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Objective: To evaluate the effects of auricular acupoint bloodletting (AB) and auricular acupressure (AA) on sleep quality and the levels of melatonin (MT), glutamic acid (Glu), and γ -aminobutyric acid (GABA) in college students with primary insomnia, and to explore the possible mechanism., Methods: Totally 74 college students at Hebei University of Chinese Medicine with primary insomnia were selected from October 2019 to October 2020. All patients were assigned to AB+AA group (37 cases, received combination of AB and AA) and AA group (37 cases, received only AA on the same acupoints) by a random number table. Each group was treated twice a week for 4 weeks. The Pittsburgh Sleep Quality Index (PSQI) score, Chinese medicine (CM) syndrome score, total effective rate, serum concentrations of MT, Glu, and GABA, and Glu/GABA ratio were compared between the two groups after treatment and at follow-up. The safety of therapy was also evaluated., Results: After 4-week treatment, the total scores of PSQI, each PSQI component score, and the CM syndrome scores in both groups all decreased (P<0.05); the serum MT concentrations in both groups all increased (P<0.05). The concentrations of Glu and GABA in the AB+AA group were significantly higher than those in the AA group after treatment (P<0.05). However, there was no significant difference in the ratio of Glu/GABA in both groups before and after treatment (P>0.05). At follow-up, the CM syndrome score in the AB+AA group was significantly lower than that in the AA group (P<0.05). There was no significant difference between the two groups in total effective rates and adverse events (P>0.05)., Conclusions: Both AB+AA and AA can relieve insomnia symptoms, but a stronger long-term effect were observed for AB+AA. AB+AA can promote the secretion of MT, increase the levels of Glu and GABA more effective than AA, and regulate their imbalance, and thus it may be benificial for treating insomnia., (© 2022. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Carboxylesterases 1A (CES1A) is a key enzyme responsible for the hydrolytic metabolism of a great deal of endogenous and exogenous substrates bearing ester- or amide-bond(s). This study aimed to decipher the species difference in CES1A-mediated hydrolytic metabolism by using a newly developed bioluminescence CES1A sensor (termed NLMe) as the probe substrate, while the liver microsomes from six different mammalian species (human, cynomolgus monkey, dog, minipig, rat and mouse) were used as the enzyme sources. Metabolite profiling demonstrated that all tested liver microsomes from various species could catalyze NLMe hydrolysis, but significant difference in hydrolytic rate was observed. Kinetic plots of NLMe hydrolysis in liver microsomes from different species showed that the inherent clearance rates (C lint ) of NLMe in human liver microsomes (HLM), cynomolgus monkey liver microsomes (CyLM), and pig liver microsome (PLM) were comparable, while the C lint values of NLMe in dog liver microsomes (DLM), mouse liver microsomes (MLM), and rat liver microsomes (RLM) were relatively small. Moreover, chemical inhibition assays showed that NLMe hydrolysis in all tested liver microsomes could be competently inhibited by BNPP (a potent broad-spectrum inhibitor of CES), but CUA (a selective inhibitor of human CES1A) only inhibited NLMe hydrolysis in human liver microsomes and dog liver microsomes. In summary, the species differences in CES1A-catalyzed NLMe hydrolysis were carefully investigated from the views of the similarities in metabolite profile, hydrolytic kinetics and inhibitor response. All these findings provide new insights into the species differences in CES1A-mediated hydrolytic metabolism and suggest that it is necessary for the pharmacologists to choose appropriate animal models to replace humans for evaluating the in vivo effects of CES1A inhibitors., 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.)

Most reports on signal peptides focus on their ability to affect the normal folding of proteins, thereby affecting their secreted expression, while few studies on its effects on enzymatic properties were published. Therefore, biochemical characterization and comparison of alginate lyase rALYI1/rALYI1-1 (rALYI1: without signal peptides; rALYI1-1:with signal peptides) were conducted in our study, and the results showed that the signal peptide affected the biochemical properties, especially in temperature and pH. rALYI1 (32.15 kDa) belonging to polysaccharide lyase family 7 was cloned from sea-cucumber-gut bacterium Tamlana sp. I1. The optimum temperature of both rALYI1 and rALYI1-1 was 40 °C, but the former had a wider optimum temperature range and better thermal stability. The optimum pH of rALYI1 and rALYI1-1 were 7.6 and 8.6, respectively. The former was more stable and acid resistant. Noticeably, rALYI1 was a salt-activated enzyme and displayed remarkable salt tolerance. Alginate, an essential polysaccharide in algae and Pseudomonas aeruginosa biofilms, is composed of α-L-guluronate and β-D-mannuronate. It is also found in our study that rALYI1 is also effective in removing mature biofilms compared with controls. In conclusion, the signal peptide affects several biochemical properties of the enzyme, and alginate lyase rALYI1 may be an effective method for inhibiting biofilm formation of Pseudomonas aeruginosa.

Identification of the evolution history and genetic diversity of a species is important in the utilization of novel genetic variation in this species, as well as for its conservation. Pistacia chinensis is an important biodiesel tree crop in China, due to the high oil content of its fruit. The aim of this study was to uncover the genetic structure of P. chinensis and to investigate the influence of intraspecific gene flow on the process of domestication and the diversification of varieties. We investigated the genetic structure of P. chinensis , as well as evolution and introgression in the subpopulations, through analysis of the plastid and nuclear genomes of 39 P . chinensis individuals from across China. High levels of variation were detected in the P. chinensis plastome, and 460 intraspecific polymorphic sites, 104 indels and three small inversions were identified. Phylogenetic analysis and population structure using the plastome dataset supported five clades of P. chinensis . Population structure analysis based on the nuclear SNPs showed two groups, clearly clustered together, and more than a third of the total individuals were classified as hybrids. Discordance between the plastid and nuclear genomes suggested that hybridization events may have occurred between highly divergent samples in the P. chinensis subclades. Most of the species in the P. chinensis subclade diverged between the late Miocene and the mid-Pliocene. The processes of domestication and cultivation have decreased the genetic diversity of P. chinensis. The extensive variability and structuring of the P. chinensis plastid together with the nuclear genomic variation detected in this study suggests that much unexploited genetic diversity is available for improvement in this recently domesticated species., 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 Han, Zhang, Xian, Xu, Cui, Liu, Wang, Li, Li and Xie.)

A surge in the prevalence of obesity and metabolic syndrome, which promote systemic inflammation, underlies an increase in cardiometabolic disease. Free fatty acid receptor 4 is a nutrient sensor for long-chain fatty acids, like ω3-polyunsaturated fatty acids (ω3-PUFAs), that attenuates metabolic disease and resolves inflammation. Clinical trials indicate ω3-PUFAs are cardioprotective, and this review discusses the mechanistic links between ω3-PUFAs, free fatty acid receptor 4, and attenuation of cardiometabolic disease.

Statement of Problem: Screening for temporomandibular disorders (TMDs) is important in research and clinical practice. The short-form Fonseca Anamnestic Index (SFAI) was recently introduced but had only been validated for muscle disorders., Purpose: The purpose of this clinical study was to determine the diagnostic accuracy of the SFAI and its discrete and pooled items in relation to the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) benchmark., Material and Methods: A total of 866 consecutive participants with TMDs and 57 TMD-free controls (aged ≥18 years) were recruited. The participants (n=923; mean age 32.8 ±13.3 years; women 79.2%) answered the FAI, and TMD diagnoses were derived based on the DC/TMD protocol and algorithms. The 5-item SFAI, which comprised 2 pain-related and 3 function-related TMD questions, was subsequently acquired and assessed with reference to the DC/TMD diagnoses. The receiver operating characteristics (ROC) was used to verify accuracy (area under the curve [AUC]) and the best cutoff points. Sensitivity, specificity, predictive values, and likelihood ratios were also examined., Results: Pain-related (PT) and intra-articular (IT) TMDs were present in 48.3% (446/923) and 82.7% (763/923) of the participants, respectively. The SFAI demonstrated high accuracy for identifying all TMDs, PT, and IT (AUC of 0.97, 0.99, and 0.97, respectively). The best cutoff points were 12.5 for all TMDs/IT and 17.5 for PT. Sensitivity of the SFAI ranged from 90.7% to 97.5% while specificity varied from 93.0% to 96.5%, with the highest values for PT. As positive predictive values (99.4% to 99.5%) were greater than negative ones (41.7% to 83.3%), the SFAI was better at detecting the presence than the absence of TMDs. With reference to PT, the sensitivity, and specificity of the 2 discrete and pooled pain-related questions (questions 3 and 4), extended from 82.3% to 99.3% and 77.2% to 96.5% respectively. With regard to IT diagnoses, sensitivity and specificity ranged from 56.0% to 98.3% and 86.0% to 98.3% for the 3 discrete and pooled function-related items (questions 1, 2, and 5)., Conclusions: The SFAI presented high degrees of diagnostic accuracy in relation to the DC/TMD and can be used for screening TMDs. SFAI scores between 15 and 50 points should be used to identify the presence of TMDs, with scores ≥20 points specifying possible pain-related TMDs., (Copyright © 2021 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

Objectives: Proximal interruption of the pulmonary artery (PIPA) has various clinical manifestations. This review focused on and summarized the clinical and radiological features of PIPA, based on relevant literature studies., Methods: The study included a total of 25 PIPA cases in the Guangzhou Women and Children's Medical Center between January 2015 and December 2021. Conventional chest photographs and chest computed tomography angiography (CCTA) of patients with PIPA were analyzed and summarized., Results: The radiological results showed that 17 cases were right-sided and 8 cases were left-sided PIPA. Additionally, the percentage of pulmonary hypoplasia on the affected side was 44%, 36% for pulmonary hypertension, 28% for the mosaic sign, 20% for subpleural cystic lucency shadow, 20% for subpleural serrated shadow, 20% for collateral vessel thickening, 16% for subpleural band-like parenchyma, 12% for pneumonia, and 56% for patent ductus arteriosus., Conclusion: The clinical manifestations of PIPA are non-specific. Awareness of this anomaly, based on radiological manifestations, particularly those observed on CCTA images, is important for ruling out alternative diagnoses and implementing appropriate management., 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., (© 2022 Zhang, Cao, Zhou, Wang, Wu and Zhang.)

