Specific Decrease in B-Cell-Derived Extracellular Vesicles Enhances Post-Chemotherapeutic CD8+ T Cell Responses.

Systemic immunosuppression greatly affects the chemotherapeutic antitumor effect. Here, we showed that CD19+ extracellular vesicles (EVs) from B cells through CD39 and CD73 vesicle-incorporated proteins hydrolyzed ATP from chemotherapy-treated tumor cells into adenosine, thus impairing CD8+ T cell responses. Serum CD19+ EVs were increased in tumor-bearing mice and patients. Patients with fewer serum CD19+ EVs had a better prognosis after chemotherapy. Upregulated hypoxia-inducible factor-1α (HIF-1α) promoted B cells to release CD19+ EVs by inducing Rab27a mRNA transcription. Rab27a or HIF-1α deficiency in B cells inhibited CD19+ EV production and improved the chemotherapeutic antitumor effect. Silencing of Rab27a in B cells by inactivated Epstein-Barr viruses carrying Rab27a siRNA greatly improved chemotherapeutic efficacy in humanized immunocompromised NOD PrkdcscidIl2rg-/- mice. Thus, decreasing CD19+ EVs holds high potential to improve the chemotherapeutic antitumor effect.

Dissecting the molecular mechanism of russeting in sand pear (Pyrus pyrifolia Nakai) by metabolomics, transcriptomics, and proteomics.

Brown coloration and a rough appearance as russet and semi-russet (partial russet) are features unique to the popular Asian sand pear (Pyrus pyrifolia Nakai). The degree of russeting is different between different genotypes. Russeting is sensitive to water fluctuations, where excessive rainwater can trigger/stimulate its development. However, the molecular mechanism of russeting is currently unclear. Here, we employed multi-omics, i.e., metabolomics, transcriptomics, and proteomics, and analyzed the effect of different sand pear genotypes and artificial rainfall on russeting of pear fruits. This led to the identification of 79, 64, and 29 differentially produced/expressed metabolites, transcripts, and proteins that are involved in the biosynthesis of suberin, phenylpropane, cutin, and waxes. Further analysis of these differentially expressed genes and their encoded proteins revealed that four of them exhibited high expression at both transcript and protein levels. Transient expression of one such gene, PbHHT1 (accession number 103966555), which encodes ω-hydroxypalmitate-O-feruloyl transferase, in young green non-russet fruits triggered premature suberization in the russeting pear genotypes. This coincided with increased production of 16-feruloyloxypalmitic acid, a conjugated compound between phenols and esters during the polymerization for suberin formation. Collectively, our data from the combined three omics demonstrate that russeting in sand pear is a complex process involving the biosynthesis and transport of suberin and many other secondary metabolites.

An RTM-GWAS procedure reveals the QTL alleles and candidate genes for three yield-related traits in upland cotton.

BACKGROUND: Cotton (Gossypium spp.) fiber yield is one of the key target traits, and improved fiber yield has always been thought of as an important objective in the breeding programs and production. Although some studies had been reported for the understanding of genetic bases for cotton yield-related traits, the detected quantitative trait loci (QTL) for the traits is still very limited. To uncover the whole-genome QTL controlling three yield-related traits in upland cotton (Gossypium hirsutum L.), phenotypic traits were investigated under four planting environments and 9244 single-nucleotide polymorphism linkage disequilibrium block (SNPLDB) markers were developed in an association panel consisting of 315 accessions. RESULTS: A total of 53, 70 and 68 significant SNPLDB loci associated with boll number (BN), boll weight (BW) and lint percentage (LP), were respectively detected through a restricted two-stage multi-locus multi-allele genome-wide association study (RTM-GWAS) procedure in multiple environments. The haplotype/allele effects of the significant SNPLDB loci were estimated and the QTL-allele matrices were organized for offering the abbreviated genetic composition of the population. Among the significant SNPLDB loci, six of them were simultaneously identified in two or more single planting environments and were thought of as the stable SNPLDB loci. Additionally, a total of 115 genes were annotated in the nearby regions of the six stable SNPLDB loci, and 16 common potential candidate genes controlling target traits of them were predicted by two RNA-seq data. One of 16 genes (GH_D06G2161) was mainly expressed in the early ovule-development stages, and the stable SNPLDB locus (LDB_19_62926589) was mapped in its promoter region. CONCLUSION: This study identified the QTL alleles and candidate genes that could provide important insights into the genetic basis of yield-related traits in upland cotton and might facilitate breeding cotton varieties with high yield.

