reconnected with neurons but neural circuits with the central nervous system were also reconstructed. In addition, the regenerated sciatic nerve reconnected the motor endplate with the target muscle. Therefore, this novel biomimetic scaffold can promote the regeneration of extended sciatic nerve defects and reconstruct functional circuits. This provides a promising method for the clinical treatment of extended peripheral nerve injury. This study was approved by the Animal Ethics Committee of Capital Medical University, China (approval No. AEEI-2017-033) on March 21, 2017., Competing Interests: None

Background: The studies of laparoscopic-assisted transhiatal gastrectomy (LTG) in patients with Siewert type II adenocarcinoma of the esophagogastric junction (AEG) are scarce., Aim: To compare the surgical efficiency of LTG with the open transhiatal gastrectomy (OTG) for patients with Siewert type II AEG., Methods: We retrospectively evaluated a total of 578 patients with Siewert type II AEG who have undergone LTG or OTG at the First Medical Center of the Chinese People's Liberation Army General Hospital from January 2014 to December 2019. The short-term and long-term outcomes were compared between the LTG ( n = 382) and OTG ( n = 196) groups., Results: Compared with the OTG group, the LTG group had a longer operative time but less blood loss, shorter length of abdominal incision and an increased number of harvested lymph nodes ( P < 0.05). Patients in the LTG group were able to eat liquid food, ambulate, expel flatus and discharge sooner than the OTG group ( P < 0.05). No significant differences were found in postoperative complications and R0 resection. The 3-year overall survival and disease-free survival performed better in the LTG group compared with that in the OTG group (88.2% vs 79.2%, P = 0.011; 79.7% vs 73.0%, P = 0.002, respectively). In the stratified analysis, both overall survival and disease-free survival were better in the LTG group than those in the OTG group for stage II/III patients ( P < 0.05) but not for stage I patients., Conclusion: For patients with Siewert type II AEG, LTG is associated with better short-term outcomes and similar oncology safety. In addition, patients with advanced stage AEG may benefit more from LTG in the long-term outcomes., Competing Interests: Conflict-of-interest statement: All authors declare that there is no conflict of interest., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Crassaminicella sp. 143-21, a putative new species isolated from deep-sea hydrothermal vent chimney on the Central Indian Ridge (CIR), is an anaerobic, thermophilic and rod-shaped bacterium belonging to the family Clostridiaceae. In this study, we present the complete genome sequence of strain 143-21, comprising 2,756,133 bp with a G + C content of 31.1%. In total, 2427 protein coding genes, 121 tRNA genes and 33 rRNA genes were obtained. Genomic analysis of strain 143-21 revealed that numerous genes related to organic matter transport and catabolism, including peptide transport, amino acid transport, saccharide transport, ethanolamine transport and corresponding metabolic pathways. Further, the genome contains a large proportion of genes involved in translation, ribosomal structure, and signal transduction. These genes might facilitate microbial survival in deep-sea hydrothermal vent environment. The genome of strain 143-21 will be helpful for further understanding its adaptive strategies in the deep-sea hydrothermal vent environment., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Capsule of alkaloids from leaf of Alstonia scholaris (CALAS) is a new investigational botanical drug (No. 2011L01436) for respiratory disease. Clinical population pharmacokinetics (PK), metabolomics and therapeutic data are essential to guide dosing in patients. Previous research has demonstrated the potential therapeutic effect of CALAS on acute bronchitis. Further clinical trial data are needed to verify its clinical efficacy, pharmacokinetics behavior, and influence of dosage and other factors., Purpose: To verify the clinical efficacy and explore the potential biomarkers related to CALAS treatment for acute bronchitis., Materials and Methods: Oral CALAS was assessed in a randomized, double-blind, placebo-controlled trial. Fifty-five eligible patients were randomly assigned to four cohorts to receive 20, 40 or 80 mg, of CALAS three times daily for seven days, or placebo. Each CALAS cohort included 15 subjects, and the placebo group included 10 subjects. A population PK model of CALAS was developed using plasma with four major alkaloid components. Metabolomics analysis was performed to identify biomarkers correlated with the therapeutic effect of CALAS, and efficacy and safety were assessed based on clinical symptoms and adverse events., Results: The symptoms of acute bronchitis were alleviated by CALAS treatment without serious adverse events or clinically significant changes in vital signs, electrocardiography or upper abdominal Doppler ultrasonography. Moreover, one compartment model with first-order absorption showed that an increase in aspartate transaminase will reduce the clearance (CL) of scholaricine, and picrinine CL was inversely proportional to body mass index, while 19-epischolaricine and vallesamine CL increased with aging. The serum samples from acute bronchitis patients at different time points were analyzed using UPLC-QTOF in combination with the orthogonal projection to latent structures-discriminant analysis, which indicated higher levels of lysophosphatidylcholines, lysophosphatidylethanolamines and amino acids with CALAS treatment than with placebo., Conclusion: This is the first study to evaluate the clinical efficacy and explored the potential biomarkers related to CALAS therapeutic mechanism of acute bronchitis by means of clinical trial combined the metabolomics study. This exploratory study provides a basis for further research on clinical efficacy and optimal dosing regimens based on pharmacokinetics behavior. Additional acute bronchitis patients and CALAS PK samples collected in future studies may be used to improve model performance and maximize its clinical value., (Copyright © 2022. Published by Elsevier GmbH.)

Background: While the correlation between PD-L1 expression and KRAS mutation has been previously reported in other solid tumors such as non-small cell lung cancer (NSCLC), whether PD-L1 can be modulated by ERK signaling downstream of KRAS in intrahepatic cholangiocarcinoma (iCCA) and the underlying molecular regulatory mechanism remain unclear., Methods: The expression of ERK, p-ERK, PD-L1 and autophagy markers following KRAS knockdown or Ras/Raf/MEK/ERK signaling inhibitors treatment was examined in two human iCCA cell lines (HuCCT1 and RBE) using western blotting and immunofluorescence. Both pharmacological autophagy inhibitors and short-interfering RNA against ATG7 were applied to inhibit autophagy. The apoptosis rates of iCCA cell lines were detected by flow cytometry and CCK-8 after co-culturing with CD3/CD28-activated human CD8 + T lymphocytes. Immunohistochemistry was applied to detect the correlation of ERK, p-ERK and PD-L1 in 92 iCCA tissues., Results: The present study demonstrated that the PD-L1 expression level was distinctly reduced in KRAS-mutated iCCA cell lines when ERK signaling was inhibited and ERK phosphorylation levels were lowered. The positive association between p-ERK and PD-L1 was also verified in 92 iCCA tissue samples. Moreover, ERK inhibition induced autophagy activation. Both inhibiting autophagy via autophagy inhibitors and genetically silencing the ATG7 expression partially reversed the reduced PD-L1 expression caused by ERK inhibition. In addition, ERK-mediated down-regulation of PD-L1 via autophagy pathways induced the apoptosis of iCCA cells when co-cultured with CD3/CD28-activated human CD8 + T lymphocytes in vitro., Conclusions: Our results suggest that ERK signaling inhibition contributes to the reduction of PD-L1 expression through the autophagy pathway in iCCA. As a supplement to anti-PD-1/PD-L1 immunotherapy, ERK-targeted therapy may serve as a potentially novel treatment strategy for human KRAS-mutated iCCA., (© 2022. The Author(s).)