Ice cores from alpine glaciers are unique archives of past global and regional climate conditions. However, recovering climate records from these ice cores is often hindered by the lack of a reliable chronology, especially in the age range of 100 to 500 anni (a) for which radiometric dating has not been available so far. We report on radiometric 39 Ar dating of an ice core from the Tibetan Plateau and the construction of a chronology covering the past 1,300 a using the obtained 39 Ar ages. This is made possible by advances in the analysis of 39 Ar using the laser-based detection method atom trap trace analysis, resulting in a twofold increase in the upper age limit of 39 Ar dating. By measuring the anthropogenic 85 Kr along with 39 Ar we quantify and correct modern air contamination, thus removing a major systematic uncertainty of 39 Ar dating. Moreover, the 85 Kr data for the top part of the ice core provide information on firn processes, including the age difference between the ice and its enclosed gas. This first application of 39 Ar and 85 Kr to an ice core facilitates further ice cores from nonpolar glaciers to be used for recovering climate records of the Common Era, a period including pronounced anomalies such as the Little Ice Age and the Medieval Warm Period.

Epigenetic alterations, including DNA methylation, play crucial roles in the tumor. Epigenetic drugs like DNA methyltransferase-1 (DNMT1) inhibitors have been exhibited positive effects in cancer treatment. However, the role of DNMT1 in oral squamous cell carcinoma (OSCC) is less clearly described. What is more, the effects on the immune microenvironment of DNMT1 have not become appreciated. In this research, we determine the expression levels of DNMT1 and the association of prognosis by analyzing human OSCC tissue microarrays. Two different types of immunocompetent mouse OSCC models were established to explore the effects of DNMT1 inhibitor on the tumor microenvironment(TME). We identified DNMT1 was highly expressed both in human and mouse OSCC tissues. The expression levels of DNMT1 was also correlated with the immunosuppressive molecules and tumor-promoter such as VISTA, PD-L1, B7-H4, and PAK2, indicating a worse prognosis. Of particular concern is that DNMT1 inhibition improved TME and delayed tumor growth by decreasing myeloid-derived suppressor cells (MDSCs) and increasing tumor-infiltrating T cells. Our data suggests that DNMT1 play a key role in OSCC and has a possible immunotherapeutic marker treatment., 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.)

Immunotherapy is one of the most promising clinical modalities for the treatment of malignant tumors and has shown excellent therapeutic outcomes in clinical settings. However, it continues to face several challenges, including long treatment cycles, high costs, immune-related adverse events, and low response rates. Thus, it is critical to predict the response rate to immunotherapy by using imaging technology in the preoperative and intraoperative. Here, the latest advances in nanosystem-based biomaterials used for predicting responses to immunotherapy via the imaging of immune cells and signaling molecules in the immune microenvironment are comprehensively summarized. Several imaging methods, such as fluorescence imaging, magnetic resonance imaging, positron emission tomography imaging, ultrasound imaging, and photoacoustic imaging, used in immune predictive imaging, are discussed to show the potential of nanosystems for distinguishing immunotherapy responders from nonresponders. Nanosystem-based biomaterials aided by various imaging technologies are expected to enable the effective prediction and diagnosis in cases of tumors, inflammation, and other public diseases., (© 2022 Wiley-VCH GmbH.)

Tritium deposited in soil forms HTO and OBT. To further understand the changes of HTO and OBT in different years, HTO and OBT in the soil around Qinshan Nuclear Power Base in different sampling years were measured. According to the annual distribution of HTO and OBT in the surface soil, it could be inferred whether there was a long-term release of tritium in the observed year. From the depth distribution of different years, OBT tends to migrate to the deep. From 2015 to 2020, the correlation analysis between OBT and HTO/soil organic matter showed that HTO contributed more to OBT in surface soil at 250-2000 μm and 53-250 μm particle sizes, but this conclusion did not apply to deep soil. However, there was no significant relationship between OBT activity and soil organic matter content., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Single-cell RNA sequencing (scRNA-seq) provides unique insights into the pathology and cellular origin of disease. We introduce single-cell disease relevance score (scDRS), an approach that links scRNA-seq with polygenic disease risk at single-cell resolution, independent of annotated cell types. scDRS identifies cells exhibiting excess expression across disease-associated genes implicated by genome-wide association studies (GWASs). We applied scDRS to 74 diseases/traits and 1.3 million single-cell gene-expression profiles across 31 tissues/organs. Cell-type-level results broadly recapitulated known cell-type-disease associations. Individual-cell-level results identified subpopulations of disease-associated cells not captured by existing cell-type labels, including T cell subpopulations associated with inflammatory bowel disease, partially characterized by their effector-like states; neuron subpopulations associated with schizophrenia, partially characterized by their spatial locations; and hepatocyte subpopulations associated with triglyceride levels, partially characterized by their higher ploidy levels. Genes whose expression was correlated with the scDRS score across cells (reflecting coexpression with GWAS disease-associated genes) were strongly enriched for gold-standard drug target and Mendelian disease genes., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

A new climbing species, Ficusmotuoensis Zhen Zhang & Hong Qing Li in Moraceae from southwest China has been described and illustrated in this paper. The new species resembles F.disticha , F.diversiformis and F.hederacea , but differs from these in the medium-sized acrophylls, shorter peduncle, as well as larger and spotted syconium. According to the morphological traits and phylogenetic placement, the new species belongs to Ficussubg.Synoeciasect.Apiosycea. Besides, the new species deviates from the common distribution pattern compared to the other members of sect. Apiosycea, indicating that it could be very useful for exploring the biogeography of sect. Apiosycea., (Zhen Zhang, Mei-Jiao Zhang, Jian-Hang Zhang, De-Shun Zhang, Hong-Qing Li.)

A visible-light-promoted iodine-mediated homo-coupling of diazo was first described. A series of tetrasubstituted olefins were synthesized in high yields and with low to high Z -selectivities from phenyldiazoacetates. For 3-diazooxindoles, isoindigo derivatives were provided in moderate to high yields and with excellent E -selectivities. Experimental results showed that the reaction proceeded through a diiodo intermediate. The synthetic usefulness of this reaction was illustrated by the synthesis of maleimide derivatives and dispiro epoxy.

