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An-Ran Shen,1 Xiao-Xiao Jin,2 Tao-Tao Tang,1 Yan Ding,2 Xiao-Tao Liu,2 Xin Zhong,1 Yan-Dan Wu,2 Xue-Lian Han,3 Guang-Yu Zhao,3 Chuan-Lai Shen,2 Lin-Li Lv,1 Bi-Cheng Liu1 1Institute of Nephrology, Zhongda Hospital, Medical School of Southeast University, Nanjing, 210009, People’s Republic of China; 2Department of Microbiology and Immunology, Medical School of Southeast University, Nanjing, 210009, People’s Republic of China; 3State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, People’s Republic of ChinaCorrespondence: Lin-Li Lv; Bi-Cheng Liu, Institute of Nephrology, Zhongda Hospital, Medical School of Southeast University, Nanjing, 210009, People’s Republic of China, Tel +862583272512, Email lvlinli@seu.edu.cn; liubc64@163.comPurpose: Current vaccines for the SARS-CoV-2 virus mainly induce neutralizing antibodies but overlook the T cell responses. This study aims to generate an exosomal vaccine carrying T cell epitope peptides of SARS-CoV-2 for the induction of CD8+ T cell response.Methods: Thirty-one peptides presented by HLA-A0201 molecule were conjugated to the DMPE-PEG-NHS molecules, and mixed with DSPE-PEG to form the peptide-PEG-lipid micelles, then fused with exosomes to generate the exosomal vaccine, followed by purification using size-exclusion chromatography and validation by Western blotting, liquid nuclear magnetic resonance (NMR) test and transmission electron microscopy. Furthermore, the exosomal vaccine was mixed with Poly (I:C) adjuvant and subcutaneously administered for three times into the hybrid mice of HLA-A0201/DR1 transgenic mice with wild-type mice. Then, the epitope-specific T cell responses were detected by ex vivo ELISPOT assay and intracellular cytokine staining.Results: The exosomal vaccine was purified from the Peak 2 fraction of FPLC and injected into the hybrid mice for three times. The IFN-γ spot forming units and the frequencies of IFN-γ+/CD8+ T cells were 10– 82-fold and 13– 65-fold, respectively, higher in the exosomal vaccine group compared to the Poly (I:C) control group, without visible organ toxicity. In comparison with the peptides cocktail vaccine generated in our recent work, the exosomal vaccine induced significantly stronger T cell response.Conclusion: Exosomal vaccine loading T cell epitope peptides of SARS-CoV-2 virus was initially generated without pre-modification for both peptides and exosomes, and elicited robust CD8+ T cell response in HLA-A transgenic mice.Graphical Abstract: Keywords: the severe acute respiratory syndrome coronavirus-2, exosomal vaccine, T cell, epitope, human leukocyte antigen-A

α-Aminonitriles are not only broadly useful building blocks but also structural motifs in bioactive molecules. The Strecker reaction is one of the most widely used methods for α-aminonitrile synthesis. However, a severe drawback in Strecker reactions is the required use of a stoichiometric amount of toxic cyanation reagents. Thus, the development of a greener and widely applicable method for the synthesis of aminonitriles from readily available starting materials presents an important yet unmet challenge. We developed a general and new method for the synthesis of aminonitriles from readily available aminoacetonitrile. This method utilized off-the-shelf ammonium salts as catalysts, tolerated air and moisture, and avoided the use of cyanation reagents, which rendered it a greener alternative to the widely practiced Strecker reaction approach. We further illustrated that chiral ammonium-catalyzed asymmetric reactions of N -arylidene aminoacetonitriles could provide chiral α-tertiary and α-quaternary aminonitriles and α-aminonitriles bearing two continuous stereocenters.

Background: A sclerosing epithelioid fibrosarcoma (SEF) is a rare malignant fibroblastic soft tissue tumor that rarely occurs in intra-abdominal organs. A case of a SEF in the pancreatic head is reported herein, including its clinical manifestations, preoperative imaging features, gross specimen and pathological findings., Case Summary: A 33-year-old male patient was admitted to Peking Union Medical College Hospital in December 2023 due to a one-year history of intermittent upper abdominal pain and the discovery of a pancreatic mass. The patient underwent an enhanced computed tomography scan of the abdomen, which revealed a well-defined, round mass with clear borders and calcifications in the pancreatic head. The mass exhibited progressive, uneven mild enhancement, measuring approximately 6.6 cm × 6.3 cm. The patient underwent laparoscopic pylorus-preserving pancreaticoduodenectomy. Postoperative pathological examination revealed that the lesion was consistent with a SEF. At the 3-month postoperative follow-up, the patient did not report any short-term complications, and there were no signs of tumor recurrence., Conclusion: SEFs are rare malignant fibrous soft tissue tumors. SEFs rarely develop in the pancreas, and its preoperative diagnosis depends on imaging findings, with confirmation depending on pathological examination and immunohistochemistry. Currently, only four cases of pancreatic SEF have been reported in studies written in English. This case is the first reported case of a pancreatic SEF by a clinical physician., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Analysis of correlation between the early testable phenotypes of piglets and the final performance of pigs can serve the early selection for breeding. The objectives of this study were to estimate the genetic parameters for birth weight (BtW), age (AGE) and backfat thickness (BF) up to 115 kg BW and to analyse the relationships among these three traits, and to estimate the accuracy of using BtW to predict estimated breeding values (EBVs) of AGE and BF in Landrace and Duroc pigs. Data on 26 614 Landrace and 19 984 Duroc pigs, born between 2001 and 2018, were collected from the core breeding group of a farm. All pigs were recorded for phenotypes including BtW, AGE and BF. The factors affecting these three traits were analysed using R v4.2.0 Software. The population genetic parameters and breeding values of three traits were estimated by using a multitrait animal model based on AI plate of DMU software. Heritabilities for BtW, AGE and BF were moderate to high for Landrace (0.437, 0.282and 0.137, respectively) and Duroc breeds (0.369, 0.279 and 0.148). BtW was genetically correlated with AGE and BF in Landrace (-0.213, 0.037) and Duroc (-0.214, 0.025). AGE was negatively genetically correlated with BF in both Landrace (-0.036) and Duroc (-0.057) pigs. The heritability of BtW, AGE and BF of Landrace pigs and Duroc pigs were 0.148, 0.182 and 0.075 and 0.168, 0.159 and 0.120, respectively, by taking into account of the litter effect. BtW was genetically correlated with AGE and BF in Landrace (-0.094, 0.002) and Duroc (-0.199, -0.052). AGE was negatively genetically correlated with BF in both Landrace (-0.034) and Duroc (-0.153) pigs. The variances between total individual BtW and AGE and BF were then used to predict the EBV of AGE and BF for individuals with AGE or BF phenotypes missing under 10-fold cross-validation. Prediction accuracy was calculated as the Kendall tau-b correlation coefficient between EBVs and EBVs via 10-fold cross-validation. Prediction accuracy for AGE and BF was 0.655 and 0.611 in Landrace, 0.665 and 0.617 in Duroc. After incorporation of the litter effect, the prediction accuracy for AGE and BF increased to 0.690 and 0.665 in Landrace and to 0.705 and 0.649 in Duroc. So, the EBV of AGE and BF phenotypes missing individuals could be predicted by using the available phenotypic data and the easily measured BtW, and litter effect could boost the accuracy of prediction., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: The purpose of this study was to compare safety and efficacy outcomes between immediate breast reconstruction (IBR) and mastectomy alone in locally advanced breast cancer patients., Methods: We conducted a comprehensive literature search of PUBMED, EMBASE, and Cochrane databases. The primary outcomes evaluated were overall survival, disease-free survival, and local recurrence. The secondary outcome was the incidence of surgical complications. All data were analyzed using Review Manager 5.3., Results: Sixteen studies, involving 15,364 participants were included in this meta-analysis. Pooled data demonstrated that patients underwent IBR were more likely to experience surgical complications than those underwent mastectomy alone (HR: 3.96, 95%CI [1.07,14.67], p = 0.04). No significant difference was found in overall survival (HR: 0.94, 95%CI [0.73,1.20], p = 0.62), disease-free survival (HR: 1.03, 95%CI [0.83,1.27], p = 0.81), or breast cancer specific survival (HR: 0.93, 95%CI [0.71,1.21], p = 0.57) between IBR group and Non-IBR group., Conclusions: Our study demonstrates that IBR after mastectomy does not affect the overall survival and disease-free survival of locally advanced breast cancer patients. However, IBR brings with it a nonnegligible higher risk of complications and needs to be fully evaluated and carefully decided., (© 2024. The Author(s).)