Purpose: To compare the outcomes of drug-eluting bead bronchial arterial chemoembolization (DEB-BACE) with and without microwave ablation (MWA) for the treatment of advanced and standard treatment-refractory/ineligible non-small cell lung cancer (ASTRI-NSCLC)., Materials and Methods: A total of 77 ASTRI-NSCLC patients who received DEB-BACE combined with MWA (group A; n = 28) or DEB-BACE alone (group B; n = 49) were included. Clinical outcomes were compared between groups A and B. Kaplan-Meier methods were used to compare the median progression-free survival (PFS) or overall survival (OS) between the two groups. Univariate and multivariate Cox proportional hazards analyses were used to investigate the predictors of OS for ASTRI-NSCLC treated with DEB-BACE., Results: No severe adverse event was found in both groups. Pneumothorax was the predominant MWA-related complication in group A, with an incidence rate of 32.1% (9/28). Meanwhile, no significant difference was found in DEB-BACE-related complications between groups A and B. The overall disease control rate (DCR) was 61.0% (47/77), with a significantly higher DCR in group A (85.7% vs. 46.9%, P = 0.002). The median PFS in groups A and B was 7.0 and 4.0 months, respectively, with a significant difference ( P = 0.037). The median OS in groups A and B was both 8.0 months, with no significant difference ( P = 0.318). The 6-month PFS and OS rates in groups A and B were 75.0% and 78.6%, 22.4% and 59.2%, respectively, while the 12-month PFS and OS rates in groups A and B were 17.9% and 28.6%, 14.3% and 22.4%, respectively. Of these, a significantly higher 6-month PFS rate was found in group A (75.0% vs. 22.4%; P < 0.001). The cycles of DEB-BACE/bronchial artery infusion chemotherapy [hazard ratio (HR): 0.363; 95% confidence interval (CI): 0.202-0.655; P = 0.001] and postoperative immunotherapy (HR: 0.219; 95% CI: 0.085-0.561; P = 0.002) were identified as the predictors of OS in ASTRI-NSCLC treated with DEB-BACE., Conclusion: MWA sequentially combined with DEB-BACE was superior to DEB-BACE alone in the local control of ASTRI-NSCLC. Although the combination therapy reveals a trend of prolonging the OS, long-term prognosis warrants an investigation with a longer follow-up., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xu, Bie, Li, Li, Kong, Peng and Li.)

Background: The ideal treatment strategy for stable three-vessel coronary artery disease (CAD) patients are difficult to determine and for patients undergoing conservative treatment, imaging evidence of coronary atherosclerotic severity progression remains limited. Epicardial fat volume (EFV) on coronary CT angiography (CCTA) has been considered to be associated with coronary atherosclerosis. Therefore, this study aims to evaluate the relationship between EFV level and coronary atherosclerosis severity in three-vessel CAD., Methods: This retrospective study enrolled 252 consecutive patients with three-vessel CAD and 252 normal control group participants who underwent CCTA between January 2018 and December 2019. A semi-automatic method was developed for EFV quantification on CCTA images, standardized by body surface area. Coronary atherosclerosis severity was evaluated and scored by the number of coronary arteries with ≥ 50% stenosis on coronary angiography. Patients were subdivided into groups on the basis of lesion severity: mild (score = 3 vessels, n = 85), moderate (3.5 vessels ≤ score < 4 vessels, n = 82), and severe (4 vessels ≤ score ≤ 7 vessels, n = 85). The independent sample t-test, analysis of variance, and logistic regression analysis were used to evaluate the associations between EFV level and severity of coronary atherosclerosis., Results: Compared with normal controls, three-vessel CAD patients had significantly higher EFV level (65 ± 22 mL/m 2 vs. 48 ± 19 mL/m 2 ; P < 0.001). In patients with three-vessel CAD, there was a progressive decline in EFV level as the score of coronary atherosclerosis severity increased, especially in those patients with a body mass index (BMI) ≥ 25 kg/m 2 (75 ± 21 mL/m 2 vs. 72 ± 22 mL/m 2 vs. 62 ± 17 mL/m 2 ; P < 0.05). Multivariable regression analysis showed that both BMI (OR 3.40, 95% CI 2.00-5.78, P < 0.001) and the score of coronary atherosclerosis severity (OR 0.49, 95% CI 0.26-0.93, P < 0.05) were independently related to the change of EFV level., Conclusion: Three-vessel CAD patients do have higher EFV level than the normal controls. While, there may be an inverse relationship between EFV level and the severity of coronary atherosclerosis in patients with three-vessel CAD., (© 2022. The Author(s).)

Background: COVID-19 has caused more than 2.6 billion infections and several million deaths since its outbreak 2 years ago. We know very little about the long-term cellular immune responses and the kinetics of neutralizing antibodies (NAbs) to SARS-CoV-2 because it has emerged only recently in the human population., Methods: We collected blood samples from individuals who were from the first wave of the COVID-19 epidemic in Wuhan between December 30, 2019, and February 24, 2020. We analyzed NAbs to SARS-CoV-2 using pseudoviruses and IgG antibodies to SARS-CoV-2 spike (S) and nucleocapsid (N) protein using enzyme-linked immunosorbent assay in patients' sera and determined SARS-CoV-2-specific T-cell responses of patients with ELISpot assays., Results: We found that 91.9% (57/62) and 88.9% (40/45) of COVID-19 patients had NAbs against SARS-CoV-2 in a year (10-11 months) and one and a half years (17-18 months), respectively, after the onset of illness, indicating that NAbs against SARS-CoV-2 waned slowly and possibly persisted over a long period time. Over 80% of patients had IgG antibodies to SARS-CoV-2 S and N protein one and a half years after illness onset. Most patients also had robust memory T-cell responses against SARS-CoV-2 one and a half years after the illness. Among the patients, 95.6% (43/45) had an IFN-γ-secreting T-cell response and 93.8% (15/16) had an IL-2-secreting T-cell response. The T-cell responses to SARS-CoV-2 were positively correlated with antibodies (including neutralizing antibodies and IgG antibodies to S and N protein) in COVID-19 patients. Eighty percent (4/5) of neutralizing antibody-negative patients also had SARS-CoV-2-specific T-cell response. After long-term infection, protective immunity was independent of disease severity, sex, and age., Conclusions: We concluded that SARS-CoV-2 infection elicited a robust and persistent neutralizing antibody and memory T-cell response in COVID-19 patients, indicating that these sustained immune responses, among most SARS-CoV-2-infected people, may play a crucial role in protection against reinfection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yan, Liu, Li, Zhou, Li, Wang, Shen, Lu, Long, Xiao, Wang, Li, Han, Yu, Zhou, Lv and Yu.)