Effective pyroptosis induction is a promising approach to potentiate cancer immunotherapy. However, the actual efficacy of the present pyroptosis inducers can be weakened by successive biological barriers. Here, a cascaded pH-activated supramolecular nanoprodrug (PDNP) with a stepwise size shrinkage property is developed as a pyroptosis inducer to boost antitumor immune response. PDNPs comprise multiple poly(ethylene glycol) (PEG) and doxorubicin (DOX) drug-polymer hybrid repeating blocks conjugated by ultra-pH-sensitive benzoic imine (bzi) and hydrazone (hyd) bonds. The PEG units endow its "stealth" property and ensure sufficient tumor accumulation. A sharp switch in particle size and detachment of PEG shielding can be triggered by the acidic extracellular pH to achieve deep intratumor penetration. Following endocytosis, second-stage size switching can be initiated by more acidic endolysosomes, and PDNPs disassociate into ultrasmall cargo to ensure accurate intracellular delivery. The cascaded pH activation of PDNPs can effectively elicit gasdermin E (GSDME)-mediated pyroptosis to enhance the immunological response. In combination with anti-PD-1 antibody, PDNPs can amplify tumor suppression and extend the survival of mice, which suggests a powerful immune adjuvant and pave the way for high-efficiency immune checkpoint blockade therapy., (© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Long non-coding RNA (lncRNA) X inactivate-specific transcript (XIST) has been found dysregulated in a variety of human tumors and influenced the clinicopathologic characteristics in cancer patients. Therefore, we systematically searched relevant literature that has identified the correlation of lncRNA XIST expression and clinical outcomes of tumor patients and conducted this meta-analysis to elucidate the clinical prognostic value of long noncoding RNA XIST in human tumors. A comprehensive literature search was performed from PubMed, Web of Science, EMBASE, and Cochrane library databases up to August 1, 2019. Pooled hazard ratios (HRs) or odds ratios (ORs) with a 95% confidence interval (95% Cl) were calculated to evaluate the prognosis, as well as the clinicopathological parameters of XIST, respectively. We also further validated this meta-analysis using The Cancer Genome Atlas (TCGA) dataset. The outcome revealed that XIST overexpression in tumor tissue was interacted to a poor overall survival (OS) (HR=0.52, 95% CI: 0.44-0.61, p<0.0001), disease-free survival (DFS) (HR=0.50; 95% CI: 0.36-0.69, p<0.0001), tumor type (digestive system malignancies, HR=0.53; 95% CI: 0.44-0.63, p<0.0001); nondigestive system malignancies, HR=0.48; 95% CI: 0.34-0.67, p<0.0001), lymph node metastasis(LNM) (OR=0.61, 95% CI: 0.37-1.00; p=0.048), differentiation (OR=1.46; 95% CI: 0.94-2.29; p=0.096), distant metastasis (DM) (OR=0.48, 95% CI: 0.31-0.75; p=0.001), tumor size (OR=0.59, 95% CI: 0.38-0.92; p=0.019), and tumor stage (OR=2.36; 95% CI: 1.62-3.43; p<0.001). XIST could have potential value in early diagnosis and result in prediction and provide a novel view for the therapeutic target in clinical application.

Endoreduplication is prevalent during plant growth and development, and is often correlated with large cell and organ size. Despite its prevalence, the transcriptional regulatory mechanisms underlying the transition from mitotic cell division to endoreduplication remain elusive. Here, we characterize ETHYLENE-RESPONSIVE ELEMENT BINDING FACTOR 4 (ERF4) as a positive regulator of endoreduplication through its function as a transcriptional repressor. ERF4 was specifically expressed in mature tissues in which the cells were undergoing expansion, but was rarely expressed in young organs. Plants overexpressing ERF4 exhibited much larger cells and organs, while plants that lacked functional ERF4 displayed smaller organs than the wild-type. ERF4 was further shown to regulate cell size by controlling the endopolyploidy level in the nuclei. Moreover, ERF4 physically associates with the class I TEOSINTE BRANCHED 1/CYCLOIDEA/PCF (TCP) protein TCP15, a transcription factor that inhibits endoreduplication by activating the expression of a key cell-cycle gene, CYCLIN A2;3 (CYCA2;3). A molecular and genetic analysis revealed that ERF4 promotes endoreduplication by directly suppressing the expression of CYCA2;3. Together, this study demonstrates that ERF4 and TCP15 function as a module to antagonistically regulate each other's activity in regulating downstream genes, thereby controlling the switch from the mitotic cell cycle to endoreduplication during leaf development. These findings expand our understanding of how the control of the cell cycle is fine-tuned by an ERF4-TCP15 transcriptional complex., (© 2022 Institute of Botany, Chinese Academy of Sciences.)

Background: As one of the most common tumors, gastric cancer (GC) has a high mortality rate, since current examination approaches cannot achieve early diagnosis. Fusobacterium nucleatum (Fn) primarily colonized in the oral cavity, has been reported to be involved in the development of gastrointestinal tumor. Until now, little is known about the relationship between salivary Fn and GC., Aim: To determine whether salivary Fn could be a biomarker to diagnose GC and explore the influence of Fn on GC cells., Methods: The abundance of Fn in saliva was quantified by droplet digital polymerase chain reaction in 120 GC patients, 31 atrophic gastritis (AG) patients, 35 non-AG (NAG) patients, 26 gastric polyp (GP) patients, and 20 normal controls (NC) from Qilu Hospital of Shandong University from January 2019 to December 2020. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic value of Fn as well as traditional serum tumor markers, including carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9, and CA72-4. Transwell assay and wound-healing assay were conducted to assess the influence of Fn infection on GC cells. The expression of epithelial-mesenchymal transition (EMT) markers was detected using western blot assay., Results: We found that the level of salivary Fn in GC patients was significantly increased compared with those in AG, NAG, and GP patients and NC ( P < 0.001). ROC curve analysis showed a favorable capability of Fn (73.33% sensitivity; 82.14% specificity; area under the curve: 0.813) in GC diagnosis, which was superior to that of CEA, CA19-9, CA72-4, ferritin, and sialic acid. The Fn level in saliva of GC patients was increased as the TNM stage increased. GC patients with lymph node metastasis had higher Fn levels than those without metastasis. Both transwell and wound-healing assays indicated that Fn infection promoted the migration and invasion of GC cells. Western blot analysis showed that Fn infection decreased the expression of E-cadherin and increased the expressions of N-cadherin, vimentin, and snail., Conclusion: Fn abundance in saliva could be used as a promising biomarker to diagnose GC, and Fn infection could promote GC metastasis by accelerating the EMT process., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

A field experiment was conducted to study the effects of different organic material amendments on soil respiration in a flue-cured tobacco field. Five treatments were set up:no fertilizer (NF), chemical fertilizer (NPK), chemical fertilizer+ryegrass (NPKG), chemical fertilizer+wheat straw (NPKS), and chemical fertilizer+tobacco straw biochar (NPKB). The results showed that:① Compared with that under NPK, NPKG and NPKS decreased the temperature sensitivity ( Q 10 ) of total soil respiration and heterotrophic respiration, whereas NPKB increased the Q 10 of heterotrophic respiration. The two-factor fitting model of soil respiration and soil hydrothermal factors accounted for 50%-80% of the variation in soil respiration. ② The addition of organic materials significantly increased the content of soil soluble organic carbon (DOC) and root dry matter. Soil heterotrophic respiration( R h ) was significantly positively correlated with DOC content, and soil autotrophic respiration( R a ) was significantly parabolically correlated with root biomass, with an R 2 of 0.327-0.634. ③ Soil respiration increased first and then decreased during the tobacco growth period. Compared with that under the NF treatment, the NPK treatment significantly promoted soil respiration and its components. Compared with those of the NPK treatment, R s rates were significantly increased by 20.08%, 10.32%, and 9.88% under the NPKG, NPKS, and NPKB treatments, respectively; R h rate increased by 24.21%, 16.51%, and 11.68% respectively, and R a rate was increased by 15.12% in the NPKG treatment. In summary, straw returning and biochar addition significantly increased R h by increasing soil DOC, thereby promoting R s . Incorporation of ryegrass not only increased the R h but also increased R a by promoting the growth and development of roots and therefore the R s .

Gasdermin E (GSDME), as the major executive protein of pyroptosis, has been considered to be linked to antitumor immunity in recent years. However, the role of GSDME in oral squamous cell carcinoma (OSCC) remains to be elucidated. Here, by using a human OSCC tissue microarray, human OSCC tissue, and Tgfbr1 / Pten conditional knockout mice, we found that GSDME was strongly expressed in OSCC and that GSDME expression in primary tumors was higher than that in metastatic lymph nodes. In addition, GSDME expression in OSCC was positively related to better prognosis. Moreover, GSDME-mediated pyroptosis occurred upon stimulation with chemotherapy drugs, and functional knockdown of GSDME attenuated the cisplatin-induced antitumor effect. Consistent with these results, bioinformatic analysis indicated that GSDME expression was positively correlated with the sensitivity of a number of antitumor drugs approved by the US Food and Drug Administration. Inhibition of GSDME expression by small interfering RNA in SCC7 cells significantly increased the expression of the cancer stem cell markers, CD44 and ALDH1. Furthermore, multiplexed immunohistochemistry and flow cytometry indicated that the expression of GSDME positively correlated with tumor-infiltrating CD8 + T cells, granzyme B, and M1 phenotype macrophages. Collectively, these findings demonstrated that GSDME is a potential positive prognostic factor of OSCC, and GSDME-mediated pyroptosis induced by chemotherapy plays a role in antitumor response.

Cyclocarya paliurus is an endemic Chinese tree species with considerable medicinal, timber, and horticultural value. The anthracnose disease of C. paliurus is caused by the fungal pathogen Colletotrichum fructicola , which results in great losses in yield and quality. Here, resistance evaluation of six cultivars of C. paliurus exhibited varying degrees of resistance to C. fructicola infection, where Wufeng was the most resistant and Jinggangshan was the most susceptive. Physiological measurements and histochemical staining assays showed that the Wufeng cultivar exhibits intense reactive oxygen species accumulation and defense capabilities. A multiomics approach using RNA sequencing and metabolome analyses showed that resistance in C. paliurus (Wufeng) is related to early induction of reprogramming of the flavonoid biosynthesis pathway. In vitro antifungal assays revealed that the flavonoid extracts from resistant cultivars strongly inhibited C. fructicola hyphal growth than susceptible cultivars. Relative gene expression analysis further demonstrated the pivotal antifungal role of C. paliurus flavonoids in targeting Colletotrichum appressorium formation. Together, these results represent a novel resistance mechanism of C. paliurus against anthracnose through the reprogramming of flavonoids, which will lay a foundation for breeding anthracnose-resistant varieties and the application of flavonoid extraction of C. paliurus as a natural antifungal treatment., 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 Zheng, Zhang, Qiao, Li, Alkan, Chen and Chen.)