Effect of simulation education and case management on glycemic control in type 2 diabetes.

BACKGROUND: The aim of the study was to investigate whether simulation education (SE) and case management had any effect on glycemic control in type 2 diabetes (T2DM) patients. METHODS: In this single center pilot trial, 100 T2DM patients who received medication and basic diabetes self-management education (DSME) were randomly divided into a control group (n = 50) and an experimental group (n = 50), who received SE and a case management program. Evaluation of biochemical indices was conducted at baseline and after 6 months. DSME consisted of 2-hour group trainings weekly for 2 consecutive weeks followed by 2 × 30 minute education sessions after 3 and 6 months. The SE program comprised additional 50-minute video sessions 3 times in the first week and twice in the second week. The experimental group was supervised by a nurse case manager, who followed up participants at least once a month, and who conducted group sessions once every 3 months, focusing on realistic aspects of physical activity and nutrition, with open discussions about setting goals and strategies to overcome barriers. RESULTS: After 6 months, HbA1c, fasting plasma glucose, and postprandial blood glucose level improvements were superior in the experimental group compared with the control group (P < 0.05). Self-care behavior adherence scores of healthy diet (P = 0.001), physical activity (P = 0.043), self-monitoring of blood glucose (P < 0.001), and reducing risks (P < 0.001) were significantly increased in the experimental group compared with the control group. CONCLUSIONS: Simulation education and case management added to routine DSME effectively improved glycemic control in T2DM patients.

Comparative Analysis of Transcriptomes to Identify Genes Associated with Fruit Size in the Early Stage of Fruit Development in Pyrus pyrifolia.

Pear (Pyrus L.) is an important commercial fruit in the world. The fruit size is one of the important characters in fruit quality. The previous research reported that the fruit size of pear was mainly caused by the number of cell in about 40 days after blossom (DAB) in nature. However, studies about the mechanisms underlying cell division in young fruit development are very limited in pear. Two pear accessions codenamed 'GH59B' with big fruit and 'GH81S' with small fruit in three stages were sampled and the RNA-seq high-throughput sequencing was used to evaluate changes of gene transcription levels in the early stage of fruit development. The difference of cell size among two samples was little in 40 DAB, implying that the difference of the fruit size was caused by the number of the cell. More than 274,517,982 high quality reads from six libraries of fruit development were sequenced. A total of 797 differentially expressed genes (DEGs) were identified. Three cytokinin dehydrogenase genes and two gibberellin 2-beta-dioxygenase gene were identified in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways related to zeatin and gibberellin. Their expression was upregulated at 20 DAB in 'GH81S' and at 30 DAB in 'GH59B', suggesting that the small fruit size might be related to the early degradation of cytokinin and gibberellin inducing a short period of cell division. A total of 38 DEGs of transcription factors were found and 23 DEGs including NAC, ERF and bHLH transcription factors were highly related with cytokinin dehydrogenase and gibberellin dioxygenase genes. Altogether, the results of the present study provide information from a comprehensive gene expression analysis and insight into the molecular mechanism underlying the difference of fruit size in Pyrus pyrifolia.

Analysis of synonymous codon usage patterns in the edible fungus Volvariella volvacea.