A plug-and-play surface plasmon resonance (SPR) dual-parameter optical fiber biosensor is reported, in which Au film was firstly coated on the fiber surface for exciting SPR and the end half of the Au film was modified with Au nanoparticles to generate double SPR resonance valleys. For simultaneous detecting of glucose and cholesterol concentrations, modified P-mercaptophenylboronic acid (PMBA) and β-cyclodextrin (β-CD) were subsequently coated on the surface of sensor probe. Due to the cis-diol structure of glucose, it can interact with PMBA, leading to a red shift of one SPR resonant valley, whose maximum wavelength shift is 11.228 nm in the range of 0-1.7 mM glucose concentration. On the same time, the cholesterol molecules can realize the host-guest combination with β-CD, leading to a red shift of another SPR resonant valley, and the maximum wavelength shift is 18.893 nm in the cholesterol concentration range of 0-300 nM. The detection limits of the sensor to glucose and cholesterol are 0.00078 mM and 0.012 nM, respectively. The enhances the practical value of the dual-parameter sensor. Both theory and experiment results verify the feasibility of the "plug-and-play" sensor to measure the dual biomass of glucose and cholesterol with ultra-low detection limit and good selectivity. The proposed method provides a huge research value for the optical fiber sensor in multi-parameter measurement., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Aloe vera (L.) Burm f., which belongs to the family Aloaceae, is a perennial succulent plant and cultivated for its medicinal, cosmetic, vegetable and ornamental uses. In summer of 2021, about 15% (60 infected among 400 surveyed plants) of A. vera (A. barbadensis) plants in two gardens in Lishui, Zhejiang Province of China showed symptoms of southern blight disease. Symptomatic plants primarily exhibited slightly sunken water-soaked, dark brown lesions on taproot and basal part of the stems. As the disease progressed, leaves in the basal part of stems and subsequently the whole plant rotted and withered, with white mycelial mats occurring on infected stems and leaves. Numerous brown, spherical sclerotia were observed on the colonized tissues and soil surfaces around the infected plants. Mycelial fragments and sclerotia from symptomatic leaves were plated directly to potato dextrose agar (PDA) amended with 100 μg/ml streptomycin and incubated at 26°C in the dark. By hyphal-tip method, a total of five pure isolates were obtained from five diseased leaf samples. When cultured on PDA at 26°C for three days, colonies showed white and thick aerial mycelium, with a radial growth rate of 23.7 mm/day. Typical clamp connection structures were observed microscopically after three days and numerous globoid, rapeseed shape sclerotia, measuring 1 to 2 mm in diameter (n=50) formed after six days. These sclerotia were initially white and gradually turned dark brown with age. On the basis of morphological characteristics, the fungal isolates were identified as Athelia rolfsii (Curzi) C.C. Tu & Kimbr (anamorph Sclerotium rolfsii Sacc) (Mordue 1974). The internal transcribed spacer (ITS) and translation elongation factor 1-α gene (TEF1) regions of a representative isolate LHBJ2-4 were amplified and sequenced using the primers ITS4/ITS5 (White et al. 1990) and EF1/EF2, respectively (accession no. MZ956758 and OL365370). BLASTn search showed that the amplified ITS and TEF1 sequences had 99.71% (680/682 bp) and 99.80% (498/499 bp) identity with the A. rolfsii isolates CBS 115.22 (MH854711.1) and Sr&#95;286 (JF267815), respectively. Neighbor-joining phylogenetic tree based on the ITS sequences revealed that LHBJ2-4 clustered with A. rolfsii isolates. For pathogenicity test, three potted A. vera plants (~30 cm tall) were inoculated by placing a 0.5 cm mycelial plug of isolate LHBJ2-4 (three-day old) at the base of each A. vera plant. Three A. vera plants inoculated with sterile PDA plugs served as controls. All the inoculated plants were placed in a growth chamber at 27°C under a 12/12 h light/dark cycle. The inoculation assays were carried out twice. After 5 to 7 days, stem bases of the inoculated plants showed brown lesions that were similar to those observed in the field. However, control plants remained symptomless. Athelia rolfsii was re-isolated from all the inoculated plants and identified using morphological and molecular method described above, thus confirming Koch's postulates. Although A. rolfsii has been reported to cause disease on A. vera in India (Dubey and Pandey 2009), to the best of our knowledge, this is the first report of A. rolfsii causing southern blight on A. vera in China. Because A. rolfsii has a wide host range and is difficult to control (Punja 1985), occurrence of southern blight in China might be a serious threat for A. vera production and appropriate management strategies should be developed to control this disease.

Background and Purpose: Zuojin capsule (ZJC), a classical prescription, is outstanding in improving the conditions of patients with gastrointestinal diseases and colorectal cancer (CRC). Although ZJC has multi-ingredient and multi-target characteristics, its pharmacological effect on colorectal cancer and the underlying mechanism remain unclear., Method: Here, the activity of ZJC against CRC was evaluated by the experiments with CRC cells and HCT-116 xenografted mice. The key genes of CRC were obtained from the cancer genome atlas (TCGA). The genes potentially targeted by ZJC were collected from traditional Chinese medicine systems pharmacology (TCMSP) database. The underlying pathways related to selected targets were analyzed through gene ontology (GO) and pathway enrichment analyses. Western blot (WB), cellular thermal shift assay (CETSA), molecular docking and quantitative real-time PCR (QRT-PCR) were carried out to confirm the validity of the targets., Results: In vitro and in vivo results indicated that ZJC may inhibit CRC cells and tumor growth. The network pharmacological analysis indicated that 22 compounds, 51 targets and 20 pathways were involved in the compound-target-pathway network. Our results confirmed that ZJC inhibited cycle progression, migration and induced apoptosis by targeting candidate genes (CDKN1A, Bcl2, E2F1, PRKCB, MYC, CDK2, and MMP9). We found that ZJC could directly change the protein level by regulating the protein stability and transcriptional activity of the target., Conclusions: In summary, combined network pharmacology and biological experiments proved that the main ingredients of ZJC such as quercetin, (R)-Canadine, palmatine, rutaecarpine, evodiamine, beta-sitosterol and berberine can target CDKN1A, Bcl2, E2F1, PRKCB, MYC, CDK2 and MMP9 to combat colorectal cancer. The results of this study provide a basic theory for the clinical trials of Zuojin Capsules against colorectal cancer., (Copyright © 2021 Elsevier GmbH. All rights reserved.)

The crisis of arsenic (As) accumulation in rhizomes threatens the quality and safety of Panax notoginseng (Burk.) F.H. Chen, which is a well-known traditional Chinese herb with a long clinical history. The uptake of arsenate (AsV) could be suppressed by supplying phosphate (Pi), in which Pi transporters play important roles in the uptake of Pi and AsV. Herein, the P . notoginseng Pi transporter-encoding gene PnPht1;3 was identified and characterised under Pi deficiency and AsV exposure. In this study, the open reading frame (ORF) of PnPht1;3 was cloned according to RNA-seq and encoded 545 amino acids. The relative expression levels revealed that PnPht1;3 was significantly upregulated under phosphate deficiency and AsV exposure. Heterologous expression in Saccharomyces cerevisiae MB192 demonstrated that PnPht1;3 performed optimally in complementing the yeast Pi-transport defect and accumulated more As in the cells. Combined with the subcellular localisation prediction, it was concluded that PnPht1;3 encodes a functional plasma membrane-localised transporter protein that mediates putative high-affinity Pi/H+ symport activity and enhances the uptake of Pi and AsV. Therefore, a better understanding of the roles of the P . notoginseng Pi transporter could provide new insight for solving As accumulation in medicinal plants.

Purpose: This study aimed to investigate the feasibility, safety, and efficacy of computed tomography (CT)-guided percutaneous coaxial biopsy combined with microwave ablation (MWA) for the treatment of renal masses., Material and Methods: The clinical data of ten patients (14 tumors) treated with CT-guided percutaneous coaxial biopsy combined with MWA from January 2017 to November 2019 were retrospectively analyzed. The patients were followed up for 2-33 months. The outcomes were evaluated with plain and contrast spiral CT scans. Renal function was assessed using the estimated glomerular filtration rate., Results: No severe MWA-related complication was observed. All the tumors were successfully ablated. There was no imaging evidence of local residual tumor, local tumor recurrence, or disease progression during the follow-up period., Conclusions: CT-guided percutaneous coaxial biopsy combined with MWA might be an effective option for the diagnosis and treatment of renal masses in selected patients.