Background: Function-preserving pancreatectomy can improve the long-term quality of life of patients with benign or low-grade malignant tumors, such as intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms. However, there is limited literature on laparoscopic spleen-preserving total pancreatectomy (L-SpTP) due to technical difficulties., Case Summary: Patient 1 was a 51-year-old male diagnosed with IPMN based on preoperative imaging, showing solid nodules in the pancreatic head and diffuse dilation of the main pancreatic duct with atrophy of the distal pancreas. We performed L-SpTP with preservation of the splenic vessels, and the postoperative pathology report revealed IPMN with invasive carcinoma. Patient 2 was a 60-year-old male with multiple cystic lesions in the pancreatic head and body. L-SpTP was performed, and intraoperatively, the splenic vein was injured and required ligation. Postoperative pathology revealed a mucinous cystic tumor of the pancreas with low-grade dysplasia. Both patients were discharged on postoperative day 7, and there were no major complications during the perioperative period., Conclusion: We believe that L-SpTP is a safe and feasible treatment for low-grade malignant pancreatic tumors, but more case studies are needed to evaluate its safety, efficacy, and long-term outcomes., Competing Interests: Conflict-of-interest statement: There are no competing interests., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Culture-dependent and metagenomic binning techniques were employed to gain an insight into the diversification of gut bacteria in Rhinopithecius bieti, a highly endangered primate endemic to China. Our analyses revealed that Bacillota_A and Bacteroidota were the dominant phyla. These two phyla species are rich in carbohydrate active enzymes, which could provide nutrients and energy for their own or hosts' survival under different circumstances. Among the culturable bacteria, one novel bacterium, designated as WQ 2009 T , formed a distinct branch that had a low similarity to the known species in the family Sphingobacteriaceae, based on the phylogenetic analysis of its 16S rRNA gene sequence or phylogenomic analysis. The ANI, dDDH and AAI values between WQ 2009 T and its most closely related strains S. kitahiroshimense 10C T , S. pakistanense NCCP-246 T and S. faecium DSM 11690 T were significantly lower than the accepted cut-off values for microbial species delineation. All results demonstrated that WQ 2009 T represent a novel genus, for which names Rhinopithecimicrobium gen. nov. and Rhinopithecimicrobium faecis sp. nov. (Type strain WQ 2009 T  = CCTCC AA 2021153 T  = KCTC 82941 T ) are proposed., (© 2024. The Author(s).)

Multiple cell death pathways are involved in neuronal death in ischemic stroke (IS). However, the role of different cell death pathways in different cell types has not been elucidated. By analyzing three single-nucleus RNA sequencing (snRNA-seq) data of IS, we first found that a variety of programmed cell death (PCD) -related genes were significantly changed in different cell types. Based on machine learning and virtual gene knockout, we found that ferroptosis related genes, ferritin heavy chain 1 (Fth1) and ferritin light chain (Ftl1), play a key role in IS. Ftl1 and Fth1 can promote microglia activation, as well as the production of inflammatory factors and chemokines. Cell communication analysis showed that activated microglia could enhance chemotactic peripheral leukocyte infiltration, such as macrophages and neutrophils, through Spp1-Cd44 and App-Cd74 signaling, thereby aggravating brain tissue damage. Furthermore, real-time quantitative polymerase chain reaction (RT-qPCR) showed that P2ry12 and Mef2c were significantly decreased in oxygen-glucose deprivation (OGD) group, while Ftl1, Fth1, Apoe, Ctsb, Cd44 and Cd74 were significantly increased in OGD group. Collectively, our findings suggested targeted therapy against microglia Ftl1 and Fth1 might improve the state of microglia, reduce the infiltration of peripheral immune cells and tissue inflammation, and then improve the ischemic brain injury in mouse., Competing Interests: The authors declare that they have no conflict of interest., (© 2024 The Authors. Published by Elsevier Ltd.)

Background: Tumor genetic anomalies and immune dysregulation are pivotal in the progression of multiple myeloma (MM). Accurate patient stratification is essential for effective MM management, yet current models fail to comprehensively incorporate both molecular and immune profiles., Methods: We examined 776 samples from the MMRF CoMMpass database, employing univariate regression with LASSO and CIBERSORT algorithms to identify 15 p53-related genes and six immune cells with prognostic significance in MM. A p53-TIC (tumor-infiltrating immune cells) classifier was constructed by calculating scores using the bootstrap-multicox method, which was further validated externally (GSE136337) and through ten-fold internal cross-validation for its predictive reliability and robustness., Results: The p53-TIC classifier demonstrated excellent performance in predicting the prognosis in MM. Specifically, patients in the p53 low /TIC high subgroup had the most favorable prognosis and the lowest tumor mutational burden (TMB). Conversely, those in the p53 high /TIC low subgroup, with the least favorable prognosis and the highest TMB, were predicted to have the best anti-PD1 and anti-CTLA4 response rate (40 %), which can be explained by their higher expression of PD1 and CTLA4. The three-year area under the curve (AUC) was 0.80 in the total sample., Conclusions: Our study highlights the potential of an integrated analysis of p53-associated genes and TIC in predicting prognosis and aiding clinical decision-making in MM patients. This finding underscores the significance of comprehending the intricate interplay between genetic abnormalities and immune dysfunction in MM. Further research into this area may lead to the development of more effective treatment strategies., Competing Interests: 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., (© 2024 The Authors. Published by Elsevier Ltd.)

Pharmaceuticals and biologically active natural products usually contain multiple stereocenters. The development of catalytic asymmetric reactions for the direct construction of complex motifs containing three nonadjacent stereocenters is a particularly important and formidable challenge. In this paper, we report an unprecedented method for the direct asymmetric construction of complex chiral amines with 1,3,5- or 1,3,4-stereocenters from readily available achiral and racemic starting materials. The reaction was made possible by the development of highly efficient chiral ammonium catalysts that serve three distinct functions: promoting efficient kinetic resolution by chiral recognition of racemic electrophiles, promoting asymmetric C-C bond forming reactions by recognizing enantiotropic faces of achiral nucleophiles, and mediating a highly stereoselective protonation of carbanions. Using these trifunctional catalysts, the reaction of imines and tulipane derivatives proceeded in a highly regio-, chemo-, and stereoselective manner to produce synthetically useful yields of complex chiral amines. We believe that trifunctional catalysis can be applied in a variety of asymmetric transformations for the streamlined asymmetric synthesis of complex chiral molecules with multiple stereocenters.