In this study, trends in synonymous codons usage of Volvariella volvecea have been first examined by analysis of complete coding sequences and gene chip data. The results showed that GC content at three codon positions are obviously different and there were several factors shaping the codon usage of V. volvacea genes, including base composition. The comparison of codon usage among four edible fungi such as V. volvacea, Agaricus bisporus, Coprinopsis cinerea, and Pleurotus ostreatus indicated that the similar codon usage pattern was used among V. volvacea, A. bisporus and P. ostreatus, but there was significantly different codon usage pattern of C. cinerea. Two arrays of optimal codons were determined by effective number of codons (ENC) values and gene chip database separately, resulting that most of the ENC-predicted optimal codons were included in the array of gene chip resulted optimal codons. This study can provide useful information for codon usage pattern analysis and gene transformation of V. volvacea.

Methylated Biochemical Fulvic Acid-Derived Hydrogels with Improved Swelling Behavior and Water Retention Capacity.

Although humic acids (HAs) have been used to prepare absorbent hydrogels, their applications in many areas, such as agriculture, wastewater treatment and hygienic products, are not satisfactory due to their low solubility in organic solvents. In this work, biochemical fulvic acid (BFA), as a kind of HA, was initially methylated for preparation of the methylated BFA (M-BFA), which contributed to enhancing the solubility in organic solvents. Then, M-BFA reacted with N,N'-methylene diacrylamide (MBA) in the N,N-Dimethylacrylamide (DMAA) solution, and the expected hydrogel (M-BFA/DMAA) was successfully obtained. XPS confirmed that there were more C=O and C-N groups in M-BFA/DMAA than in DMAA; thus, M-BFA/DMAA was able to offer more reactive sites for the water adsorption process than DMAA. The combined results of BET and SEM further demonstrated that M-BFA/DMAA possessed a larger BET surface area, a larger pore volume and a more porous structure, which were favorable for the transfer of water and accessibility of water to active sites, facilitating water adsorption and storage. In addition, the swelling ratio and water retention were investigated in deionized (DI) water at different conditions, including test times, temperatures and pHs. Amazingly, the swelling ratio of M-BFA/DMAA was 10% higher than that of DMAA with the water retention time from 100 to 1500 min. Although M-BFA/DMAA and DMAA had similar temperature sensitivities, the pH sensitivity of M-BFA/DMAA was 0.9 higher than that of DMAA. The results proved that M-BFA/DMAA delivered superior water retention when compared to the pristine DMAA. Therefore, the resultant materials are expected to be efficient absorbent materials that can be widely used in water-deficient regions.

CoAl-LDH decorated with cerium oxide as an efficient adsorbent for restoring low-concentration phosphate in wastewater.

The requirement for the removal of phosphorus (P) from wastewater has become progressively stringent, therefore, it is essential to remove low-concentration phosphate from secondary effluents through a tertiary treatment. One of the biggest challenges in removing phosphate from wastewater is the development of low-cost, green, and pollution-free adsorbents. In this study, novel, eco-friendly and low-cost CeO2 nanosphere modifying CoAl-LDH nanosheets (CoAl-LDH/CeO2) were successfully fabricated using a classical hydrothermal strategy. The microstructure and morphology of CoAl LDH/CeO2 were characterized using SEM, TEM, FTIR, XRD, TG, XPS, and BET techniques. The performance of the P adsorption from water for CoAl-LDH/CeO2 was investigated. The influences of adsorption parameters, such as adsorbent dosage, pH, phosphate concentration, adsorption time, and experimental temperature, were investigated through batch adsorption experiments. The batch adsorption experiments showed that the P removal by CoAl-LDH/CeO2 could reach 93.4% at room temperature within 60 minutes. CoAl-LDH/CeO2 showed ultrafast and high-efficiency adsorption for low concentration P contaminated wastewater. Pseudo-second order model exhibited better fitting with the kinetics of the phosphate adsorption, while the Freundlich model well-described the isotherm results (R2 > 0.999). Although Cl-, NO3-and SO42- coexisted in the solution, CoAl-LDH/CeO2 still possessed favourable selectivity for phosphates. More importantly, the adsorption capacities of CoAl-LDH/CeO2 retained over 85% after five cycles. Therefore, the low cost and sustainable utilization of CoAl-LDH/CeO2 for the phosphate removal from secondary effluent with phosphate at a low concentration highlights its potential application to alleviate eutrophication.