Objective: To observe the clinical efficacy of different treatment frequency of auricular bloodletting combined with auricular point sticking for acne vulgaris., Methods: A total of 90 patients with acne vulgaris were randomized into a treatment group 1 (30 cases, 2 cases dropped off), a treatment group 2 (30 cases, 4 cases dropped off) and a treatment group 3 (30 cases, 5 cases dropped off). Combination therapy of auricular bloodletting and auricular point sticking at Fei (CO 14 ), Shenmen (TF 4 ), Neifenmi (CO 18 ) and Shenshangxian (TG 2 p) were given once a week, twice a week and 3 times a week in the treatment group 1, the treatment group 2 and the treatment group 3 respectively, 4 weeks were as one course and totally 3 courses were required in the 3 groups. Before treatment and after 1, 2, 3 courses of treatment, the scores of global acne grading system (GAGS), skin lesion and quality of life-acne (QoL-Acne) were observed, the clinical efficacy was evaluated after 3 courses of treatment and the recurrence rate was evaluated in follow-up of 1 month after treatment in the 3 groups., Results: Compared before treatment, the scores of GAGS and skin lesion were decreased at each time point in the 3 groups ( P <0.05), the QoL-Acne scores were increased after 1 course of treatment in the treatment group 3 and after 2, 3 courses of treatment in the 3 groups ( P <0.05). There were no statistical differences in scores of GAGS, skin lesion and QoL-Acne among the 3 groups ( P >0.05). There were no statistical differences in effective rate and recurrence rate among the 3 groups ( P >0.05)., Conclusion: Different frequency of auricular bloodletting combined with auricular point sticking have similar efficacy in treating acne vulgaris, all can improve the skin lesion and quality of life in patients with acne vulgaris, and have a cumulative effect and good long-term curative effect.

Dysbiosis of the oral microbiome mediates chronic periodontal disease. Realignment of microbial dysbiosis towards health may prevent disease. Treatment with antibiotics and probiotics can modulate the microbial, immunological, and clinical landscape of periodontal disease with some success. Antibacterial peptides or bacteriocins, such as nisin, and a nisin-producing probiotic, Lactococcus lactis, have not been examined in this context, yet warrant examination because of their biomedical benefits in eradicating biofilms and pathogenic bacteria, modulating immune mechanisms, and their safety profile in humans. This study's goal was to examine the potential for nisin and a nisin-producing probiotic to abrogate periodontal bone loss, the host inflammatory response, and changes in oral microbiome composition in a polymicrobial mouse model of periodontal disease. Nisin and a nisin-producing Lactococcus lactis probiotic significantly decreased the levels of several periodontal pathogens, alveolar bone loss, and the oral and systemic inflammatory host response. Surprisingly, nisin and/or the nisin-producing L. lactis probiotic enhanced the population of fibroblasts and osteoblasts despite the polymicrobial infection. Nisin mediated human periodontal ligament cell proliferation dose-dependently by increasing the proliferation marker, Ki-67. Nisin and probiotic treatment significantly shifted the oral microbiome towards the healthy control state; health was associated with Proteobacteria, whereas 3 retroviruses were associated with disease. Disease-associated microbial species were correlated with IL-6 levels. Nisin or nisin-producing probiotic's ability to shift the oral microbiome towards health, mitigate periodontal destruction and the host immune response, and promote a novel proliferative phenotype in reparative connective tissue cells, addresses key aspects of the pathogenesis of periodontal disease and reveals a new biomedical application for nisin in treatment of periodontitis and reparative medicine., (© 2022. The Author(s).)

Acute Myeloid Leukemia (AML) has a median age at diagnosis of 67 years. The most common curative therapy remains an allogeneic hematopoietic stem cell transplantation (HCT), yet it is complicated by treatment-related mortality (TRM) and ongoing morbidity including graft versus host disease (GVHD) that may impact survival, particularly in older patients. We examined the outcomes and predictors of success in 1321 patients aged 60 years and older receiving a HCT for AML in first complete remission (CR1) from 2007-2017 and reported to the CIBMTR. Outcomes were compared in three age cohorts (60-64; 65-69; 70+). With median follow-up of nearly 3 years, patients aged 60-64 had modestly, though significantly better OS, DFS and lower TRM than those either 65-69 or 70+; cohorts with similar outcomes. Three-year OS for the 3 cohorts was 49.4%, 42.3%, and 44.7% respectively (p = 0.026). TRM was higher with increasing age, cord blood as graft source and HCT-CI score of ≥3. Conditioning intensity was not a significant predictor of OS in the 60-69 cohort with 3-year OS of 46% for RIC and 49% for MAC (p = 0.38); MAC was rarely used over age 70. There was no difference in the relapse rate, incidence of Grade III/IV acute GVHD, or moderate-severe chronic GVHD across the age cohorts. After adjusting for other predictors, age had a small effect on OS and TRM. High-risk features including poor cytogenetics and measurable residual disease (MRD) prior to HCT were each significantly associated with relapse and accounted for most of the adverse impact on OS and DFS. Age did not influence the incidence of either acute or chronic GVHD; while graft type and associated GVHD prophylaxis were most important. These data suggest that age alone is not a barrier to successful HCT for AML in CR1 and should not exclude patients from HCT. Efforts should focus on minimizing residual disease and better donor selection., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

A Gram-stain-positive, orange-pigmented, rod-shaped and flagellated bacterial strain T12 T was isolated from wetland soil in Kunyu Mountain Wetland in Yantai, China. The strain was able to grow at 15-40 °C (optimum 37 °C), at 0.0-9.0% NaCl (optimum 2%, w/v) and at pH 5.5-9.0 (optimum 8.5). A phylogenetic analysis based on the 16S rRNA gene sequence indicated that strain T12 T is a member of the family Planococcaceae, sharing 97.6% and 97.1% sequence similarity with the type strains of Jeotgalibacillus salarius and Jeotgalibacillus marinus, respectively. Genome-based analyses revealed a genome size of 3,506,682 bp and a DNA G + C content of 43.7%. Besides, the genome sequence led to 55.0-74.6% average amino acid identity values and 67.8-74.7% average nucleotide identity values between strain T12 T and the current closest relatives. Digital DNA-DNA hybridization of strain T12 T with the type strains of Jeotgalibacillus proteolyticus and J. marinus demonstrated 19.0% and 20.3% relatedness, respectively. The chemotaxonomic analysis showed that the sole quinone was MK-7. The predominant cellular fatty acids were iso-C 15:0 , anteiso-C 15:0 , C 16:1 ω7c alcohol and iso-C 14:0 . The polar lipids consisted of an unidentified aminolipid, phosphatidylglycerol, diphosphatidylglycerol and two unidentified phospholipids. Based on the polyphasic characterization, strain T12 T is considered to represent a novel species, for which the name Jeotgalibacillus aurantiacus sp. nov. is proposed. The type strain is T12 T (= KCTC 43296  T  = MCCC 1K07171 T )., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Objective: This study explored the viability of using the 5 temporomandibular disorder (TMD) symptoms (5Ts) of the Diagnostic Criteria for TMDs (DC/TMD) as a TMD screener., Study Design: A total of 1039 adults (≥18 years old) with a mean age of 32.65 ± 12.95 years (77.4% women) from a tertiary dental hospital were enrolled. The 5Ts questionnaire (involving items on TMD/facial pain, headaches, temporomandibular joint noises, and closed- and open-locking) was administered, and TMD diagnoses were derived through clinical interviews and examinations, radiographic investigations, and the DC/TMD diagnostic algorithms and diagnostic tree. Diagnostic accuracy of the 5Ts was assessed using the area under the receiver operating characteristics curve and various measures, including sensitivity, specificity, predictive values, and likelihood ratios., Results: Among the participants, 80.2% (n = 833) were 5Ts-positive, and 19.8% (n = 206) were 5Ts-negative, whereas 51.3% and 85.7% received at least 1 pain-related and intra-articular DC/TMD diagnosis, respectively. The 5Ts showed high accuracy for detecting all TMDs, pain-related and intra-articular, with area under the receiver operating characteristics curves of 0.98, 1.00, and 0.98, respectively. Sensitivity ranged from 96.1% to 99.2%, whereas specificity was 100.0%., Conclusions: The 5Ts demonstrated high diagnostic accuracy for identifying pain-related and/or intra-articular disorders., (Copyright © 2021 Elsevier Inc. All rights reserved.)