The incidence of allergic rhinitis (AR) is increasing year by year, especially in children. AR not only affects the growth, development, life and learning of children but also causes huge economic and social burdens. This study explores the impact of individual factors such as genetic polymorphisms, epigenetics, inflammatory response mechanisms, and microecological influence mechanisms on children's AR. It also reviews the impact of external factors such as allergenic factors, ambient air pollutants, infection and immunity factors, and climate and climate change on the disease, with the aim of improving understanding of AR in children and providing a basis for its prevention and treatment.

A novel Gram-positive strain WQ 127069 T that was isolated from the soil of Baima Snow Mountain, a habitat of highly endangered Yunnan snub-nosed monkeys ( Rhinopithecus bieti ), was subjected to a polyphasic taxonomic study. Phylogenetic analysis based on the 16S rRNA gene sequences showed that the isolate belongs to the genus Paenibacillus , showing 98.4 and 96.08 % sequence similarity to the type strains Paenibacillus periandrae PM10 T and Paenibacillus foliorum LMG 31456 T , respectively. The G+C content of the genomic DNA of strain WQ127069 T was 45.6 mol%. The predominant isoprenoid quinone was MK-7, and meso -diaminopimelic acid was present in peptidoglycan. The major cellular fatty acids were antiiso-C 15 : 0 , iso-C 15 : 0 and C 16 : 0 . The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol and phosphatidylmonomethylethanolamine. The whole genome average nucleotide identity and digital DNA-DNA hybridization values between strain WQ 127069 T and strain PM10 T were 93.2 and 52.5 %, respectively. Growth occurred at 5-40 °C (optimally at 20-35 °C), pH 6-8 (optimally at pH7.0) and with 0.5-2 % (w/v) NaCl (optimally at 0.5 %). On the basis of the taxonomic evidence, a novel species, Paenibacillus baimaensis sp. nov., is proposed. The type strain is WQ 127069 T (=KCTC 43480 T =CCTCC AB 2022381 T ).

Equisetin, a bioactive compound of marine origin, offers compelling inhibitory properties against HIV-1 transcriptase. To gain comprehensive insights into the interaction of Equisetin with human serum albumin (HSA), we utilized a multipronged approach involving spectroscopy, isothermal titration calorimetry (ITC) and molecular docking. Our fluorescence analyses confirmed that the interaction between Equisetin and HSA results in a significant quenching of HSA's fluorescence, primarily achieved through a dynamic mechanism aided by hydrogen bonding and van der Waals forces. Isothermal titration calorimetry (ITC) measurements revealed an impressive binding affinity of Equisetin for HSA, quantified to be 4.3 × 10 7 mol L -1 . Molecular docking studies illustrated that Equisetin binds at site III of HSA, with specific amino acid residues, GLN-104 and LYS-106, playing a pivotal role. Further, our study discovered that the interaction induces slight unfolding of HSA's polypeptide chain and significant alterations in its secondary structure, thereby triggering the exposure of previously concealed hydrophobic regions. This comprehensive study enhances our understanding of Equisetin's interaction with serum proteins, potentially influencing its pharmacokinetics and pharmacodynamics, and opening avenues for future research and therapeutic applications., 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 © 2023 Elsevier B.V. All rights reserved.)

Objective: In this study, we aimed to investigate whether age first had sexual intercourse (AFSI) and lifetime number of sexual partners (LNSP) have a direct causal effect on cervical cancer by Mendelian randomization (MR) analysis., Methods: Four approaches were used for MR Analysis, including MR-Egger, weighted method, weighted median, and inverse variance weighted (IVW). MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) as well as MR-Egger regression analysis were conducted to detect whether there was pleiotropy between IVs and outcome, and the outlier SNPs can be detected by MR-PRESSO. The presence or absence of heterogeneity among IVs was suggested according to Cochran's Q statistic. Leave-one-out sensitivity analysis was performed to identify and remove SNPs which could independently change the results. We corrected the results using Bonferroni correction., Results: From the results of IVW, AFSI had a negative effect on cervical cancer (OR = 0.996, 95 % CI: 0.995, 0.998  P  = 1.70E-07), which still persisted after Bonferroni correction. However, no causal effect of LNSP on cervical cancer was found according to the IVW results (OR = 1.003, 95 % CI: 1.000, 1.007, P  = 0.071). From the results of MR-PRESSO and MR-Egger, no SNP with horizontal pleiotropy between cervical cancer was detected and no SNP was identified as an outlier SNP. Cochran's Q statistic suggested that no heterogeneity existed among IVs of AFSI and LNSP. According to Leave-one-out analysis, the results of MR did not change after excluding any single IV., Conclusion: This MR study reveals that early AFSI has a causal effect on cervical cancer., Competing Interests: 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., (© 2023 The Authors. Published by Elsevier Ltd.)

Objective: To analyze the ultrasound characteristics of small bowel volvulus among adults and to investigate the value of ultrasound in the diagnosis of small bowel volvulus. Methods: Totally 34 adults with small bowel volvulus confirmed by clinical diagnosis or surgery and who underwent ultrasound examination at Peking Union Medical College Hospital from August 2017 to October 2022 were enrolled, including 19 males and 15 females, aged (55.0±21.8) years (range: 19 to 94 years). The clinical characteristics, CT images and ultrasound images of the patients were retrospectively reviewed, and the ultra, sound features of small bowel volvulus and its diagnostic efficacy were analyzed. Results: Abdominal pain was the typical clinical symptom of all patients. Other symptoms included 21 cases of abdominal distension, 19 cases of nausea and vomiting, and 13 cases of cessation of passage of stool or flatus. Eight patients had signs of peritonitis and 22 patients had abnormal bowel sounds. Twenty patients had a history of abdominal surgery. Twenty-seven patients underwent surgery for intestinal obstruction, and the remaining 7 patients improved after conservative treatment. All cases were evaluated by ultrasound, 11 cases showed a "whirl sign" and were diagnosed as small bowel volvulus, the diagnostic accuracy rate was 32.4% (11/34), ultrasound simultaneously diagnosed intestinal obstruction in 21 cases, 17 cases of abdominal effusion, 4 cases of intestinal wall thickening, 2 cases of abdominal mass, 1 case of intussusception, 1 case of right sided inguinal hernia. CT and ultrasound had a consistent positive discovery in 88.2% (30/34) of all the patients. Conclusion: Ultrasound is valuable in the diagnosis of small bowel volvulus and the evaluation of complications.

A young man with a history of thrombocytopenia for seven years presented with splenomegaly and fever and rapidly evolved to disseminated intravascular coagulation (DIC) and hemorrhagic shock. Spontaneous rupture of the spleen was diagnosed. The critical patient underwent an emergency splenectomy. Pathological examination revealed splenic peliosis, an extremely rare disease with unknown etiology and pathogenesis. Despite the high mortality rate due to spontaneous splenic rupture with DIC, the patient was successfully treated and the details of the case are presented in this report.