QTL mapping and transcriptome analysis of sugar content during fruit ripening of Pyrus pyrifolia.

Sugar content is an important trait of fruits. The genetic background of fruits can affect their sugar content in different cultivars. The quantitative trait loci and genes related to sugar content during fruit ripening remain unclear. In this study, we performed quantitative trait locus (QTL) mapping of sugar content. Two QTLs (qSugar-LG6-Chr7 and qSugar-LG12-Chr3) were identified based on their total sugar contents. A total of 577 and 519 genes were annotated around these two QTL loci. The contents of fructose, sorbitol, glucose, and sucrose were measured at six time points in four cultivars before fruit maturation, including two sweet cultivars ("Zaoshengxinshui" and "ZQ65") and two general cultivars ("Qiushui" and "ZQ82"). In sweet cultivars, sucrose and fructose accumulate substantially, and sorbitol content decreases significantly during fruit ripening. A transcriptome analysis identified 125 upregulated and 222 downregulated differentially expressed genes (DEGs) in sweet cultivars. Two sucrose transport genes (PpSUT, LOC103964096, and LOC103940043) were negatively correlated with sugar content. A weighted gene co-expression network analysis showed that two genes, sorbitol dehydrogenase (PpSDH, LOC103960512 and LOC103960513), around the locus of qSugar-LG6-Chr7 were negatively co-expressed with the total sugar content, which was downregulated in the sweet cultivars. PpSDH and PpSUT may play important roles in regulating sugar content during pear ripening. Transcriptome analysis also revealed that some DEGs were related to sugars (PpS6PDH and ATP-PpPFK), hormones (PpARG7), and transcription factors (PpEMB1444, PpCYP734A1, and PpWRKY50). In conclusion, this study provides new insights into the molecular mechanisms associated with sugar content in the fruit ripening of Pyrus pyrifolia.

Revealing the role of the rhizosphere microbiota in reproductive growth for fruit productivity when inorganic fertilizer is partially replaced by organic fertilizer in pear orchard fields.

In order to address the global crisis in pear productivity, there has been increased attention given to advocating for the use of organic fertilizers. As part of this effort, researchers have been investigating the microbial properties of organic fertilizers to better understand their potential impact on fruit productivity. Our research focused specifically on the impact of four different ratios of sheep manure (SM) and chemical fertilizers (CF) on pear productivity. We found that replacing CF with SM resulted in a proliferation of gammaproteobacteria, Chlamydiae, Bastocatellia and Clostridia in the soil rhizosphere, which is the region around the roots of plants where most nutrient uptake occurs. Using redundancy analysis, we were able to determine that SM was particularly effective at promoting the growth of gammaproteobacteria and clostridia, which were associated with C:N ratios around 14:1 as well as the availability of K, Fe, Zn and Cu. This combination of factors was conducive to a transition from vegetative growth to reproductive growth, resulting in an increase in pear production from 43 to 56 tons per hectare. We also discovered that Blastociella acts as a buffering system in regulating soil acidity. Taken together, our findings indicate that a combination of SM and CF can improve the abundance of beneficial bacteria in the rhizosphere, leading to an increase in pear productivity.

Initial analytical theory of plasma disruption and experimental evidence.

It is a great physical challenge to achieve controlled nuclear fusion in magnetic confinement tokamak and solve energy shortage problem for decades. In tokamak plasma, large-scale plasma instability called disruption will halt power production of reactor and damage key components. Prediction and prevention of plasma disruption is extremely urgent and important. However, there is no analytical theory can elucidate plasma disruption physical mechanism yet. Here we show an analytical theory of tokamak plasma disruption based on nonextensive geodesic acoustic mode theory, which can give the physical mechanism of disruption. The proposed theory has not only been confirmed by experimental data of disruption on T-10 device, but also can explain many related phenomena around plasma disruption, filling the gap in physical mechanism of tokamak plasma disruption.

Effectiveness, safety, and acceptability of postplacental insertion of GyneFix postpartum intrauterine device among women undergoing cesarean section: A multicenter prospective cohort study in China.