With the increasing detection rate of early upper gastric cancer and adenocarcinoma of esophagogastric junction, the safety of proximal gastrectomy with clear indications has been verified, and function-preserving proximal gastrectomy has been widely used. However, proximal gastrectomy destructs the normal anatomical structure of esophagogastric junction, resulting in severe postoperative gastroesophageal reflux symptoms and seriously affecting the quality of life. Among various anti-reflux surgery methods, reconstruction of "cardiac valve" has always been the focus of relevant scholars because its similarity with the mechanism of normal anti-reflux. After years of development, evolution and optimization, the designed seromuscular flap anastomosis includes tunnel muscle flap anastomosis, Hatafuku valvuloplasty, single muscle flap anastomosis and double muscle flap anastomosis. The double muscle flap anastomosis has become a research hotspot because it shows good anti-reflux effect in clinical application. This paper reviews the history, research status and hot issues of seromuscular flap anastomosis of esophageal remnant stomach at home and abroad.

Data from 1,364 consecutive subjects with chronic-phase chronic myeloid leukemia (CML) receiving initial imatinib-therapy were interrogated to identify co-variates predicting therapy failure. Subjects were randomly divided into training (n = 908) and validation datasets (n = 456). In the training dataset, WBC count ≥120 × 10E + 9/L, haemoglobin concentration <115 g/L, blood basophils ≥12% and European Treatment and Outcome Study for CML Long-Term Survival (ELTS) risk score were significantly-associated with failure-free survival (FFS). Each co-variate was assigned 1 point to develop the imatinib-therapy failure (IMTF) model except ELTS high-risk category which was assigned 2 points based on multi-variable regression coefficients. Area under receiver-operator characteristic curve values in the IMTF model for 1-, 3- and 5-year FFS were 0.79-0.84 in the training dataset and 0.78-0.85 in the validation dataset. Calibration plots showed high agreement between predicted and observed outcomes. Decision curve analyses indicated subjects benefited from clinical use of this model. Cumulative incidences of imatinib-therapy failure and probabilities of FFS among the 5 risk cohorts (very low-, low-, intermediate-, high- and very high-risk) using the IMTF model were significantly different (all p values < 0.001). The IMTF model also correlated with probabilities of progression-free survival and survival (all p values < 0.001). These data should help physicians optimize TKI-therapy strategy at diagnosis in persons with chronic phase CML., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

The TIR domain-containing adaptor inducing IFN-β (TRIF) is an adaptor molecule that plays a critical role in the Toll-like receptors (TLRs)-mediated innate immune signaling pathway. Lamprey, as the most primitive jawless vertebrate, rely mainly on innate immunity to defend against various pathogens infection. The function of TRIF in lamprey remains unknown. In this study, a homologous adaptor molecule TRIF, named LmTRIF, was identified in Northeast Chinese lamprey (Lethenteron morii). The LmTRIF coding sequence (cds) is 1242 bp in length and encodes 413 amino acids (aa). Domain analysis showed that LmTRIF is characterized with the classical TIR domain and a lack of TRAF6 binding motif. The results of evolutionary tree indicated that the relationship between LmTRIF and other homologous proteins was consistent with the position of lamprey in the species evolutionary history. The relative expression of LmTRIF was highest in the liver of larvae and in the gill of adults, respectively. Cellular immunofluorescence assays showed that LmTRIF was expressed in the cytoplasma in both mammalian cell line HEK 293T and the fish cell line EPC. The double luciferase reporter gene assay showed that the overexpression of LmTRIF promoted the activity of NF-κB, an immune transcription factor downstream of the classical TLR signaling pathway. In this study, we identified the TLR adaptor molecule TRIF from L. morii, a vertebrate more primitive than fish. Our results suggested an important role of LmTRIF in the innate immune signal transduction process of L. morii and is the basis for the origin and evolution of the TLR signaling pathway in the innate immune system in vertebrates., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Mucoepidermoid carcinoma and adenoid cystic carcinoma are the two most common malignancies of salivary gland. Our study aims to explore the role of human endogenous Retrovirus-H long terminal repeat-associating protein 2, transmembrane and immunoglobulin domain-containing 2, and glucocorticoid-induced tumor necrosis factor receptor in adenoid cystic carcinoma and mucoepidermoid carcinoma, and the relationship between human endogenous Retrovirus-H long terminal repeat-associating protein 2, transmembrane and immunoglobulin domain-containing 2, glucocorticoid-induced TNF receptor, oncogenic signaling molecules, and cluster of differentiation 8., Methods: Custom-made human salivary gland tissue microarrays included 81 Adenoid cystic carcinoma, 52 mucoepidermoid carcinoma, 76 normal salivary gland, and 14 pleomorphic adenoma samples. Immunohistochemical analysis of human endogenous Retrovirus-H long terminal repeat-associating protein 2, transmembrane and immunoglobulin domain-containing 2, and glucocorticoid-induced TNF receptor, oncogenic phosphorylated Erk 1/2 , the epithelial-mesenchymal transition (EMT) molecule transforming growth factor β1, and cluster of differentiation 8 was performed with salivary gland tissue microarray of human samples., Results: According to a digital pathological system, we analyzed the correlation of immunostaining. The expression levels of human endogenous Retrovirus-H long terminal repeat-associating protein 2, transmembrane and immunoglobulin domain-containing 2, and glucocorticoid-induced TNF receptor were significantly enhanced in the adenoid cystic carcinoma and mucoepidermoid carcinoma, compared with those of pleomorphic adenoma and NSG samples. However, the expression levels of human endogenous Retrovirus-H long terminal repeat-associating protein 2, transmembrane and immunoglobulin domain-containing 2, and glucocorticoid-induced TNF receptor were independent of the pathological grade of malignancy of mucoepidermoid carcinoma and histological pattern of adenoid cystic carcinoma. They were closely related to phosphorylated Erk1/2 and transforming growth factor β1, but negligibly related to cluster of differentiation 8., Conclusions: These results described that certain immune checkpoint molecules, namely, human endogenous Retrovirus-H long terminal repeat-associating protein 2, transmembrane and immunoglobulin domain-containing 2, and glucocorticoid-induced TNF receptor were overexpressed in Adenoid cystic carcinoma and mucoepidermoid carcinoma, but were independent of pathological grade, and may relate to transforming growth factor β1, phosphorylated Erk1/2, and cluster of differentiation 8., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

A generalized case-cohort design has been used when measuring exposures is expensive and events are not rare in the full cohort. This design collects expensive exposure information from a (stratified) randomly selected subset from the full cohort, called the subcohort, and a fraction of cases outside the subcohort. For the full cohort study with competing risks, He et al. (Scand J Stat 43:103-122, 2016) studied the non-stratified proportional subdistribution hazards model with covariate-dependent censoring to directly evaluate covariate effects on the cumulative incidence function. In this paper, we propose a stratified proportional subdistribution hazards model with covariate-adjusted censoring weights for competing risks data under the generalized case-cohort design. We consider a general class of weight functions to account for the generalized case-cohort design. Then, we derive the optimal weight function which minimizes the asymptotic variance of parameter estimates within the general class of weight functions. The proposed estimator is shown to be consistent and asymptotically normally distributed. The simulation studies show (i) the proposed estimator with covariate-adjusted weight is unbiased when the censoring distribution depends on covariates; and (ii) the proposed estimator with the optimal weight function gains parameter estimation efficiency. We apply the proposed method to stem cell transplantation and diabetes data sets., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: As genetic genetic factors are important in SLE, so screening causative genes is of great significance for the prediction and early prevention in people who may develop SLE. At present, it is very difficult to screen causative genes through pedigrees. The analytical method described herein can be used to screen causative genes for SLE and other complex diseases through pedigrees., Methods: For the first time, 24 lupus pedigrees were analyzed by combining whole exon sequencing and a variety of biological information tools including common-specific analysis, pVAAST (pedigree variant annotation, analysis and search tool), Exomiser (Combining phenotype and PPI associated analysis), and FARVAT (family based gene burden), and the causative genes of these families with lupus identified. Selected causative genes in peripheral-blood mononuclear cells (PBMCs) were evaluated by quantitative polymerase chain reaction (qPCR)., Results: Cell division cycle 27 (CDC27) was screened out by common-specific analysis and Exomiser causative gene screening. FARVAT analysis on these families detected only CDC27 at the extremely significant level (false discovery rate <0.05) by three family-based burden analyses (BURDEN, CALPHA, and SKATO). QPCR was performed to detect for CDC27 in the PBMCs of the SLE family patients, sporadic lupus patients, and healthy people. Compared with the healthy control group, CDC27 expression was low in lupus patients (familial and sporadic patients) ( P <0.05) and correlated with lupus activity indicators: negatively with C-reactive protein (CRP) ( P <0.05) and erythrocyte sedimentation rate ( P <0.05) and positively with complement C3 and C4 ( P <0.05). The CDC27 expression was upregulated in PBMCs from SLE patients with reduced lupus activity after immunotherapy ( P <0.05). Based on Receiver operating characteristic (ROC) curve analysis, the sensitivity and specificity of CDC27 in diagnosing SLE were 82.30% and 94.40%., Conclusion: The CDC27 gene, as found through WES combined with multiple analytical method may be a causative gene of lupus. CDC27 may serve as a marker for the diagnosis of SLE and is closely related to the lupus activity. We hope that the analytical method in this study will be used to screen causative genes for other diseases through small pedigrees, especially among non-close relatives., Competing Interests: Author LC was employed by Beijing Mygenostics co., LTD and author MZ was employed by Geneis (Beijing) Co., Ltd., Beijing, China. 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 Shang, Zhou, Chen, Chen, Li, Li, Cui, Zhang, Chen and Li.)