Background: Delayed gastric emptying (DGE) remains one of the major complications after pancreaticoduodenectomy (PD), with discrepant reports of its contributing factors. This study aimed to develop a nomogram to identify potential predictors and predict the probability of DGE after PD., Methods: This retrospective study enrolled 422 consecutive patients who underwent PD from January 2019 to December 2021 at our institution. The LASSO algorithm and multivariate logistic regression were performed to identify independent risk and protective factors associated with clinically relevant delayed gastric emptying (CR-DGE). A nomogram was established based on the selected variables. Then, the calibration curve, ROC curve, decision curve analysis (DCA), and clinical impact curve (CIC) were applied to evaluate the predictive performance of our model. Finally, an independent cohort of 45 consecutive patients from January 2022 to March 2022 was enrolled to further validate the nomogram., Results: Among 422 patients, CR-DGE occurred in 94 patients (22.2%). A previous history of chronic gastropathy, intraoperative plasma transfusion ≥ 400 ml, end-to-side gastrointestinal anastomosis, intra-abdominal infection, incisional infection, and clinically relevant postoperative pancreatic fistula (CR-POPF) were identified as risk predictors. Minimally invasive pancreaticoduodenectomy (MIPD) was demonstrated to be a protective predictor of CR-DGE. The areas under the curve (AUCs) were 0.768 (95% CI, 0.706-0.830) in the development cohort, 0.766 (95% CI, 0.671-0.861) in the validation cohort, and 0.787 (95% CI, 0.633-0.940) in the independent cohort. Then, we built a simplified scale based on our nomogram for risk stratification., Conclusions: Our study identified seven predictors and constructed a validated nomogram that effectively predicted CR-DGE for patients who underwent PD., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Catalytic asymmetric cross-coupling of imines constitutes a particularly desirable method for the synthesis of chiral vicinal diamines directly from readily available achiral precursors. The potential of this method lies in the possibility of utilizing a variety of imines as reacting partners. However, the realization of highly stereoselective cross-coupling of two different imines proved to be a formidable challenge. Herein we report an unprecedented catalytic asymmetric cross-coupling reaction that tolerates a variety of ketimines and aldimines as nucleophiles and electrophiles, respectively. The realization of this reaction resulted from the development of a new chiral ammonium catalyst, which was guided by insights from studies of catalyst-substrate interactions. With a 0.5 mol % loading of an organocatalyst, this reaction proceeded in a highly diastereo- and enantioselective manner to afford a diverse range of chiral vicinal diamines as nearly single stereoisomers. This catalytic reaction establishes a new approach for the asymmetric synthesis of chiral vicinal diamines.

Objectives: Excessive accumulation of adipose tissue may accelerate brain aging, but the underlying mechanisms are poorly understood. Several adiposity indices were proposed to assess obesity, while their linkage with brain health in older adults remained unclear. Here we aimed to examine the associations of adiposity indices with global and regional cerebral blood flow (CBF) in older adults, while considering insulin resistance., Design: This was a cross-sectional population-based study that included older adults derived from the baseline participants in the ongoing Multimodal Interventions to Delay Dementia and Disability in rural China (MIND-China) study., Setting and Participants: The study included 103 Chinese rural-dwelling older adults (age≥60 years; 69.9% women) who underwent brain magnetic resonance imaging scans., Methods: We estimated eight adiposity indices based on anthropometric measures. We automatically quantified global and regional CBF using the arterial spin labeling scans. Insulin resistance was assessed using the triglyceride-glucose index and then dichotomized into high and low levels according to the median. Data were analyzed using general linear model and voxel-wise analysis., Results: Of the eight examined adiposity indices, only higher waist-to-height ratio (WHtR) and body roundness index (BRI) were associated with reduced global CBF (multivariable-adjusted β-coefficients and 95%CI: -1.76; -3.25, -0.27 and -1.77; -3.25, -0.30, respectively) and hypoperfusion in bilateral middle temporal gyri, angular gyri and superior temporal gyri, left middle cingulum and precuneus (P<0.05). There were statistical interactions of WHtR and BRI with levels of insulin resistance on CBF, such that the significant associations of higher WHtR and BRI with lower global and regional CBF existed only in people with high insulin resistance (P<0.05)., Conclusion: Higher WHtR and BRI are associated with cerebral hypoperfusion in older adults, especially in people with high insulin resistance. This may highlight the pathological role of visceral fat in vascular brain aging., Competing Interests: All authors declare no conflicts of interest.

The rapidly growing concern of marine microplastic pollution has drawn attentions globally. Microplastic particles are normally subjected to visual characterization prior to more sophisticated chemical analyses. However, the misidentification rate of current visual inspection approaches remains high. This study proposed a state-of-the-art deep learning-based approach, Mask R-CNN, to locate, classify, and segment large marine microplastic particles with various shapes (fiber, fragment, pellet, and rod). A microplastic dataset including 3000 images was established to train and validate this Mask R-CNN algorithm, which was backboned by a Resnet 101 architecture and could be tuned in less than 8 h. The fully trained Mask R-CNN algorithm was compared with U-Net in characterizing microplastics against various backgrounds. The results showed that the algorithm could achieve Precision = 93.30%, Recall = 95.40%, F1 score = 94.34%, AP bb (Average precision of bounding box) = 92.7%, and AP m (Average precision of mask) = 82.6% in a 250 images test dataset. The algorithm could also achieve a processing speed of 12.5 FPS. The results obtained in this study implied that the Mask R-CNN algorithm is a promising microplastic characterization method that can be potentially used in the future for large-scale surveys., 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 Ltd. All rights reserved.)

The nonselective membrane disruption of antimicrobial peptides (AMPs) helps in combating the antibacterial resistance. But their overall positive charges lead to undesirable hemolysis and toxicity toward normal living cells, as well as the rapid clearance from blood circulation. In consequence, developing smart AMPs to optimize the antimicrobial outcomes is highly urgent. Relying on the local acidity of microbial infection sites, in this work, we designed an acidity-triggered charge reversal nanotherapeutics with adaptable geometrical morphology for bacterial targeting and optimized therapy. C 16 -A 3 K 4 -CONH 2 was proposed and the ε-amino groups in lysine residues were acylated by dimethylmaleic amide (DMA), enabling the generated C 16 -A 3 K 4 (DMA)-CONH 2 to self-assemble into negatively charged spherical nanostructure, which relieved the protein adsorption and prolonged blood circulation in vivo. After the access of C 16 -A 3 K 4 (DMA)-CONH 2 into the microbial infection sites, acid-sensitive β-carboxylic amide would hydrolyze to regenerate the positive C 16 -A 3 K 4 -CONH 2 to destabilize the negatively charged bacterial membrane. In the meanwhile, attractively, the self-assembled spherical nanoparticle transformed to rod-like nanostructure, which was in favor of the efficient binding with bacterial membranes due to the larger contact area. Our results showed that the acid-activated AMP nanotherapeutics exhibited strong and broad-spectrum antimicrobial activities against Yeast, Gram-positive Staphylococcus aureus, Gram-negative Escherichia coli, and methicillin-resistant Staphylococcus aureus (MRSA). Moreover, the biocompatible lipopeptide nanotherapeutics dramatically improved the dermapostasis caused by bacterial infection. The strategy of merging pathology-activated therapeutic function and morphological adaptation to augment therapeutic outcomes shows the great potential for bacterial inhibition. STATEMENT OF SIGNIFICANCE: The overall positive charges of antimicrobial peptides (AMPs) lead to undesirable hemolysis and nonselective toxicity, as well as the rapid clearance from blood circulation. Infection-activated lipopeptide nanotherapeutics with adaptable geometrical morphology were developed to address these issues. The self-assembled lipopeptide was pre-decorated to reverse the positive charge to reduce the hemolysis and nonselective cytotoxicity. After accessing the acidic infection sites, the nanotherapeutics recovered the positive charge to destabilize negatively charged bacterial membranes. Meanwhile, the morphology of self-assembled nanotherapeutics transformed from spherical nanoparticles to rod-like nanostructures in the lesion site, facilitating the improved association with bacterial membranes to boost the therapeutic efficiency. These results provide new design rationale for AMPs developed for bacterial inhibition., 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. Published by Elsevier Ltd.)