OBJECTIVES: To assess the effectiveness, safety, and acceptability of postplacental insertion of GyneFix postpartum intrauterine device (PPIUD) in women undergoing cesarean section (C-section). STUDY DESIGN: We conducted a prospective cohort study at 14 hospitals in four eastern coastal provinces of China between September 2017 and November 2020. A total of 470 women who underwent C-section and consented to the postplacental insertion of GyneFix PPIUD were enrolled, and 400 completed the 12-month follow-up. Participants were interviewed in the wards after delivery and followed up at 42 days, and months 3, 6, and 12 after delivery. We used Pearl Index (PI) to measure the rate of contraceptive failure, life-table method to measure the rate of PPIUD discontinuation, including IUD expulsion, and Cox regression model to explore the risk factors associated with discontinuation of the device. RESULTS: Nine pregnancies were detected during the first year after GyneFix PPIUD insertion: seven were due to device expulsion and two occurred with PPIUD in situ. The PIs for overall 1-year pregnancy rate and pregnancies with IUD in situ were 2.3 (95% CI: 1.1-4.4) and 0.5 (95% CI: 0.1-1.9), respectively. The 6- and 12-month cumulative expulsion rates for PPIUD expulsion were 6.3% and 7.6%, respectively. The overall 1-year continuation rate was 86.6% (95% CI: 83.3-89.8). We did not identify any patient with insertion failure, uterine perforation, pelvic infection, or excess bleeding due to GyneFix PPIUD insertion. Women's age, education, occupation, previous history of C-section, parity, and breastfeeding were not associated with removal of GyneFix PPIUD in the first year of use. CONCLUSIONS: Postplacental insertion of GyneFix PPIUD is effective, safe, and acceptable for women undergoing C-section. Expulsion is the most common reason for GyneFix PPIUD discontinuation and pregnancy. The expulsion rate for GyneFix PPIUD is lower than that for framed IUDs, but more evidence is needed for a firm verdict.

Multilayer Graphene Oxide Supported ZIF-8 for Efficient Removal of Copper Ions.

To address the performance deterioration of ZIF-8 for the adsorption of copper ions caused by powder volume pressure and particle aggregation, we employed multilayer graphene oxide (MGO) as a support to prepare composite adsorbents (MGO@ZIF-8) by using the in situ growth of ZIF-8 on MGO. Due to a good interfacial compatibility and affinity between ZIF-8 and graphene nanosheets, the MGO@ZIF-8 was successfully prepared. The optimal Cu2+ adsorption conditions of MGO@ZIF-8 were obtained through single factor experiments and orthogonal experiments. Surprisingly, the Cu2+ adsorption capacity was significantly improved by the integration of MGO and ZIF-8, and the maximum Cu2+ adsorption capacity of MGO@ZIF-8 reached 431.63 mg/g under the optimal adsorption conditions. Furthermore, the kinetic fitting and isotherm curve fitting confirmed that the adsorption law of Cu2+ by MGO@ZIF-8 was the pseudo-second-order kinetic model and the Langmuir isotherm model, which indicated that the process of Cu2+ adsorption was monolayer chemisorption. This work provides a new approach for designing and constructing ZIF-8 composites, and also offers an efficient means for the removal of heavy metals.

Pancreatic injury following immune checkpoint inhibitors: A systematic review and meta-analysis.