Importance: Atrial myopathy-characterized by alterations in left atrial (LA) function and size-is associated with ischemic stroke, independent of atrial fibrillation (AF). Electrocardiographic markers of atrial myopathy are associated with dementia, but it is unclear whether 2-dimensional echocardiographic (2DE)-defined LA function and size are associated with dementia., Objective: To examine the association of LA function and size with incident dementia., Design, Setting, and Participants: The Atherosclerosis Risk in Communities (ARIC) study is a community-based prospective cohort. An exploratory, retrospective analysis was conducted. ARIC centers are located in Forsyth County, North Carolina; Jackson, Mississippi; Washington County, Maryland; and suburban Minneapolis, Minnesota. For this analysis, visit 5 (2011-2013) served as the baseline. Participants without prevalent AF and stroke and who had 2DEs in 2011-2013 were included and surveilled through December 31, 2019., Exposures: LA function (reservoir strain, conduit strain, contractile strain, emptying fraction, passive emptying fraction, and active emptying fraction), and LA size (maximal and minimal volume index) as evaluated by 2DE., Main Outcomes and Measures: Dementia cases were identified using in-person and phone cognitive assessments, hospitalization codes, and death certificates. Cox proportional hazards models were used., Results: Among 4096 participants (mean [SD] age, 75 [5] years; 60% women; 22% Black individuals), 531 dementia cases were ascertained over a median follow-up of 6 years. Dementia incidence for the lowest LA quintile was 4.80 for reservoir strain, 3.94 for conduit strain, 3.29 for contractile strain, 4.20 for emptying fraction, 3.67 for passive emptying fraction, and 3.27 for active emptying fraction per 100 person-years. After full-model adjustments, there were statistically significant associations between measures of LA function and dementia; the hazard ratios (HRs) from the lowest vs highest quintile for reservoir strain were 1.98 (95% CI, 1.42-2.75); for conduit strain, 1.50 (95% CI, 1.09-2.06); for contractile strain, 1.57 (95% CI, 1.16-2.14); for emptying fraction, 1.87 (95% CI, 1.31-2.65); and for active emptying fraction, 1.43 (95% CI, 1.04-1.96). LA passive emptying fraction was not significantly associated with dementia (HR, 1.26 [95% CI, 0.93-1.71]). Dementia incidence for the highest LA maximal volume index quintile was 3.18 per 100 person-years (HR for highest vs lowest quintile, 0.77 [95% CI, 0.58-1.02]) and for the highest minimal volume index quintile was 3.50 per 100 person-years (HR for the highest vs lowest quintile, 0.95 [95% CI, 0.71-1.28]). Both measures were not significantly associated with dementia. These findings were robust to sensitivity analyses that excluded participants with incident AF or stroke., Conclusions and Relevance: In this exploratory analysis of a US community-based cohort, several echocardiographic measures of lower LA function were significantly associated with an increased risk of subsequent dementia. Measures of LA size were not significantly associated with dementia risk. These findings suggest that impaired LA function may be a risk factor associated with dementia.

Attempts to identify and prioritize functional DNA elements in coding and non-coding regions, particularly through use of in silico functional annotation data, continue to increase in popularity. However, specific functional roles can vary widely from one variant to another, making it challenging to summarize different aspects of variant function with a one-dimensional rating. Here we propose multi-dimensional annotation-class integrative estimation (MACIE), an unsupervised multivariate mixed-model framework capable of integrating annotations of diverse origin to assess multi-dimensional functional roles for both coding and non-coding variants. Unlike existing one-dimensional scoring methods, MACIE views variant functionality as a composite attribute encompassing multiple characteristics and estimates the joint posterior functional probabilities of each genomic position. This estimate offers more comprehensive and interpretable information in the presence of multiple aspects of functionality. Applied to a variety of independent coding and non-coding datasets, MACIE demonstrates powerful and robust performance in discriminating between functional and non-functional variants. We also show an application of MACIE to fine-mapping and heritability enrichment analysis by using the lipids GWAS summary statistics data from the European Network for Genetic and Genomic Epidemiology Consortium., Competing Interests: Declaration of interests X. Lin is a consultant of AbbVie Pharmaceuticals and Verify Life Sciences., (Copyright © 2022 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Objectives: This study aimed to investigate the biological impacts and possible mechanisms of a novel lncRNA, LncSIK1, in AML progression and retinoic acid-regulated AML cell development., Materials and Methods: The expression pattern of LncSIK1 was evaluated by qPCR and fluorescence in situ hybridization. CCK-8 assay, immunofluorescence, Wright-Giemsa staining, flow cytometry and Western blotting were performed to assess cell proliferation and differentiation. Bioluminescence imaging and H&E staining were used to detect AML progression in vivo. RNA or chromatin immunoprecipitation assays were conducted to measure the interaction of E2F1 and LncSIK1 or the LC3 and DRAM promoters. Autophagy was measured by transmission electron microscopy and Western blotting., Results: LncSIK1 was silenced in bone marrow mononuclear cells from AML patients compared with those from healthy donors. LncSIK1 strengthened the effect of retinoic acid in inducing cell differentiation and inhibiting cell proliferation in AML cells. Moreover, the silencing of LncSIK1 was critical to maintaining AML leukaemogenesis, as LncSIK1 enhancement retarded AML progression in vivo. Mechanistically, in NB4 cells, LncSIK1 recruited the E2F1 protein to the promoters of LC3 and DRAM and induced autophagy-dependent degradation of the oncoprotein PML-RARa. However, LncSIK1 blocked E2F1 expression and the E2F1-mediated transcription of LC3 and DRAM, thereby relieving aggressive autophagy in Molm13 cells., Conclusions: Taken together, these data indicated that LncSIK1 was an important regulator of AML development through regulating the E2F1/autophagy signalling pathway., (© 2022 The Authors. Cell Proliferation Published by John Wiley & Sons Ltd.)

A Gram-stain-negative, strictly aerobic, non-motile, rod-shaped bacterium, capable of producing poly-β-hydroxyalkanoate, designated DP3N28-2 T , was isolated from the sediment collected from Daya Bay, Guangdong, PR China. Optimal growth occurred at 37-40 °C, pH 6.0 and in the presence of 4 % NaCl. The 16S rRNA gene sequences analysis revealed that DP3N28-2 T showed highest similarities with Mameliella alba DSM 23384 T (98.3 %), Antarctobacter jejuensis 13-2-B6 T (97.2 %), Antarctobacter heliothermu s El-219 T (96.8 %), Maliponia aquimaris MM-10 T (96.7 %), Ponticoccus litoralis CL-GR66 T (96.4 %) and Aquicoccus porphyridii L1 8-17 T (96.1 %). The predominant fatty acids (>10 %) were summed feature 8 (C 18 : 1 ω6 c and/or C 18 : 1 ω7 c ; 72.1 %) and C 16 : 0 (11.0 %). The polar lipids contain phosphatidylethanolamine, phosphatidylmonomethylethanolamine, phosphatidylglycerol, one aminophosphlipid, one phospholipid and three unidentified lipids. The respiratory quinone was Q-10. The DNA G+C content was 63.0 mol% (data from the genome sequence). The estimated genome size was 5.12 Mb. The average nucleotide identity values between the DP3N28-2 T genome and the genome of M. alba was 81.1 %, while the digital DNA-DNA hybridization value was 23.4 %. The phenotypic, genotypic and chemotaxonomic differences between DP3N28-2 T and its phylogenetic relatives indicates that DP3N28-2 T should be regarded as representing a novel species of the genus Mameliella , for which the name Mameliella sediminis sp. nov. is proposed. The type strain is DP3N28-2 T (=MCCC 1K06218 T =KCTC 82804 T ).