Increased glutamine metabolism by macrophages is associated with development of atherosclerotic lesions. Positron emission tomography/computed tomography (PET/CT) with a glutamine analog (2S,4 R )-4- 18 F-fluoroglutamine ( 18 F-FGln) allows quantification of glutamine consumption in vivo . Here, we investigated uptake of 18 F-FGln by atherosclerotic lesions in mice and compared the results with those obtained using the glucose analog 2-deoxy-2- 18 F-fluoro- D -glucose ( 18 F-FDG). Uptake of 18 F-FGln and 18 F-FDG by healthy control mice (C57BL/6JRj) and atherosclerotic low-density lipoprotein receptor-deficient mice expressing only apolipoprotein B100 (LDLR -/- ApoB 100/100 ) was investigated. The mice were injected intravenously with 18 F-FGln or 18 F-FDG for in vivo PET/CT imaging. After sacrifice at 70 minutes post-injection, tracer uptake was analyzed by gamma counting of excised tissues and by autoradiography of aorta cryosections, together with histological and immunohistochemical analyses. We found that myocardial uptake of 18 F-FGln was low. PET/CT detected lesions in the aortic arch, with a target-to-background ratio (SUV max , aortic arch/SUV mean , blood) of 1.95 ± 0.42 (mean ± standard deviation). Gamma counting revealed that aortic uptake of 18 F-FGln by LDLR -/- ApoB 100/100 mice (standardized uptake value [SUV], 0.35 ± 0.06) was significantly higher than that by healthy controls (0.20 ± 0.08, P = 0.03). More detailed analysis by autoradiography revealed that the plaque-to-healthy vessel wall ratio of 18 F-FGln (2.90 ± 0.42) was significantly higher than that of 18 F-FDG (1.93 ± 0.22, P = 0.004). Immunohistochemical staining confirmed that 18 F-FGln uptake in plaques co-localized with glutamine transporter SLC7A7-positive macrophages. Collectively these data show that the 18 F-FGln PET tracer detects inflamed atherosclerotic lesions. Thus, exploiting glutamine consumption using 18 F-FGln PET may have translational relevance for studying atherosclerotic inflammation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Palani, Miner, Virta, Liljenbäck, Eskola, Örd, Ravindran, Kaikkonen, Knuuti, Li, Saraste and Roivainen.)

Deep-sea hydrothermal vents are known as chemosynthetic ecosystems. However, high temperature vents emit light that hypothetically can drive photosynthesis in this habitat. Metagenomic studies have sporadically reported the occurrence of phototrophic populations such as cyanobacteria in hydrothermal vents. To determine how geographically and taxonomically widespread phototrophs are in deep-sea hydrothermal vents, we collected samples from three niches in a hydrothermal vent on the Southwest Indian Ridge and carried out an integrated metagenomic analysis. We determined the typical community structures of microorganisms found in active venting fields and identified populations of known potential chlorophototrophs and retinalophototrophs. Complete chlorophyll biosynthetic pathways were identified in all samples. By contrast, proteorhodopsins were only found in active beehive smoker diffusers. Taxonomic groups possessing potential phototrophy dependent on semiconductors present in hydrothermal vents were also found in these samples. This systematic comparative metagenomic study reveals the widespread distribution of phototrophic bacteria in hydrothermal vent fields. Our results support the hypothesis that the ocean is a seed bank of diverse microorganisms. Geothermal vent light may provide energy and confer a competitive advantage on phototrophs to proliferate in hydrothermal vent ecosystems., Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-021-00121-y., Competing Interests: Conflict of interestThere are no conflicts of interest or competing interests., (© Ocean University of China 2022.)

Objective: This retrospective study aimed to access the correlations of RENAL, PADUA and NePhRO scores with operative complications, chronic kidney disease (CKD) upstaging, and oncologic outcomes after CT-guided percutaneous Microwave Ablation (MWA) of renal tumors in order to determine their status as independent predictors of outcomes after MWA. This study also aimed to generally evaluate the efficacy of MWA in treating renal tumors., Methods: From January 2017 to December 2019, 18 patients with 27 renal tumors who had undergone simultaneous biopsy and MWA were recruited in this single-center retrospective study. Data collection included tumor characteristics, procedural protocols, complications, CKD upstaging data, local tumor control data and overall survival. All lesions were evaluated using RENAL, PADUA and NePhRO scores, and further analysis was performed to determine whether the scores were correlated with operative complications, CKD upstaging, local tumor control and overall survival., Results: The minor and major complication rates were 16.7% and 0%, respectively. Two patients with solitary kidney experienced CKD upstaging. Local tumor recurrence was identified in one type of tumor (3.7%) in the first year of follow-up. L. parameter (P = .031), longitudinal (polar) location score (P = .011), Ne. parameter (P = .036), number of kidneys (P = .005), and number of lesions (P = .008), were predictive factors significantly associated with the occurrence of complications. Besides, CKD upstaging was associated with A. parameter (P = .032) and urinary collecting system score (P = .028). RENAL, PADUA, and NePhRO scores were significantly correlated with complications, overall survival, and CKD upstaging, respectively (P < .05)., Conclusion: CT-guided percutaneous MWA was found to be a valuable alternative in the treatment of renal tumors for selected patients. Furthermore, RENAL, PADUA and NePhRO scores were not independent predictors of outcomes of MWA.

Objective: To explore the performance of a deep learning algorithm that combined multi-view fusion with active contour constrained for ossicles segmentation on the 10 μm otology CT images. Methods: The 10 μm otology CT image data from 79 cases (56 cases were from volunteers and 23 cases were from specimens) were retrospectively collected in the Radiology Department of Beijing Friendship Hospital from October 2019 to December 2020. An annotation of malleus, incus, and stapes were conducted. Then the datasets were established and were divided into training set ( n =55), validation set ( n =8), and test set ( n =16). Using the rapid localization of the region of interest combined with the precise segmentation algorithm, the malleus, incus and stapes were segmented and fused from three perspectives of coronal, sagittal and cross-sectional views. Besides, an active contour loss was designed simultaneously for the segmentation of stapes. Dice similarity coefficient (DSC) was used as the objective evaluation metric for the evaluation of the segmentation results. The inter group DSC of the proposed method was compared with that of the basic method and other methods. Results: The average DSC values of the multi-view fusion segmentation algorithm for malleus, incus and stapes reached up to 94.2%±2.7%, 94.6%±2.6% and 76.0%±5.5%, respectively. After adopting the constraint of active contour loss method, the average DSC of stapes was improved (76.4%±5.4% vs 76.0%±5.5%). The visualization results also demonstrated that the segmentation results of the stapes were more complete. Conclusions: Multi-view fusion algorithm based on 10 μm otology CT images can realize accurate segmentation of malleus and incus. Combined with the constraint of active contour loss method, the segmentation accuracy of stapes can be further improved.

The 68 Gallium-labeled 1,4,7-triazacyclononane-1-glutaric acid-4,7-diacetic acid conjugated radiolabelled arginine-glycine-aspartic acid peptide ([ 68 Ga]Ga-NODAGA-RGD) is a positron emission tomography (PET) tracer binding to cell surface receptor α v β 3 integrin that is upregulated during angiogenesis and inflammation. We studied whether α v β 3 targeting PET imaging can detect myocardial inflammation in a rat model of autoimmune myocarditis. To induce myocarditis, rats ( n = 8) were immunized with porcine cardiac myosin in complete Freund's adjuvant on days 0 and 7. Control rats ( n = 8) received Freund's adjuvant alone. On day 21, in vivo PET/CT imaging with [ 68 Ga]Ga-NODAGA-RGD followed by ex vivo autoradiography and immunohistochemistry were carried out. Inflammatory lesions were detected histologically in the myocardium of 7 out of 8 immunized rats. In vivo PET images showed higher [ 68 Ga]Ga-NODAGA-RGD accumulation in the myocardium of rats with inflammation than the non-inflamed myocardium of control rats (SUV mean 0.4 ± 0.1 vs. 0.1 ± 0.02; P = 0.00006). Ex vivo autoradiography and histology confirmed that [ 68 Ga]Ga-NODAGA-RGD uptake co-localized with inflammatory lesions containing α v β 3 integrin-positive capillary-like structures. A non-specific [ 68 Ga]Ga-DOTA-(RGE) 2 tracer showed 76% lower uptake than [ 68 Ga]Ga-NODAGA-RGD in the inflamed myocardium. Our results indicate that α v β 3 integrin-targeting [ 68 Ga]Ga-NODAGA-RGD is a potential PET tracer for the specific detection of active inflammatory lesions in autoimmune myocarditis., Competing Interests: AS received consultancy or speaker fees from Amgen, Astra Zeneca, Boehringer Ingelheim, Abbott, and Bayer not related to the present study. JK received consultancy fees from GE Healthcare and AstraZeneca and speaker fees from GE Healthcare, Bayer, and Lundbeck. Boehringer-Ingelheim and Merck, outside of the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Jahandideh, Ståhle, Virta, Li, Liljenbäck, Moisio, Knuuti, Roivainen and Saraste.)