Background: T cell lymphoma is a complex and highly aggressive clinicopathological entity with a poor outcome. The angioimmunoblastic T-cell lymphoma (AITL) tumor immune microenvironment is poorly investigated., Methods: Here, to the best of our knowledge, spatial transcriptomics was applied for the first time to study AITL., Results: Using this method, we observed that AITL was surrounded by cells bearing immune-suppressive markers. CCL17 and CCL22, the dominant ligands for CCR4, were up-regulated, while the expression of natural killer (NK) cell and CD8+ cytotoxic T lymphocyte (CTL) markers decreased. Colocalization of Treg cells with the CD4+ TFH-GC region was also deduced from the bioinformatic analysis. The results obtained with spatial transcriptomics confirm that AITL has a suppressive immune environment. Chemotherapy based on the CHOP regimen (cyclophosphamide, doxorubicin, vincristine plus prednisone) induced complete remission (CR) in this AITL patient. However, the duration of remission (DoR) remains a concern., Conclusions: This study demonstrates that AITL has an immune suppressive environment and suggests that anti-CCR4 therapy could be a promising treatment for this lethal disease., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s). Published by IMR Press.)

Purpose: Current vaccines for the SARS-CoV-2 virus mainly induce neutralizing antibodies but overlook the T cell responses. This study aims to generate an exosomal vaccine carrying T cell epitope peptides of SARS-CoV-2 for the induction of CD8 + T cell response., Methods: Thirty-one peptides presented by HLA-A0201 molecule were conjugated to the DMPE-PEG-NHS molecules, and mixed with DSPE-PEG to form the peptide-PEG-lipid micelles, then fused with exosomes to generate the exosomal vaccine, followed by purification using size-exclusion chromatography and validation by Western blotting, liquid nuclear magnetic resonance (NMR) test and transmission electron microscopy. Furthermore, the exosomal vaccine was mixed with Poly (I:C) adjuvant and subcutaneously administered for three times into the hybrid mice of HLA-A0201/DR1 transgenic mice with wild-type mice. Then, the epitope-specific T cell responses were detected by ex vivo ELISPOT assay and intracellular cytokine staining., Results: The exosomal vaccine was purified from the Peak 2 fraction of FPLC and injected into the hybrid mice for three times. The IFN-γ spot forming units and the frequencies of IFN-γ + /CD8 + T cells were 10-82-fold and 13-65-fold, respectively, higher in the exosomal vaccine group compared to the Poly (I:C) control group, without visible organ toxicity. In comparison with the peptides cocktail vaccine generated in our recent work, the exosomal vaccine induced significantly stronger T cell response., Conclusion: Exosomal vaccine loading T cell epitope peptides of SARS-CoV-2 virus was initially generated without pre-modification for both peptides and exosomes, and elicited robust CD8 + T cell response in HLA-A transgenic mice., Competing Interests: The authors declare no competing financial interests related to this study., (© 2022 Shen et al.)

Background: Anxiety and depression are common psychological problems in orthodontic patients whose diet habits and oral health status change frequently during treatment. However, relationships between anxiety and depression, digestive tract condition, and impaired oral health-related quality of life remain unknown., Materials and Methods: In this study, clinical assessments, including anxiety, depression, digestive tract condition, and oral health-related quality of life, were collected from 769 outpatients in the orthodontic department using three self-reported questionnaires. Correlation analysis was used to investigate the relationships among different clinical assessments. A chained mediation analysis model was further conducted to explore the direct and indirect effects of these various clinical factors., Results: Changes in digestive tract conditions were positively correlated with the psychological status and oral health-related quality of life. Anxiety and depression partially mediated the relationship between them, and the indirect effect was 0.68 (30%), of which the mediation effect of anxiety accounted for 56%., Conclusion: Anxiety and depression mediate the relationship between gastrointestinal conditions and oral health. In particular, anxiety seems to play a significant mediating role. Our findings indicate that psychological status must be paid more attention to in future clinical practices and supervision for digestive tract symptoms of orthodontic patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tian, Li, Deng, Han, Pu, Han, Du and Deng.)

Objective: Primary Sjogren's syndrome (pSS) is a heterogeneous chronic autoimmune disorder characterized by lymphocyte infiltration of the exocrine glands and the involvement and dysfunction of multiple organs and tissues. Interstitial lung disease (ILD) is the most common type of respiratory system damage. This study ascertained the factors related to ILD in patients with pSS (pSS-ILD), such as altered levels of circulating lymphocyte subtypes., Methods: Eighty healthy controls and 142 patients diagnosed with pSS were included. The pSS patients were classified into groups with pSS-ILD or pSS without ILD (pSS-non-ILD). Baseline clinical and laboratory data were collected for all subjects, including the levels of lymphocytes measured by modified flow cytometry., Results: The pSS-ILD patients were older, had higher ESSDAI scores, had higher positivity rates for anti-SSB and anti-Ro52 antibodies, and had more frequent symptoms of respiratory system involvement than pSS-non-ILD patients. pSS-ILD patients had the lowest Th2 cell counts among the three groups. Although the absolute numbers of Treg and NK cells were lower in pSS patients with and without ILD than in the healthy controls, there was no significant difference between the two pSS groups. The Th1/Th2 ratio was significantly higher in patients with ILD than in patients without ILD. Further analysis showed that older age (OR=1.084), lower Th2 count (OR=0.947), higher Th1/Th2 ratio (OR=1.021), and positivity for anti-SSB (OR=3.620) and anti-Ro52 (OR=5.184) antibodies were associated with the occurrence of ILD in patients with pSS., Conclusion: Decreased circulating Th2 cells and an elevated Th1/Th2 ratio may be the immunological mechanism underlying the development of ILD in pSS patients., (© 2022. The Author(s).)

Objective: To investigate the efficacy and safety of enhanced recovery after surgery (ERAS) in perioperative management of patients with gallbladder carcinoma. Methods: The data of the patients with gallbladder carcinoma admitted at Peking Union Medical College Hospital between January 2017 and December 2021 were analyzed retrospectively. There were 69 males(42.1%) and 95 females(57.9%),with age of (64.0±10.3) years(range:37 to 89 years). Patients were divided into ERAS group( n =53) and normal group( n =111) according to whether they were treated with ERAS measures during the perioperative period.The basic characteristics of the two groups were matched by propensity score matching,and then the perioperative information was compared between the two groups. Categorical variables were presented as absolute numbers or frequencies. Differences between study groups were analyzed using χ 2 test, Fisher's exact test, t -test, or Mann-Whitney U test, as appropriate. Results: Each group had 45 patients after propensity score matching with well-balanced basic characteristics. There was no difference in basic characteristics, operation time,bleeding,complication,and hospitalization expenses between two groups(all P >0.05). Compared with the normal group,time of ambulation ( M (IQR)) (1(1) day vs . 2(2) days; Z =-3.839 ,P <0.01),postoperative anal exhaust time (2(1) days vs . 3(1) days; Z =-3.013 ,P =0.003),feeding time(2(1) days vs . 2(1) days; Z =-3.647 ,P <0.01),postoperative (5(2) days vs . 7(4) days; Z =-3.984 ,P <0.01) and total(8(4) days vs . 13(6) days; Z =-3.605 ,P <0.01) hospitalization time were shorter in ERAS group. Postoperative complications occurred in 12 patients. According to the Clavien-Dindo classification,6,4,and 2 patients were classified as grade Ⅰ,Ⅱ,and Ⅲa,respectively. Conclusion: The ERAS measures is safe and effective for perioperative management of patients with gallbladder carcinoma, enhancing patient recovery and shortening hospitalization time without increasing complication or hospitalization cost.

An efficient approach to access functionalized indole derivatives has been developed through Cu(OTf) 2 -catalyzed C3 aza-Friedel-Crafts alkylation of substituted indoles 5a-5m, N -methyl-pyrrole with linear N , O -acetals 4a-4l. As a result, a series of C3 amide aza-alkylated indole derivatives 6a-6ag and 7 were synthesized in moderate to excellent yields.