Hydrogen peroxide (H 2 O 2 ) is used as a fuel and propellant in fuel cells and rockets due to its prominent oxidizing and combustion properties. In addition, hydrogen peroxide, as the energetic material with the simplest molecular structure, exhibits general detonation performance under external stimulation. Based on the first-principle method, we calculated the two crystal structure, electronic properties related to sensitivity closely, optical properties of pure hydrogen peroxide, and 48wt.% hydrogen peroxide (H 6 O 4 ) under pressure. We found that the band gaps of H 2 O 2 and H 6 O 4 become larger under pressure and the former is larger than the latter; neither has the tendency of metallization phase change. The added peak II of TDOS from H 6 O 4 compared with H 2 O 2 come from molecular H 2 O in crystal structure. The pressure-induced peak (peak 2 and peak II of TDOS from H 2 O 2 and H 6 O 4 ) splitting is caused by changes (stronger) in the intermolecular hydrogen bond environment in the crystal under pressure. The specific macroscopic optical properties have the characteristics of overall blue-shift under pressure, which is due to the blueshift of the conduction band and the increase of the band gap. We hope to provide some reference and guidance for deeper future research., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Nodular lymphoid hyperplasia (NLH) in the small intestine is a rare benign lesion characterized by multiple small nodules on the intestinal surface. Patients with terminal ileal NLH may experience long-term abdominal pain, diarrhea, and abdominal distension, among other symptoms. Supplementation with probiotics could mitigate these symptoms. NLH is linked to the immune system, and it may result from accumulation of plasma-cell precursors due to a maturational defect during the development of B lymphocytes. The intestinal microbiome plays an essential role in the immune system. Thus, we speculate that the gut flora plays a key role in terminal ileal NLH., Aim: To explore the correlation between intestinal flora and terminal ileal NLH., Methods: We collected mucosal biopsy samples that were obtained via colonoscopy from 15 patients with terminal ileal NLH (the test group) and 15 normal subjects (the control group). We subsequently performed 16S-rRNA gene amplicon sequencing of these samples, and the results were evaluated using alpha diversity, beta diversity and microbial composition analyses. The Phylogenetic Investigation of Communities by Reconstruction of Unobserved States was used to predict the metabolic pathways and orthologous groups according to the Kyoto Encyclopedia of Genes and Genomes database., Results: Compared with the control group, the terminal ileal NLH group showed an increased alpha diversity ( P < 0.05). The overall intestinal microbiota in the NLH group was significantly different from that of the control group ( P < 0.05), implying that there was the dysbiosis in the terminal ileal NLH patients. The relative abundance of phylum Bacteroidetes was significantly lower in the NLH group, while that of Patescibacteria and Campilobacterota was significantly higher. The genus Bacteroides was the dominant gut microbiota in both groups, but its abundance was significantly lower in the test group than it was in the control group. Conversely, the relative abundances of Haemophilus, Streptococcus, Pseudomonas, Actinomyces, TM7X, Fusobacterium nucleatum, Parvimonas, Granulicatella, Helicobacter , and the [ Eubacterium ] nodatum group were significantly higher in the test group than they were in the control group. In addition, several altered metabolic pathways, orthologous groups, and modules were found. For example, the Peptidoglycan biosynthesis and Aminoacyl tRNA biosynthesis were both increased in the test group., Conclusion: Maintaining the microbial balance and supplementing targeted protective bacteria could improve symptoms and potentially reduce the risk of lymphoma transformation in patients with terminal ileal NLH., Competing Interests: Conflict-of-interest statement: The authors declare that they have no competing interests., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: To explore the epidemiological characteristics and treatment outcomes of patients with hydrofluoric acid burns in hands. Methods: A retrospective observational study was conducted. The medical records of 229 patients with hydrofluoric acid burns in hands who were admitted to Zhejiang Quhua Hospital from January 2008 to December 2020 and met the inclusion criteria were collected. The following statistical data of patients were collected, including gender, age, type of affiliated enterprise, hydrofluoric acid mass fraction, injury site, total burn area, prehospital time, length of hospital stay, length of wound healing, whether hypocalcemia and hypomagnesemia occurred or not on admission, whether surgery intervention was performed or not, and whether scar sequelae occurred or not. Single factor and multivariate logistic regression analysis were used to screen out the risk factors impacting surgery intervention and scar sequelae of all the patients and patients whose hydrofluoric acid mass fraction was known. Single factor and multivariate linear regression analysis were used to screen out the risk factors impacting the length of wound healing of all the patients and patients whose hydrofluoric acid mass fraction was known. Results: The 229 patients included 206 males and 23 females, with the majority aged 30 to 50 years (139 patients). The type of affiliated enterprise of majority patients was non-fluorine chemical enterprise. The hydrofluoric acid mass fraction was known in only 91 patients, mainly medium. The majority injury site was in the middle and end of finger. The total burn area was below or equal to 1% total body surface area. The prehospital time was 19 (9, 29) h. The length of hospital stay was 2 (1, 7) d. The length of wound healing was 12 (8, 18) d. The proportions of hypocalcemia and hypomagnesemia were 0.9% (2/229) and 1.3% (3/229) on admission, respectively. Thirty-six patients had surgeries and 83 patients had scar sequelae. In 229 patients, single factor logistic regression analysis showed that both type of affiliated enterprise and prehospital time were the factors impacting surgery intervention (with odds ratio values of 7.86 and 51.35, respectively, 95% confidence intervals of 1.83-33.76 and 11.89-221.78, respectively, P <0.01) and scar sequelae of patients (with odds ratio values of 3.62 and 27.40, respectively, 95% confidence intervals of 1.76-7.43 and 13.25-56.68, respectively, P <0.01); multivariate logistic regression analysis showed that prehospital time was the independent risks factor impacting surgery intervention and scar sequelae of patients (with odds ratio values of 43.00 and 24.55, respectively, 95% confidence intervals of 9.89-187.03 and 11.78-51.16, respectively, P <0.01); single factor linear regression analysis showed that both type of affiliated enterprise and prehospital time were the factors impacting the length of wound healing of patients (with β values of 6.16 and 12.83, respectively, 95% confidence intervals of 3.38-8.93 and 10.72-14.93, respectively, P <0.01); multivariate linear regression analysis showed that both type of affiliated enterprise and prehospital time were the independent risk factors impacting the length of wound healing of patients (with β values of 2.81 and 12.16, respectively, 95% confidence intervals of 0.50-5.13 and 10.00-14.31, respectively, P <0.05 or P <0.01). In 91 patients whose hydrofluoric acid mass fraction was known, single factor logistic regression analysis showed that type of affiliated enterprise, hydrofluoric acid mass fraction (low and high), and prehospital time were all the factors impacting surgery intervention of patients (with odds ratio values of 9.10, 11.25, 10.69, and 0.04, respectively, 95% confidence intervals of 1.15-72.25, 1.39-90.93, 1.32-86.59, and 0.01-0.19, respectively, P <0.05 or P <0.01), type of affiliated enterprise, hydrofluoric acid mass fraction, and prehospital time were all the factors impacting scar sequelae of patients (with odds ratio values of 0.32, 0.21, and 36.80, respectively, 95% confidence intervals of 0.11-0.92, 0.06-0.73, and 11.03-122.79, respectively, P <0.05 or P <0.01); multivariate logistic regression analysis showed that both hydrofluoric acid mass fraction and prehospital time were the independent risk factors impacting surgery intervention of patients (with odds ratio values of 11.51 and 0.04, respectively, 95% confidence intervals of 1.22-108.26 and 0.01-0.25, respectively, P <0.05 or P <0.01), prehospital time was the independent risk factor impacting scar sequelae of patients (odds ratio=37.71, with 95% confidence interval of 9.97-142.69, P <0.01); single factor linear regression analysis showed that type of affiliated enterprise, hydrofluoric acid mass fraction (low and high), and prehospital time were all the factors impacting the length of wound healing of patients (with β values of 7.12, -5.63, -9.74, and 13.50, respectively, 95% confidence intervals of 2.43-11.81, -10.59--0.68, -14.78--4.70, and 10.14-16.86, respectively, P <0.05 or P <0.01); multivariate linear regression analysis showed that both hydrofluoric acid mass fraction and prehospital time were the independent risk factors impacting the length of wound healing of patients (with β values of -5.84 and 0.09, respectively, 95% confidence intervals of -10.59--1.08 and 0.05-0.12, respectively, P <0.05 or P <0.01). Conclusions: The majority of patients with hydrofluoric acid burns in hands are young and middle-aged males. Type of affiliated enterprise, hydrofluoric acid mass fraction and prehospital time are the risk factors that affect the treatment outcomes of patients with hydrofluoric acid burns in hands.