Purpose: To evaluate the short-term efficacy and safety of immunotherapy with sintilimab combined with bronchial arterial infusion (BAI) chemotherapy/drug-eluting embolic (DEE) bronchial arterial chemoembolization (BACE) for advanced non-small cell lung cancer (NSCLC)., Materials and Methods: Ten patients with advanced NSCLC were treated with sintilimab plus BAI/DEE-BACE between December 2019 and November 2020 and retrospectively evaluated. The Response Evaluation Criteria in Solid Tumors version 1.1 was applied to evaluate the treatment response. The local tumor control duration, progression-free survival (PFS), and overall survival (OS) were estimated using the Kaplan-Meier analysis., Results: At 30 days after the last multimodal treatment, complete response, partial response, and stable disease were recorded in 1 (10%), 7 (70%), and 2 (20%) patients, respectively, for an objective response rate of 80% and a disease control rate of 100%. No patient experienced progressive disease. The median duration of local tumor control was 8.0 months (95% CI, 6.2-9.7 months). The median PFS and OS were 11.0 months (95% CI, 6.9-15.1 months) and 8.0 months (95% CI, 5.5-10.5 months), respectively. Two cases of Grade III adverse events related to medications were reported., Conclusions: Sintilimab combined with BAI/DEE-BACE for patients with advanced NSCLC appears to be safe and feasible. Compared with previous studies on BAI/DEE-BACE, the addition of immunotherapy may improve survival., (Copyright © 2021 SIR. Published by Elsevier Inc. All rights reserved.)

Mare volcanics on the Moon are the key record of thermo-chemical evolution throughout most of lunar history 1-3 . Young mare basalts-mainly distributed in a region rich in potassium, rare-earth elements and phosphorus (KREEP) in Oceanus Procellarum, called the Procellarum KREEP Terrane (PKT) 4 -were thought to be formed from KREEP-rich sources at depth 5-7 . However, this hypothesis has not been tested with young basalts from the PKT. Here we present a petrological and geochemical study of the basalt clasts from the PKT returned by the Chang'e-5 mission 8 . These two-billion-year-old basalts are the youngest lunar samples reported so far 9 . Bulk rock compositions have moderate titanium and high iron contents  with KREEP-like rare-earth-element and high thorium concentrations. However, strontium-neodymium isotopes indicate that these basalts were derived from a non-KREEP mantle source. To produce the high abundances of rare-earth elements and thorium, low-degree partial melting and extensive fractional crystallization are required. Our results indicate that the KREEP association may not be a prerequisite for young mare volcanism. Absolving the need to invoke heat-producing elements in their source implies a more sustained cooling history of the lunar interior to generate the Moon's youngest melts., (© 2021. The Author(s).)

Objective: To explore the serum cyclic polypeptide biomarkers for ovarian cancer diagnosis. Methods: A total of 54 patients with epithelial ovarian cancer confirmed by pathology in Cancer Hospital, Chinese Academy of Medical Sciences from March 2018 to September 2018 were selected as the study subjects, and 40 healthy women with normal examination results in the cancer screening center were selected as the control. All of the samples were randomly divided into training set and validation set at the ratio of 1∶1 with a random number. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) combined with magnetic bead technology was used for detecting peptide profiling in serum samples to screen significantly differently expressed peptides between ovarian cancer group and control group of the training set (score>5). Receiver operating characteristic (ROC) curve analysis was used to screen differential peptide peaks with area under curve (AUC) ≥0.8, sensitivity and specificity>90% in the training set and validation set. Liquid chromatography-mass spectrometry (LC-MS/MS) was further used to determine the composition of differentially expressed peptides. Results: By comparing the peptide profiles of the two groups, 102 differential peptide peaks were initially detected in the mass-to-charge ratio range of 1 000 to 10 000. ROC curve analysis showed that there were 42 differential peptide peaks with AUC ≥0.8 in both training set and validation set, 19 of which were highly expressed in ovarian cancer group, and 23 were lowly expressed. There were 15 different peptide peaks in highly expressed ovarian cancer group with sensitivity and specificity over 90%. The mass-to-charge ratios were 7 744.27, 5 913.41, 5 329.87, 4 634.21, 4 202.02, 3 879.26, 3 273.35, 3 253.79, 3 234.34, 2 950.33, 2 664.51, 2 018.38, 1 893.37, 1 498.69 and 1 287.55. There were 15 different peptide peaks in lowly expressed ovarian cancer group with sensitivity and specificity over 90%, the mass-to-charge ratios were 9 288.46, 7 759.77, 5 925.24, 4 652.77, 4 210.42, 3 887.02, 3 279.90, 3 240.82, 2 962.15, 2 932.70, 2 022.42, 1 897.16, 1 501.69, 1 337.38 and 1 290.13. No protein composition was identified in 15 different peptide peaks in lowly expressed ovarian cancer group. The two protein compositions identified in 15 different peptide peaks in highly expressed ovarian cancer group were recombinant serglycin (SRGN) and fibinogen alpha chain (FGA), the mass-to-charge ratios of which were 1 498.696 and 5 913.417, respectively. The sensitivity and specificity of the two proteins for ovarian cancer diagnosis were 100%, 100% and 90.9%, 100%, respectively. Conclusion: SRGN and FGA are highly expressed in the serum of ovarian cancer patients, which may be potential diagnostic markers for ovarian cancer.

Thermoelectric properties of CoSb 3 -based skutterudites are greatly determined by the removal of detrimental impurities, such as (Fe/Co)Sb 2 , (Fe/Co)Sb, and Sb. In this study, we use a facile temperature gradient zone melting (TGZM) method to synthesize high-performance CoSb 3 -based skutterudites by impurity removal. After removing metallic or semimetallic impurities (Fe/Co)Sb, (Fe/Co)Sb 2 , and Sb, the carrier concentration of TGZM-Ce 0.75 Fe 3 CoSb 12 can be reduced to 1.21 × 10 20 cm -3 and the electronic thermal conductivity dramatically reduced to 0.7 W m -1 K -1 at 693 K. Additionally, removing these impurities also effectively reduces the lattice thermal conductivity from 7.2 W m -1 K -1 of cast-Ce 0.75 Fe 3 CoSb 12 to 1.02 W m -1 K -1 of TGZM-Ce 0.75 Fe 3 CoSb 12 at 693 K. As a consequence, TGZM-Ce 0.75 Fe 3 CoSb 12 approaches a high power factor of 11.7 μW cm -1 K -2 and low thermal conductivity of 1.72 W m -1 K -1 at 693 K, leading to a peak zT of 0.48 at 693 K, which is 10 times higher than that of cast-Ce 0.75 Fe 3 CoSb 12 . This study indicates that our facile TGZM method can effectively synthesize high-performance CoSb 3 -based skutterudites by impurity removal and set up a solid foundation for further development.