Objectives: To assess the effects of periodontitis on renal interstitial fibrosis in a mouse model., Materials and Methods: Thirty C57BL/6 male mice were divided into control, periodontitis (PD), unilateral ureteral ligation (UUO) and PD+UUO groups. Unilateral ureteral ligation was performed 6 days after periodontitis. After 2 weeks, all mice were sacrificed, and samples were collected for the assessment of gene expression, immune cells, biochemical indicators and renal pathology., Results: Expression of tumour necrosis factor-α, interleukin-1β, and Ly6G in the kidneys in the PD+UUO group was significantly greater than in the UUO group. The percentage of CD11b + Ly6G + cells was significantly higher in the PD+UUO than in the UUO group. Fibrotic areas in the kidneys in the PD+UUO group were slightly, but not significantly, greater than those in the UUO group. Kidneys from the PD+UUO group showed markedly higher gene expression of matrix metalloproteinase-9, but not α-smooth muscle actin or collagen I, than those in the UUO group. There were no significant differences in blood urea nitrogen, serum creatinine and uric acid between the PD+UUO and UUO groups., Conclusions: Periodontitis increases the renal inflammatory response without showing a significant influence on renal interstitial fibrosis or renal function in the UUO mouse model., (© 2020 Wiley Periodicals LLC.)

Ethnopharmacological Relevance: Semen Cuscutae, called Tu-si-zi in Chinese, is a kind of dried mature seed in the Convolvulaceae family. It mainly distributes in China, Korea, Pakistan, Vietnam, India and Thailand. It is used as a kidney-tonifying drug for treatment of aging related diseases such as osteoporosis in traditional Chinese medicine. However, the exact mechanisms on bone resorption are poorly studied., Aim of the Study: The aim of this study was to investigate the potential effect of Semen Cuscutae on ovariectomy (OVX)-induced osteoporosis in mice and clarify the exact mechanisms by which Semen Cuscutae exert the anti-osteoporosis effect., Materials and Methods: Qualitative and quantitative analyses of Semen Cuscutae were performed by UPLC-Q-TOF-MS and HPLC-MS/MS, respectively. Changes in bone mineral density (BMD) induced by OVX in mice were measured by dual-energy X-ray absorptiometry and micro-computed tomography (μCT). Tartrate-resistant acid phosphatase (TRAP) staining as well as hematoxylin and eosin (HE) staining were used to observe bone microarchitectural changes. ELISA kits were used to assess the therapeutic effects of Semen Cuscutae on the serum levels of osteoprotegerin (OPG), tartrate-resistant acid phosphatase 5b (TRACP-5b), and receptor activator of nuclear factor-κB (RANKL). The effect of Semen Cuscutae on primary cell viability was assessed using CCK-8 and anti-tartrate phosphatase assays. TRAP staining and actin ring staining were used to observe the effect of Semen Cuscutae on osteoclast differentiation. Western blotting was used to measure the effects of Semen Cuscutae on expressions of NFATC1, c-Src kinase, and c-fos., Results: Results from UPLC-Q-TOF-MS showed that the main components of Semen Cuscutae were flavonoid compounds that included quercitrin, quercetin, hyperoside, caffeic acid, rutin, chlorogenic acid, luteolin, apigenin, kaempferol, isoquercetin, cryptochlorogenic acid, isorhamnetin-3-O-glucoside, and astragalin. After the Semen Cuscutae extract was orally administered to OVX mice, bone density increased (P < 0.01) and bone microstructure was significantly improved (P < 0.01 or 0.05). Additionally, Semen Cuscutae exhibited a significant descending effect in the levels of serum TRACP-5b and RANKL, while there was a significant increase in OPG in the Semen Cuscutae group compared with the OVX group, especially at high doses. Moreover, we found that increasing of c-fos, c-Src kinase, and NFATC1 protein expressions were reversed by Semen Cuscutae in vitro and in vivo., Conclusions: Our results showed that Semen Cuscutae exhibited anti-osteoporosis effects through the c-fos/c-Src kinase/NFATC1 signaling pathway., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Light stimuli have notable advantages over other environmental stimuli, such as more precise spatial and temporal regulation, and the ability to serve as an energy source to power the system. In nature, photoresponsive nanochannels are important components of organisms, with examples including the rhodopsin channels in optic nerve cells and photoresponsive protein channels in the photosynthesis system of plants. Inspired by biological channels, scientists have constructed various photoresponsive, smart solid-state nanochannels membranes for a range of applications. In this review, the methods and applications of photosensitive nanochannels membranes are summarized. The authors believe that this review will inspire researchers to further develop multifunctional artificial nanochannels for applications in the fields of biosensors, stimuli-responsive smart devices, and nanofluidic devices, among others., (© 2021 Wiley-VCH GmbH.)

Following the outbreak of the COVID-19 pandemic, various lockdown strategies restrained global economic growth bringing a significant decline in maritime transportation. However, the previous studies have not adequately recognized the specific impacts of COVID-19 on maritime transportation. In this study, a series of analyses of the Baltic Dry Index (BDI), the China Coastal Bulk Freight Index (CCBFI) and of container throughputs with and without the impact of COVID-19 were carried out to assess changing trends in dry bulk and container transportation. The results show that global dry bulk transportation was largely affected by lockdown policies in the second month during COVID-19, and BDI presented a year-on-year decrease of approximately 35.5% from 2019 to 2020. The CCBFI showed an upward trend in the second month during COVID-19, one month ahead of the BDI. The container throughputs at Shanghai Port, the Ports of Hong Kong, the Ports of Singapore and the Ports of Los Angeles from 2019 to 2020 presented the largest year-on-year drops of approximately 19.6%, 7.1%, 10.6% and 30.9%, respectively. In addition, the authors developed exponential smoothing models of BDI, CCBFI, and container transportation, and calculated the percentage prediction error between the observed and predicted values to examine the impact of exogenous effects on the shipping industry due to the outbreak of COVID-19. The results are consistent with the conclusions obtained from the comparison of BDI, CCBFI, and container transportation during the same period in 2020 and 2019. Finally, on the basis of the findings, smart shipping and special support policies are proposed to reduce the negative impacts of COVID-19., (© 2022 Elsevier Ltd. All rights reserved.)

Objectives: To analyze and summarize the effect of SSA treatment on EAS due to p-NETs (EAS-p-NETs)., Methods: Thirteen patients with EAS-p-NETs treated with SSAs at our center or described in the literature were included in this study. Clinical characteristics, laboratory data, imaging studies, histopathologic results, the effect of SSA treatment, and the prognosis of these EAS-p-NET patients were evaluated., Results: Four males and 9 females with an average age of 42.9 years were included in the study. The mean duration of follow-up was 38.8 ± 28.2 months. As one of the combined treatment measures, SSAs controlled the levels of ACTH and cortisol in 9 of the 13 patients (69.2%). Partial response was observed in 3 patients (23.1%), stable disease in 2 patients (15.4%), and progressive disease in 6 patients (46.2%). The median time to tumor progression was 24 months, and the median overall survival was 61 months. The side effects of SSA treatment included temporary mild abdominal pain, diarrhea, gallstones, and cholecystitis., Conclusions: As a supplemental therapy, SSA treatment led to clinical and biochemical improvement with a good safety profile in patients exhibiting EAS-p-NET with metastasis. However, tumor progression was inhibited by SSA treatment in only a few patients. Combined with other treatments, SSAs may improve the prognosis of patients with EAS-p-NETs., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Da Zhang et al.)