Background: Bark storage protein (BSP) plays an important role in seasonal nitrogen cycling in perennial deciduous trees. However, there is no report on the function of BSP in the perennial woody oil plant Jatropha curcas ., Methods: In this study, we identified six members of JcBSP gene family in J. curcas genome. The patterns, seasonal changes, and responses to nitrogen treatment in gene expression of JcBSP s were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Overexpression of JcBSP1 in transgenic Arabidopsis thaliana was driven by a constitutive cauliflower mosaic virus (CaMV) 35S RNA promoter., Results: JcBSP members were found to be expressed in various tissues, except seeds. The seasonal changes in the total protein concentration and JcBSP1 expression in the stems of J. curcas were positively correlated, as both increased in autumn and winter and decreased in spring and summer. In addition, the JcBSP1 expression in J. curcas seedlings treated with different concentrations of an NH 4 NO 3 solution was positively correlated with the NH 4 NO 3 concentration and application duration. Furthermore, JcBSP1 overexpression in Arabidopsis resulted in a phenotype of enlarged rosette leaves, flowers, and seeds, and significantly increased the seed weight and yield in transgenic plants., Competing Interests: The authors declare there are no competing interests., (©2022 Zhang et al.)

Background: Studies on temporomandibular disorder (TMD) severity in patient populations are scarce., Objectives: This study sought to compare the psychological states and oral health-related quality of life (OHRQoL) among patients with differing TMD severity., Methods: Adult patients (≥18 years old) with and without (controls) TMDs were recruited from the TMD/oro-facial pain centre and prosthodontics department, respectively. The presence and severity of TMDs were established with the Fonseca Anamnestic Index (FAI), and TMD diagnoses were confirmed with the Diagnostic Criteria for TMDs (DC/TMD). Psychological states and OHRQoL were examined with the Depression, Anxiety, Stress Scales-21 (DASS-21) and Oral Health Impact Profile for TMDs (OHIP-TMD). Data were subjected to chi-square, Kruskal-Wallis/Mann-Whitney U tests and Spearman's correlation (α = .05)., Results: A total of 961 participants with a mean age of 32.99 ± 13.14 years (71.19% women) were assessed. Frequencies of the various TMD categories were as follows: no TMD/controls (12.07%), mild TMD (24.56%), moderate TMD (40.37%) and severe TMD (23.00%). The three most common TMD-related symptoms were TMJ noises, mouth opening difficulty and muscle pain. Participants with moderate/severe TMD presented a higher proportion of intra-articular and/or combined disorders. They reported significantly higher levels of depression, anxiety, stress and poorer OHRQoL than their counterparts with no/mild TMD (p < .001). Moderate-to-strong correlations were observed between FAI and DASS-21/OHIP-TMD scores (rs = 0.42-0.72)., Conclusions: Patients with moderate/severe TMD had significantly higher levels of psychological disturbance and poorer OHRQoL. As OHRQoL and psychological states are correlated, psychological well-being must be considered when managing patients with moderate/severe TMDs., (© 2021 John Wiley & Sons Ltd.)

Purpose: This study was carried out to evaluate the value of comfort nursing in light curing resin-treated dental caries by means of patient satisfaction survey., Methods: One hundred and twenty-eight cariogenic patients, who were treated from January 2017 to December 2017 in Shanghai Ninth People's Hospital, were enrolled and randomly assigned as experimental group and control group, respectively(n=64). Cariogenic lesions were treated with light-cured resin, patients in the control group received conventional four-handed operation nursing, while patients in the experimental group received modified comfortable nursing throughout the entire treatment course. The self-designed satisfaction questionnaires were issued, and the patients were required to fill them out after the treatment and nursing were definitely completed. The designed questionnaire was divided into two major parts, including nursing care and nursing operation, which was further subdivided into 10 detailed scoring items. The satisfaction survey of nursing was analyzed between two groups statistically to evaluate the effort of comfort nursing using SPSS 19.0 software package., Results: No significant differences in the treatment environment was observed between the two groups(P＞0.05), while upgraded satisfaction were observed in patients from the experimental group compared to those from the control group on the aspects of nursing care, namely, appearance, service attitude, explanation and health knowledge promotion(P＜0.05). Among the five scoring standards of nursing operation, which was consist of timely initiative nursing, position nursing, eye nursing, effective nursing and nursing procedures, the satisfaction scores from the experimental group were significantly higher than those from the control group(P＜0.05). The total collected data demonstrated that the overall satisfaction of the experimental group was significantly improved compared to that of the control group (94% vs 75%, P＜0.01)., Conclusions: Comfort nursing not only strengthens the professionalism of oral operation, but also improves the patient's experience, facilitating to promote the harmony between doctors and patients.

Randomized clinical trials offer the highest-quality data for modifying clinical practice. Results of a phase III randomized trial of nonmyeloablative transplantation for adults with high-risk hematologic malignancies with 2 umbilical cord blood (UCB) units (n = 183) or HLA-haploidentical relative bone marrow (Haplo-BM; n = 154) revealed a 2-year progression-free survival (PFS) of 41% after Haplo-BM transplantation and 35% after 2-unit UCB transplantation (P = .41), with overall survival (OS) of 57% and 46%, respectively (P = .04). We sought to examine the generalizability of BMT CTN 1101 to a contemporaneous cohort beyond the trial's prespecified 2-year outcomes. All transplantations were performed between June 2012 and June 2018 in the United States. We hypothesized that the results of a rigorous phase III randomized trial would be generalizable. Changes in graft selection for HLA-haploidentical relative transplantation during the trial period allowed comparison of outcomes after transplantation with Haplo-BM with those after haploidentical peripheral blood (Haplo-PB). The trial's broad eligibility criteria were applied to the data source of the Center for International Blood and Marrow Transplant Research to select nontrial subjects. Extended follow-up of trial subjects was obtained from this data source. Three separate analyses were performed: (1) trial subjects beyond the trial's 2-year endpoint; (2) comparison of trial subjects with a contemporaneous cohort of nontrial subjects (195 2-unit UCB, 358 Haplo-BM, and 403 Haplo-PB); and (3) comparison of nontrial subjects by donor and graft type. Multivariate analyses were performed using Cox proportional hazards models for comparison of outcomes by treatment groups. With longer follow-up of the trial cohorts, 5-year PFS (37% versus 29%; P = .08) and OS (42% versus 36%; P = .06) were not significantly different between the treatment groups. We then compared the trial results with outcomes of comparable real-world transplantations. Five-year OS did not differ between trial and nontrial 2-unit UCB transplantations (36% versus 41%; P = .48) or between trial and nontrial Haplo-BM transplantations (42% versus 47%; P = .80), confirming generalizability. The randomized trial did not accrue as planned and therefore lacked the statistical power to detect a 15% difference in PFS. With substantially larger numbers of nontrial Haplo-BM transplantations, 5-year survival was higher after nontrial Haplo-BM compared with trial 2-unit UCB (47% versus 36%; P = .012). Nontrial patients who underwent Haplo-PB transplantation had higher 5-year survival (54%) compared with trial Haplo-BM (hazard ratio [HR], 0.76; P = .044) and nontrial Haplo-BM (HR, 0.78; P = .026). Similarly, survival was better after Haplo-PB compared with trial UCB (HR, 0.57; P < .0001) and nontrial UCB (HR, 0.63; P = .0002). When considering alternative donor low-intensity conditioning regimen transplantation, a haploidentical relative is preferred, and PB is the preferred graft source., (Copyright © 2021 The American Society for Transplantation and Cellular Therapy. All rights reserved.)

Pollen tube growth and penetration in female tissues are essential for the transfer of sperm to the embryo sac during plant pollination. Despite its importance during pollination, little is known about the mechanisms that mediate pollen tube growth in female tissues. In this study, we identified an Arabidopsis thaliana pollen/pollen tube-specific gene, SKU5-SIMILAR 13 (SKS13), which was critical for the growth of pollen tubes in the transmitting tract. The SKS13 protein was distributed throughout the cytoplasm and pollen tube walls at the apical region. In comparison with wild-type pollen tubes, those of the sks13 mutants burst more frequently when grown in vitro. Additionally, the growth of sks13 pollen tubes was retarded in the transmitting tract, thereby resulting in decreased male fertility. The accumulation of pectin and cellulose in the cell wall of sks13 pollen tubes was altered, and the content of jasmonic acid (JA) in sks13 pollen was reduced. The pollen tubes treated with an inhibitor of JA biosynthesis grew much more slowly and had an altered distribution of pectin, which is similar to the pollen tube phenotypes of the SKS13 mutation. Our results suggest that SKS13 is essential for pollen tube growth in the transmitting tract by mediating the biosynthesis of JA that modifies the components of pollen tube cell walls., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Human immunodeficiency virus (HIV) is the most extensively researched human pathogen. Despite this massive scientific endeavour, several fundamental viral processes remain enigmatic. One such critical process is uncoating-the event that releases the viral genome from the proteinaceous shell of the capsid during infection. While this process is conceptually simple, the molecular underpinnings, timing, regulation, and cellular location of uncoating remain contentious. This review describes the hurdles that have limited our understanding in this area and presents recently deployed in vitro and in cellulo techniques that have been developed expressly with the aim of directly visualising capsid uncoating at the single-particle level and understanding the mechanics behind this essential aspect of HIV infection., Competing Interests: Conflict of interestThe authors declare no competing interests., (© International Union for Pure and Applied Biophysics (IUPAB) and Springer-Verlag GmbH Germany, part of Springer Nature 2021.)