CoSb 3 -based skutterudite is a promising mid-temperature thermoelectric material. However, the high lattice thermal conductivity limits its further application. Filling is one of the most effective methods to reduce the lattice thermal conductivity. In this study, we investigate the Ce filling limit and its influence on thermoelectric properties of p-type Fe 3 CoSb 12 -based skutterudites grown by a temperature gradient zone melting (TGZM) method. Crystal structure and composition characterization suggests that a maximum filling fraction of Ce reaches 0.73 in a composition of Ce 0.73 Fe 2.73 Co 1.18 Sb 12 prepared by the TGZM method. The Ce filling reduces the carrier concentration to 1.03 × 10 20 cm -3 in the Ce 1.25 Fe 3 CoSb 12 , leading to an increased Seebeck coefficient. Density functional theory (DFT) calculation indicates that the Ce-filling introduces an impurity level near the Fermi level. Moreover, the rattling effect of the Ce fillers strengthens the short-wavelength phonon scattering and reduces the lattice thermal conductivity to 0.91 W m -1 K -1 . These effects induce a maximum Seebeck coefficient of 168 μV K -1 and a lowest κ of 1.52 W m -1 K - 1 at 693 K in the Ce 1.25 Fe 3 CoSb 12 , leading to a peak zT value of 0.65, which is 9 times higher than that of the unfilled Fe 3 CoSb 12 .

Genomic alterations are crucial for the development and progression of human cancers. Copy-number gains found in genes encoding metabolic enzymes may induce triple-negative breast cancer (TNBC) adaptation. However, little is known about how metabolic enzymes regulate TNBC metastasis. Using our previously constructed multiomic profiling of a TNBC cohort, we identified decaprenyl diphosphate synthase subunit 1 (PDSS1) as an essential gene for TNBC metastasis. PDSS1 expression was significantly upregulated in TNBC tissues compared with adjacent normal tissues and was positively associated with poor survival among patients with TNBC. PDSS1 knockdown inhibited TNBC cell migration, invasion, and distant metastasis. Mechanistically, PDSS1, but not a catalytically inactive mutant, positively regulated the cellular level of coenzyme Q10 (CoQ10) and intracellular calcium levels, thereby inducing CAMK2A phosphorylation, which is essential for STAT3 phosphorylation in the cytoplasm. Phosphorylated STAT3 entered the nucleus, promoting oncogenic STAT3 signaling and TNBC metastasis. STAT3 phosphorylation inhibitors (e.g., Stattic) effectively blocked PDSS1-induced cell migration and invasion in vitro and tumor metastasis in vivo . Taken together, our study highlights the importance of targeting the previously uncharacterized PDSS1/CAMK2A/STAT3 oncogenic signaling axis, expanding the repertoire of precision medicine in TNBC. SIGNIFICANCE: A novel metabolic gene PDSS1 is highly expressed in triple-negative breast cancer tissues and contributes to metastasis, serving as a potential therapeutic target for combating metastatic disease., (©2021 American Association for Cancer Research.)

A novel moderately thermophilic, anaerobic, heterotrophic bacterium (strain SY095 T ) was isolated from a hydrothermal vent chimney located on the Southwest Indian Ridge at a depth of 2730 m. Cells were Gram-stain-positive, motile, straight to slightly curved rods forming terminal endospores. SY095 T was grown at 45-60 °C (optimum 50-55 °C), pH 6.0-7.5 (optimum 7.0), and in a salinity of 1-4.5 % (w/v) NaCl (optimum 2.5 %). Substrates utilized by SY095 T included fructose, glucose, maltose, N -acetyl glucosamine and tryptone. Casamino acid and amino acids (glutamate, glutamine, lysine, methionine, serine and histidine) were also utilized. The main end products from glucose fermentation were acetate, H 2 and CO 2 . Elemental sulphur, sulphate, thiosulphate, sulphite, fumarate, nitrate, nitrite and Fe(III) were not used as terminal electron acceptors. The predominant cellular fatty acids were C 14 : 0 (60.5%) and C 16 : 0 (7.6 %). The main polar lipids consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, five unidentified phospholipids and two unidentified aminophospholipids. No respiratory quinones were detected. The chromosomal DNA G+C content was 30.8 mol%. The results of phylogenetic analysis of the 16S rRNA gene sequences indicated that SY095 T was closely related to Crassaminicella profunda Ra1766H T (95.8 % 16S rRNA gene sequence identity). SY095 T exhibited 78.1 % average nucleotide identity (ANI) to C. profunda Ra1766H T . The in silico DNA-DNA hybridization (DDH) value indicated that SY095 T shared 22.7 % DNA relatedness with C. profunda Ra1766H T . On the basis of its phenotypic, genotypic and phylogenetic characteristics, SY095 T is suggested to represent a novel species of the genus Crassaminicella , for which the name Crassaminicella thermophila sp. nov. is proposed. The type strain is SY095 T (=JCM 34213=MCCC 1K04191). An emended description of the genus Crassaminicella is also proposed.

Savin juniper is an excellent species for desertification control in arid and semi-arid areas, where it typically establishes under the protection of nurse plants. Ultimately, established plants emerge into full light as they grow, and this transition is accompanied by an increase in the preponderance of scale-like versus needle-like leaf forms. To test how age and variable light environments affect shade tolerance in savin juniper, we established a pot study under field conditions, with two age cohorts (1- and 4-year-old rooted scions) and three light regimes (10%, 50% and 100% light transmittance). We measured growth, leaf parameters, photosynthesis, chlorophyll fluorescence and foliar pigments on a monthly basis (seven growing months per year, from 2015 to 2017). Overall, there was little interaction among all variables, and both cohort and light regime had significant effects. Leaf form and spacing varied continuously, tending towards shorter, more closely spaced and more appressed scale leaves with higher dry leaf mass per area in older plants or under higher light. There were no clear age-related patterns in carotenoids but both cohort and light had significant effects on gas exchange and chlorophyll fluorescence variables. We conclude that savin juniper shows an intermediate tolerance to shade that changes with growth in that younger plants were less tolerant of full sun than older plants, consistent with its reliance on nurse plants for ultimate establishment in the open., (© 2021 German Society for Plant Sciences and The Royal Botanical Society of the Netherlands.)

Background: Few studies have discussed the contradictory roles of mutated-PI3Kα in HER2-positive (HER2+) breast cancer. Thus, we characterised the adaptive roles of PI3Kα mutations among HER2+ tumour progression., Methods: We conducted prospective clinical sequencing of 1923 Chinese breast cancer patients and illustrated the clinical significance of PIK3CA mutations in locally advanced and advanced HER2+ cohort. A high-throughput PIK3CA mutations-barcoding screen was performed to reveal impactful mutation sites in tumour growth and drug responses., Results: PIK3CA mutations acted as a protective factor in treatment-naïve patients; however, advanced/locally advanced patients harbouring mutated-PI3Kα exhibited a higher progressive disease rate (100% vs. 15%, p = .000053) and a lower objective response rate (81.7% vs. 95.4%, p = .0008) in response to trastuzumab-based therapy. Meanwhile, patients exhibiting anti-HER2 resistance had a relatively high variant allele fraction (VAF) of PIK3CA mutations; we defined the VAF > 12.23% as a predictor of poor anti-HER2 neoadjuvant treatment efficacy. Pooled mutations screen revealed that specific PI3Kα mutation alleles mediated own biological effects. PIK3CA functional mutations suppressed the growth of HER2+ cells, but conferred anti-HER2 resistance, which can be reversed by the PI3Kα-specific inhibitor BYL719., Conclusions: We proposed adaptive treatment strategies that the mutated PIK3CA and amplified ERBB2 should be concomitantly inhibited when exposing to continuous anti-HER2 therapy, while the combination of anti-HER2 and anti-PI3Kα treatment was not essential for anti-HER2 treatment-naïve patients. These findings improve the understanding of genomics-guided treatment in the different progressions of HER2+ breast cancer., (© 2021 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Background: Colorectal cancer (CRC) is the third most common tumor worldwide. Aberrant N6-methyladenosine (m6A) modification can influence the progress of the CRC. Additionally, long noncoding RNA (lncRNA) plays a critical role in CRC and has a close relationship with m6A modification. However, the prognostic potential of m6A-related lncRNAs in CRC patients still remains to be clarified., Methods: We use "limma" R package, "glmnet" R package, and "survival" R package to screen m6A-related-lncRNAs with prognostic potential. Then, we comprehensively analysed and integrated the related lncRNAs in different TNM stages from TCGA database using the LASSO Cox regression. Meanwhile, the relationship between functional enrichment of m6A-related lncRNAs and immune microenvironment in CRC was also investigated using the TCGA database. A prognostic model was constructed and validated to determine the association between m6A-related lncRNAs in different TNM stages and the prognosis of CRC., Result: We demonstrated that three related m6A lncRNAs in different TNM stages were associated with the prognosis of CRC patients. Patients from the TCGA database were classified into the low-risk and the high-risk groups based on the expression of these lncRNAs. The patients in the low-risk group had longer overall survival than the patients in the high-risk group ( P < 0.001). We further constructed and validated a prognostic nomogram based on these genes with a C-index of 0.80. The receiver operating characteristic curves confirmed the predictive capacity of the model. Meanwhile, we also found that the low-risk group has the correlation with the dendritic cell (DC). Finally, we discovered the relationship between the m6A regulators and the three lncRNAs., Conclusion: The prognostic model based on three m6A-related lncRNAs exhibits superior predictive performance, providing a novel prognostic model for the clinical evaluation of CRC patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhan Zhao et al.)