A novel bacterium designated WQ 366  T was isolated from the faeces of Bos taurus, foraging on the slopes of the Baima Snow Mountain in Yunnan, China. The isolate grew optimally at 30 ℃ and pH 7.0-8.0 without NaCl. The cells were Gram-stain-negative, aerobic, rod-shaped, non-gliding, catalase-positive, and produced yellow color colonies on Columbia Agar. A polyphasic study was applied to clarify its taxonomic position through 16S rRNA gene and genome sequence analysis, and other extensive biological typing. Phylogenetic analysis revealed that the isolate was affiliated to the genus Sphingobacterium and its 16S rRNA gene sequence was closely related to Sphingobacterium bovisgrunnientis YK2  T (97.3%), Sphingobacterium composti T5-12  T (96.4%), and Sphingobacterium cavernae 5.0403-2  T (96.4%). The calculated whole genome average nucleotide identity (ANI) and the digital DNA-DNA hybridization values between strain WQ 366  T and the three related strains were 78.3, 78.6, 73.9 and 21.2, 21.2, 21.0%, respectively. The predominant fatty acids (>10%) were iso-C 15:0 , iso-C 17:0 3-OH, Summed Feature 3 (C 16:1 ω7c and/or C 16:1 ω6c), and Summed feature 9 (iso-C 17:1 ω9c and 10-methyl C 16:0 ). The main polar lipids were PE, GPL, GL, and PL. MK-7 was the major menaquinone. The genome size and the G + C content of WQ 366  T was 4.1 Mb and 34.6%, respectively. All these results indicated that strain WQ 366  T represents a novel species of the Sphingobacterium genus. Therefore, the name Sphingobacterium bovistauri sp. nov. is proposed, and the type strain is WQ 366  T (= CCTCC AA 2020029  T  = KCTC 82395  T )., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

A novel Gram-negative strain WQ 585 T , isolated from the faeces of mandrills (Mandrillus sphinx) collected at Yunnan Wild Animal Park, Yunnan province, China, was subjected to a polyphasic taxonomic study. Phylogenetic analysis based on 16S rRNA gene sequences showed that the isolate belongs to the genus Advenella, sharing 98.5% and 98.2% sequence similarity with the type strain Advenella alkanexedens LAM0050 T and Advenella faeciporci M-07 T , respectively. The predominant ubiquinone was Q-8. The major cellular fatty acids (> 10%) were C 16:0, C 17:0  cyclo and Summed Feature 2. The G + C content of the genomic DNA of strain WQ 585 T was 49.0%. The whole genome average nucleotide identity (gANI) values of strain WQ 585 T with strain A. alkanexedens LAM0050 T and A. faeciporci M-07 T were 86.7% and 86.7%, and the digital DNA-DNA hybridization values of strain WQ 585 T with strain A. alkanexedens LAM0050 T and A. faeciporci M-07 T were 64.5% and 62.5%, respectively. Growth occurred at 10-45 °C (optimally at 20-30 °C), pH 6.0-9.0 (optimally at pH 7.0), and 0-5% (w/v) NaCl (optimally at 0.5-2.0%). On the basis of the taxonomic evidence, a novel species, Advenella mandrilli sp. nov., is proposed. The type strain is WQ 585 T (= KCTC 82396  T  = CCTCC AA 2020028  T )., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

In kinship tests, the investigating of the forensic STRs usually provides decisive information to resolve relationship cases. We describe a parentage case with 3 genetic incompatibilities (D6S1043, D18S51 and D2S1338) between the child and alleged parent. With 90 STR loci and 100 SNP loci, the massively parallel sequencing (MPS)-based genotyping results support the certainty of parentage, and the mismatched alleles were considered to be mutations. MPS can provide additional allele sequence structures that can be used to infer the origins of the mutations. SNPs as supplementary markers can provide effective information to give an unequivocal statement of the parentage., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: To investigate the effectiveness of molding custom-made insoles for female patients with foot pain., Methods: The study included 20 patients whose insoles were prescribed according to biomechanical evaluations and molded by repositioning the subtalar joint in its neutral position using a simple set of tools. Plantar biomechanics were measured under the following conditions: static stand, walking at self-comfortable walking speed (CWS) barefoot, walking in patient owned running shoes, and walking in running shoes plus insoles. Each patient's upper arm isometric muscle strength and subjective feelings before and after the insole intervention were assessed., Results: The molded insoles increased plantar contact area both during static standing and walking at CWS compared to the barefoot condition. The insoles also had more evenly distributed plantar contact area and loading rate, with the changes in the medial arch area being most significant. Moreover, the custom-made insole intervention immediately increased maximum resistance and duration of bilateral upper arms, as well as improved foot comfort, especially at the medial arch area during single leg squat tests., Conclusion: Molding custom-made insoles by repositioning the subtalar joint in its neutral position can be accomplished with a simple set of tools, making this method highly applicable for a majority of less developed regions. Insoles molded using this method are effective in immediately improving plantar biomechanics disorders and enhancing isometric upper muscle performance in female patients with foot pain., (© 2021. Huazhong University of Science and Technology.)

Objectives: To compare the levels of serum pepsinogen (PG) in patients with gastric cancer (GC), patients with atrophic gastritis (AG), and healthy donors. Also, we explored the clinical value of PG detection for the diagnosis and treatment of GC., Methods: The PG level in peripheral blood from patients and heathy donors was determined using an Abbott automatic chemiluminescence instrument. The study included 117 patients with GC confirmed by gastroscopy and histopathology, of whom 13 patients had cancer at stage I, 47 at stage II, 41 at stage III, and 16 at stage IV. The AG group included 122 patients, and the control group had 120 healthy donors. The relationship between serum PG levels and the occurrence and development of GC, as well as the evaluation of the clinical value of diagnostic tests based on serum PG detection, were investigated by receiver operating characteristic (ROC) curve analyses., Results: Pepsinogen I (PGI) levels gradually decreased from the control group, the AG group, and the GC group. PGI exhibited high diagnostic value for GC (area under the curve [AUC], 0.834; cutoff, 51.2 ng/mL, sensitivity, 81.7%; specificity, 68.4%), PGII (AUC, 0.587; cutoff value, 13.05 ng/mL; sensitivity, 65.8%; specificity, 53.8%), and PGR (AUC, 0.752; cutoff, 5.65; sensitivity, 54.2%; specificity, 87.2%). The occurrence of GC was negatively correlated with serum levels of PGI (B = -0.054; OR = 0.947; 95% confidence interval [CI], 0.925-0.970; P <.001) and PGR (B = -0.420; OR = 0.657; 95% CI, 0.499-0.864; P = .003)., Conclusions: The combined detection of PGI, PGII, and PGR has important clinical value for the screening, prevention, and diagnosis of GC and could allow for earlier detection, diagnosis, and treatment of GC., (© American Society for Clinical Pathology, 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Cardiovascular safety assessment is vital for drug development, yet human cardiovascular cell models are lacking. In vitro mass-generated human pluripotent stem cell (hPSC)-derived cardiovascular cells are a suitable cell model for preclinical cardiovascular safety evaluations. In this study, we established a preclinical toxicology model using same-origin hPSC-differentiated cardiomyocytes (hPSC-CMs) and endothelial cells (hPSC-ECs). For validation of this cell model, alirocumab, a human antibody against proprotein convertase subtilisin kexin type 9 (PCSK9), was selected as an emerging safe lipid-lowering drug; atorvastatin, a common statin (the most effective type of lipid-lowering drug), was used as a drug with reported side effects at high concentrations, while doxorubicin was chosen as a positive cardiotoxic drug. The cytotoxicity of these drugs was assessed using CCK8, ATP, and lactate dehydrogenase release assays at 24, 48, and 72 h. The influences of these drugs on cardiomyocyte electrophysiology were detected using the patch-clamp technique, while their effects on endothelial function were determined by tube formation and Dil-acetylated low-density lipoprotein (Dil-Ac-LDL) uptake assays. We showed that alirocumab did not affect the cell viability or cardiomyocyte electrophysiology in agreement with the clinical results. Atorvastatin (5-50 μM) dose-dependently decreased cardiovascular cell viability over time, and at a high concentration (50 μM, ~100 times the normal peak serum concentration in clinic), it affected the action potentials of hPSC-CMs and damaged tube formation and Dil-Ac-LDL uptake of hPSC-ECs. The results demonstrate that the established same-origin hPSC-derived cardiovascular cell model can be used to evaluate lipid-lowering drug safety in cardiovascular cells and allow highly accurate preclinical assessment of potential drugs., (© 2021. The Author(s), under exclusive licence to CPS and SIMM.)