Background: Pancreatic injury (pancreatitis, amylase/lipase elevation) is a rare adverse event of immune checkpoint inhibitors (ICIs). With the high number of clinical studies on ICIs, the incidence and characteristics of associated pancreatic injury (PI) need to be reevaluated. Methods: A systematic review and meta-analysis was conducted to assess the incidence of PI in cancer patients who received ICIs in randomized controlled trials (RCTs). PubMed, Embase, the ASCO, ESMO, and AACR conference proceedings before 1 April 2022, were investigated for relevant research. Results: 50 RCTs involving 35,223 patients were included. The incidence of ICIs-PI was 2.22% (95% CI = 1.94%-2.53%). The incidence of PI was 3.76% (95% CI = 1.84-7.67%) when combining two ICIs, which was higher than single ICIs [2.25% (95% CI = 1.91-2.65%)]. The ICIs were ranked from high to low based on PI incidence: PD-L1 inhibitors 3.01% (95% CI = 1.86-4.87%), CTLA-4 inhibitors 2.92% (95% CI = 0.99-8.65%) and PD-1 Inhibitor 2% (95% CI = 1.67-2.39%). The ICI with the highest rate of PI was pembrolizumab 7.23.% (95% CI = 1.69-30.89%). In addition, the incidence of severe ICIs-PI was 2.08% (95% CI = 1.76-2.46%); and the incidence of severe PI was 2.32% (95% CI = 1.76-3.06%) when combining two ICIs, which was higher than single ICI [1.95% (95% CI = 1.58-2.41%)]. The ICIs were ranked from high to low according to the incidence of severe PI: PD-L1 inhibitors 3.1% (95% CI = 1.7-5.64%), CTLA-4 inhibitors 2.69% (95% CI = 0.76-9.49%), PD-1 inhibitors 1.80% (95% CI = 1.41-2.29%). Conclusion: Treatment with multiple ICIs result in a higher incidence of PI compared to single ICIs, irrespective of the grade of pancreatic injury. The incidence of PI caused by PD-L1 inhibitors is higher than that of CTLA-4 inhibitors and PD-1 Inhibitor, and Pembrolizumab has the highest rate of ICIs-PI. Although the incidence of ICIs-PI is not high, they are usually severe (≥ grade 3 events).

Genome-Wide Identification and Analysis of High-Copy-Number LTR Retrotransposons in Asian Pears.

A large proportion of the genome of 'Suli' pear (Pyrus pyrifolia) contains long terminal repeat retrotransposons (LTR-RTs), which suggests that LTR-RTs have played important roles in the evolution of Pyrus. Further analysis of retrotransposons, particularly of high-copy-number LTR-RTs in different species, will provide new insights into the evolutionary history of Pyrus. A total of 4912 putative LTR-RTs classified into 198 subfamilies were identified in the 'Suli' pear genome. Six Asian pear accessions, including cultivars and wild species, were resequenced. The comparison of copy number for each LTR-RT subfamily was evaluated in Pyrus accessions, and data showed up to four-fold differences for some subfamilies. This contrast suggests different fates for retrotransposon families in the evolution of Pyrus. Fourteen high-copy-number subfamilies were identified in Asian pears, and more than 50% of the LTR-RTs in the genomes of all Pyrus accessions were from these 14 identified LTR-RT subfamilies. Their average insertion time was 3.42 million years ago, which suggests that these subfamilies were recently inserted into the genome. Many homologous and specific retrotransposon insertion sites were identified in oriental and occidental pears, suggesting that the duplication of retrotransposons has occurred throughout almost the entire origin and evolution of Pyrus species. The LTR-RTs show high heterogeneity, and their copy numbers vary in different Pyrus species. Thus, our findings suggest that LTR-RTs are an important source of genetic variation among Pyrus species.

Study of the luminescence properties of a novel rare earth complex Tb(DPC)(2)2H2O.

Rare earth complex Tb(DPC)(2)2H(2)O was synthesized by introducing Pyridine-2,6-dicarboxylic acid(H(2)DPC) as the ligand and characterized by UV, fluorescent and infrared spectra as well as elemental analysis. The complex exhibited ligand-sensitized green emission, and it has the higher sensitized luminescent efficiency and longer lifetime. The effect and mechanism of the ligand (H(2)DPC) on the luminescence properties of terbium complex was discussed. In device ITO/PVK/Tb(DPC)(2)2H(2)O/Al, Tb(3+) may be excited by intramolecular energy transfer from ligand as observed by electroluminescence. The main emitting peak at 545 nm can be attributed to the transition of (5)D(4)-->(7)F(5) of Tb(3+) ion and this process results in the enhancement of green emission from electroluminescence device.