Recent machine learning models for bandgap prediction that explicitly encode the structure information to the model feature set significantly improve the model accuracy compared to both traditional machine learning and non-graph-based deep learning methods. The ongoing rapid growth of open-access bandgap databases can benefit such model construction not only by expanding their domain of applicability but also by requiring constant updating of the model. Here, we build a new state-of-the-art multi-fidelity graph network model for bandgap prediction of crystalline compounds from a large bandgap database of experimental and density functional theory (DFT) computed bandgaps with over 806 600 entries (1500 experimental, 775 700 low-fidelity DFT, and 29 400 high-fidelity DFT). The model predicts bandgaps with a 0.23 eV mean absolute error in cross validation for high-fidelity data, and including the mixed data from all different fidelities improves the prediction of the high-fidelity data. The prediction error is smaller for high-symmetry crystals than for low symmetry crystals. Our data are published through a new cloud-based computing environment, called the "Foundry," which supports easy creation and revision of standardized data structures and will enable cloud accessible containerized models, allowing for continuous model development and data accumulation in the future.

Purpose: The three positron emission tomography (PET) imaging compounds: (2 S ,4 R )-4-[ 18 F]Fluoroglutamine ([ 18 F]FGln), L -[methyl- 11 C]Methionine ([ 11 C]Met), and 2-deoxy-2-[ 18 F]fluoro- D -glucose ([ 18 F]FDG) were investigated to contrast their ability to image orthotopic BT4C gliomas in BDIX rats. Two separate small animal imaging systems were compared for their tumor detection potential. Dynamic acquisition of [ 18 F]FGln was evaluated with multiple pharmacokinetic models for future quantitative comparison., Procedures: Up to four imaging studies were performed on each orthotopically grafted BT4C glioma-bearing BDIX rat subject (n = 16) on four consecutive days. First, a DOTAREM ® contrast enhanced MRI followed by attenuation correction CT and dynamic PET imaging with each radiopharmaceutical (20 min [ 11 C]Met, 60 min [ 18 F]FDG, and 60 min [ 18 F]FGln with either the Molecubes PET/CT (n = 5) or Inveon PET/CT cameras (n = 11). Ex vivo brain autoradiography was completed for each radiopharmaceutical and [ 18 F]FGln pharmacokinetics were studied by injecting 40 MBq into healthy BDIX rats (n = 10) and collecting blood samples between 5 and 60 min. Erythrocyte uptake, plasma protein binding and plasma parent-fraction were combined to estimate the total blood bioavailability of [ 18 F]FGln over time. The corrected PET-image blood data was then applied to multiple pharmacokinetic models., Results: Average BT4C tumor-to-healthy brain tissue uptake ratios (TBR) for PET images reached maxima of: [ 18 F]FGln TBR: 1.99 ± 0.19 (n = 13), [ 18 F]FDG TBR: 1.41 ± 0.11 (n = 6), and [ 11 C]Met TBR: 1.08 ± 0.08, (n = 12) for the dynamic PET images. Pharmacokinetic modeling in dynamic [ 18 F]FGln studies suggested both reversible and irreversible uptake play a similar role. Imaging with Inveon and Molecubes yielded similar end-result ratios with insignificant differences (p > 0.25)., Conclusions: In orthotopic BT4C gliomas, [ 18 F]FGln may offer improved imaging versus [ 11 C]Met and [ 18 F]FDG. No significant difference in normalized end-result data was found between the Inveon and Molecubes camera systems. Kinetic modelling of [ 18 F]FGln uptake suggests that both reversible and irreversible uptake play an important role in BDIX rat pharmacokinetics., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Miner, Liljenbäck, Virta, Helin, Eskola, Elo, Teuho, Seppälä, Oikonen, Yang, Kindler-Röhrborn, Minn, Li and Roivainen.)

Background: Investigations of the pathogenic mechanisms in motor neurons (MNs) derived from amyotrophic lateral sclerosis (ALS) disease-specific induced pluripotent stem (iPS) cell lines could improve understanding of the issues affecting MNs. Therefore, in this study we explored mutant superoxide dismutase 1 (SOD1) protein expression in MNs derived from the iPS cell lines of ALS patients carrying different SOD1 mutations., Methods: We generated induced pluripotent stem cell (iPSC) lines from two familial ALS (FALS) patients with SOD1-V14M and SOD1-C111Y mutations, and then differentiated them into MNs. We investigated levels of the SOD1 protein in iPSCs and MNs, the intracellular Ca2+ levels in MNs, and the lactate dehydrogenase (LDH) activity in the process of differentiation into the MNs derived from the controls and ALS patients' iPSCs., Results: The iPSCs from the two FALS patients were capable of differentiation into MNs carrying different SOD1 mutations and differentially expressed MN markers. We detected high SOD1 protein expression and high intracellular calcium levels in both the MN and iPSCs that were derived from the two SOD1 mutant patients. However, at no time did we observe stronger LDH activity in the patient lines compared with the control lines., Conclusions: MNs derived from patient-specific iPSC lines can recapitulate key aspects of ALS pathogenesis, providing a cell-based disease model to further elucidate disease pathogenesis and explore gene repair coupled with cell-replacement therapy. Incremental mutant expressions of SOD1 in MNs may have disrupted MN function, either causing or contributing to the intracellular calcium disturbances, which could lead to the occurrence and development of the disease., (Copyright © 2021 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Background: The aim of the study was to explore the outcomes of computed tomography-guided microwave ablation (MWA) in non-small cell lung cancer (NSCLC) patients with adjacent lobe invasion (ALI), and to compare the outcomes of ALI-NSCLC and non-ALI NSCLC patients after MWA., Methods: A total of 319 NSCLC patients and 366 tumors treated with MWA were included in the study, comprising 34 ALI-NSCLC patients and 285 non-ALI NSCLC patients. Complications, local recurrence rates, progression-free survival (PFS), and overall survival (OS) were compared. Logistic regression analyses were used to investigate the correlation between ALI and the occurrence of pneumothorax after MWA., Results: The mean tumor diameter of ablated tumors was 3.6 ± 2.2 cm. There were 95 (29.8%) NSCLC patients in which pneumothorax occurred after MWA, and all patients recovered. Of these, the ALI group had a significantly higher incidence rate of pneumothorax than the non-ALI group (52.9% vs. 27.0%, p = 0.002). The median PFS and OS for the ALI group were 12.0 ± 10.2 and 15.5 ± 9.5 months, respectively, and that of the non-ALI group were 13.0 ± 10.6 and 17.0 ± 11.1 months, respectively, and no significant difference was found in PFS (p = 0.329) nor OS (p = 0.394) between the two groups. Local recurrence rates for ALI and non-ALI groups were 29.4% and 20.7%, respectively, and no significant difference was found (p = 0.244). Logistic regression analyses revealed that ALI can increase the risk of pneumothorax (hazard ratio [HR], 2.867; p = 0.012)., Conclusions: MWA is an effective and safe approach for ALI-NSCLC treatment. Although ALI can increase the risk of pneumothorax, ALI-NSCLC patients reveal a comparable outcome to non-ALI NSCLC patients after MWA., (© 2021 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Despite the unequivocal success of hematopoietic stem and progenitor cell gene therapy, limitations still exist including genotoxicity and variegation/silencing of transgene expression. A class of DNA regulatory elements known as chromatin insulators (CIs) can mitigate both vector transcriptional silencing (barrier CIs) and vector-induced genotoxicity (enhancer-blocking CIs) and have been proposed as genetic modulators to minimize unwanted vector/genome interactions. Recently, a number of human, small-sized, and compact CIs bearing strong enhancer-blocking activity were identified. To ultimately uncover an ideal CI with a dual, enhancer-blocking and barrier activity, we interrogated these elements in vitro and in vivo . After initial screening of a series of these enhancer-blocking insulators for potential barrier activity, we identified three distinct categories with no, partial, or full protection against transgene silencing. Subsequently, the two CIs with full barrier activity (B4 and C1) were tested for their ability to protect against position effects in primary cells, after incorporation into lentiviral vectors (LVs) and transduction of human CD34 + cells. B4 and C1 did not adversely affect vector titers due to their small size, while they performed as strong barrier insulators in CD34 + cells, both in vitro and in vivo , shielding transgene's long-term expression, more robustly when placed in the forward orientation. Overall, the incorporation of these dual-functioning elements into therapeutic viral vectors will potentially provide a new generation of safer and more efficient LVs for all hematopoietic stem cell gene therapy applications.

Background: Tiller number is a factor determining panicle number and grain yield in wheat (Triticum aestivum). Auxin plays an important role in the regulation of branch production. PIN-FORMED 1 (PIN1), an auxin efflux carrier, plays a role in the regulation of tiller number in rice (Oryza sativa); however, little is known on the roles of PIN1 in wheat., Results: Nine homologs of TaPIN1 genes were identified in wheat, of which TaPIN1-6 genes showed higher expression in the stem apex and young leaf in wheat, and the TaPIN1-6a protein was localized in the plasma membrane. The down-expression of TaPIN1s increased the tiller number in TaPIN1-RNA interference (TaPIN1-RNAi) transgenic wheat plants, indicating that auxin might mediate the axillary bud production. By contrast, the spikelet number, grain number per panicle, and the 1000-grain weight were decreased in the TaPIN1-RNAi transgenic wheat plants compared with those in the wild type. In summary, a reduction of TaPIN1s expression increased the tiller number and grain yield per plant of wheat., Conclusions: Phylogenetic analysis and protein structure of nine TaPIN1 proteins were analyzed, and subcellular localization of TaPIN1-6a was located in the plasma membrane. Knock-down expression of TaPIN1 genes increased the tiller number of transgenic wheat lines. Our study suggests that TaPIN1s is required for the regulation of grain yield in wheat., (© 2021. The Author(s).)

Purely organic room-temperature phosphorescence endowing very fast intersystem crossing from through-space systems has not been well investigated. Here we report three space-confined bridged phosphors, where phenothiazine is linked with dibenzothiophene, dibenzofuran, and carbazole by a 9,9-dimethylxanthene bridge. Nearly pure phosphorescence is observed in the crystals at room temperature. Interestingly, phosphorescence comes solely from the phenothiazine segment. Experimental results indicate that bridged counterparts of dibenzothiophene, dibenzofuran, and carbazole contribute as close-lying triplet states with locally excited (LE) character. The through-space spin-orbit coupling principle is proposed in these bridged systems, as their 1 LE and 3 LE states have intrinsic spatial overlap, degenerate energy levels, and tilting face-to-face alignment. The resulting effective through-space spin-orbit coupling leads to efficient intersystem crossing a with rate constant as high as 10 9 s -1 and an overwhelming triplet decay channel of the singlet excited state., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Hypoxia and angiogenesis play key roles in the pathogenesis of esophageal squamous cell carcinoma (ESCC), but regulators linking these two pathways to drive tumor progression remain elusive. Here we provide evidence of ADAM9's novel function in ESCC progression. Increasing expression of ADAM9 was correlated with poor clinical outcomes in ESCC patients. Suppression of ADAM9 function diminished ESCC cell migration and in vivo metastasis in ESCC xenograft mouse models. Using cellular fractionation and imaging, we found a fraction of ADAM9 was present in the nucleus and was uniquely associated with gene loci known to be linked to the angiogenesis pathway demonstrated by genome-wide ChIP-seq. Mechanistically, nuclear ADAM9, triggered by hypoxia-induced translocation, functions as a transcriptional repressor by binding to promoters of genes involved in the negative regulation of angiogenesis, and thereby promotes tumor angiogenesis in plasminogen/plasmin pathway. Moreover, ADAM9 suppresses plasminogen activator inhibitor-1 gene transcription by interacting with its transcription factors at the promoter. Our findings uncover a novel regulatory mechanism of ADAM9 as a transcriptional regulator in angiogenesis and highlight ADAM9 as a promising therapeutic target for ESCC treatment., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Zizania latifolia is a perennial plant native to East Asia. The swollen culm of Z. latifolia is a popular vegetable and traditional herbal medicine consumed in China and some other Asian countries. From 2019 to 2021, a sheath rot disease was found in Zhejiang Province of China. Symptoms mainly occurred in the leaf sheath showing as brown necrotic lesions surrounded by yellow halos. The pathogen fungal isolates were isolated from the affected sheaths. Ten representative isolates were selected for morphological and molecular identification by phylogenetic analyses of the translation elongation factor 1-α ( TEF1 ) and the RNA polymerase II subunit beta ( RPB2 ) gene regions. Based on the combined datasets, the fungal isolates were identified as Fusarium andiyazi . Koch's postulates were confirmed by pathogenicity test, re-isolation and re-identification of the fungal isolates. To the best of our knowledge, this is the first report of sheath rot caused by F. andiyazi in Z. latifolia in China.

Background: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder associated with loss of motor neurons. Our objective was to explore the epidemiology, clinical features, and survival factors of 1809 patients with ALS., Methods: We analyzed 1809 ALS patients, who were recruited from the Peking University Third Hospital from January 2005 to December 2015. Demographic data and disease-related parameters were collected. Kaplan-Meier curves were used to compare survival time. Cox proportional hazards function and the hazard ratio were used to identify adjusted prognostic predictors., Results: The results showed that the average annual incidence in Beijing alone was 0.38 cases/100,000 person-years and the mean age of onset was 48.88 ± 11.35 (95% confidence interval [CI]: 48.17-49.85) years. The median survival time from onset to death/tracheostomy was 58.89 ± 33.03 (95% CI: 51.46-63.84) months. In the adjusted Cox proportional hazard model, age of onset, diagnosis delay, rate of disease progression (Amyotrophic Lateral Sclerosis Functional Rating Scale Revised decline [points/month]), and body mass index all had an independent effect on survival in ALS., Conclusions: Our study provides information on epidemiology, clinical features, and survival factors of patients with ALS in China. These results can be helpful in clinical practice, clinical trial design, and validation of new tools to predict disease progression., (Copyright © 2021 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)