Testis is the primary organ of the male reproductive tract in mammals that plays a substantial role in spermatogenesis. Improvement of our knowledge regarding the molecular mechanisms in testicular development and spermatogenesis will be reflected in producing spermatozoa of superior fertility. Evidence showed that N6-Methyladenosine (m6A) plays a dynamic role in post-transcription gene expression regulation and is strongly associated with production traits. However, the role of m6A in bovine testis has not been investigated yet. In this study, we conducted MeRIP-Seq analysis to explore the expression profiles of the m6A and its potential mechanism underlying spermatogenesis in nine bovine testes at three developmental stages (prepuberty, puberty and postpuberty). The experimental animals with triplicate in each stage were chosen based on their semen volume and sperm motility except for the prepuberty bulls and used for testes collection. By applying MeRIP-Seq analysis, a total of 8,774 m6A peaks and 6,206 m6A genes among the studied groups were identified. All the detected peaks were found to be mainly enriched in the coding region and 3'- untranslated regions. The cross-analysis of m6A and mRNA expression exhibited 502 genes with concomitant changes in the mRNA expression and m6A modification. Notably, 30 candidate genes were located in the largest network of protein-protein interactions. Interestingly, four key node genes ( PLK4, PTEN, EGR1 , and PSME4 ) were associated with the regulation of mammal testis development and spermatogenesis. This study is the first to present a map of RNA m6A modification in bovine testes at distinct ages, and provides new insights into m6A topology and related molecular mechanisms underlying bovine spermatogenesis, and establishes a basis for further studies on spermatogenesis in mammals., Competing Interests: T-tY was employed by Henan Dairy Herd Improvement Co., Ltd., Y-yG was employed by Henan Dingyuan Cattle Breeding Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Liu, Ma, Yue, Wang, Qi, Li, Lin, Rushdi, Gao, Fu, Li, Gao, Yang, Han and Deng.)

Three new hydroxyphenylacetic acid derivatives, stachylines E-G (1-3), and a new alkaloid, mortieridinone (4), along with six known compounds (5-10), were isolated from endophytic fungus Mortierella sp. in Epimedium acuminatum Franch. Their structures were determined by their spectroscopic analyses and by comparison with the literature data. Compounds 7 and 10 showed selective antibacterial activity against tested multidrug-resistant bacteria with minimum inhibitory concentration (MIC) values ranging from 25 to 3.13 μg/mL., (© 2021 Wiley-VHCA AG, Zurich, Switzerland.)

Laggera pterodonta, known in China as 'Choulingdan' for its stimulous odor, has long been used as traditional herbal medicine. The essential oil of L. pterodonta, which exhibits various pharmacological activities, is a rich resource of monoterpenes and sesquiterpenes. To date, however, the terpene synthases responsible for their production remain unknown. In present study, a new terpene synthase gene (LpNES1) was identified from L. pterodonta, transcript level of which was significantly upregulated in response to methyl jasmonate treatment. Recombinant LpNES1 could synthesize (E)-nerolidol and minor β-farnesene from farnesyl diphosphate and linalool from geranyl diphosphate in vitro. Whereas, only sesquiterpenes including (E)-nerolidol and minor β-farnesene were released when LpNES1 was reconstituted in yeast, even coexpressed with a geranyl diphosphate synthase (ERG20 WW ). Combined with subcellular localization experiment, the result indicated that the cytosol-targeted LpNES1 was responsible for (E)-nerolidol biosynthesis exclusively in L. pterodonta. Additionally, the expression level of LpNES1 gene was more prominent in floral buds than that in other tissues. LpNES1 characterized in present study not only lays the molecular foundation for sesquiterpene biosynthesis of L. pterodonta, but provides a key element for further biosynthesis of bioactive compound in microbes.

Rice-flavor baijiu is a traditional Chinese liquor. The flavor profile and volatiles presented with or without the solid-state saccharification (SSS) were investigated to reveal the effects of SSS process on the quality of rice-flavor baijiu. The liquor prepared with SSS had a sweet flavor. It contained significantly higher contents of β-phenylethyl alcohol, β-phenylethyl acetate, and ethyl lactate with odor active value of >1. The liquor prepared without SSS had a cheese-like flavor. It was confirmed that the cheese-like flavor derived from butanoic acid was only detected in the liquor prepared without SSS. SSS facilitated the biosynthesis of β-phenylethyl alcohol and ethyl lactate by supplying a large amount of phenylalanine and lactic acid at the initial stage of fermentation, and it prevented contamination. These results indicated that the SSS process contributed to produce the characteristic flavor compounds of rice-flavor baijiu. PRACTICAL APPLICATION: Solid-state saccharification (SSS) process of rice-flavor baijiu contributes not only in brewing, but also in the production of the characteristic flavor compounds and the repression of the off-flavor derived from the contamination. Therefore, SSS is a critical process to control the flavor of rice-flavor baijiu., (© 2021 Institute of Food Technologists®.)

A novel bacterium, WQ 047 T , was isolated from the faeces of Rhinopithecus bieti, a highly endangered primate endemic to China. The cells were aerobic, oval/rod-shaped, Gram-stain-negative, non-motile, catalase positive, and produced yellow pigmented colonies on Columbia Agar. The taxonomic position of WQ 047 T was clarified by applying a polyphasic study based on 16S rRNA gene sequence phylogenetic analysis, extensive biological typing, and whole genome sequencing. Phylogenetic analysis indicated that stain WQ 047 T belonged to the genus Sphingobacterium and its 16S rRNA gene sequence exhibited 96.47% pairwise similarity with that of the closest relatives Sphingobacterium nematocida M-SX103 T . The calculated whole genome average nucleotide identity (ANI) value between strain WQ 047 T and strain M-SX103 was 72.3%. The digital DNA-DNA hybridization value of strain WQ 047 T and M-SX103 T was 15.73%, which was obtained by calculating the genome-to-genome distance. The major fatty acids were C 15:0 iso, C 17:0 iso 3-OH, Summed Feature 3 (C 16:1 ω7c/C 16:1 ω6c) and Summed feature 9 (iso-C 17:1 ω9c and/or 10-methyl C 16:0 ). The predominant polar lipids were PE, PL and APL. MK-7 was the predominant menaquinone. The G + C content of WQ 047 T was 34.89 mol% according to genome analysis. All these characteristics were consistent with those of the genus of Sphingobacterium. Therefore, based on these results, we propose a novel species for which the name Sphingobacterium rhinopitheci sp. Nov. is proposed, with the type strain WQ 047 T (= CCTCC AA 2020026 T  = KCTC82393 T )., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

A novel Gram-stain-negative strain, WQ 117 T , isolated from the faeces of Rhinopithecus bieti collected at Yunnan Snub-nosed Monkey National Park, Yunnan province, PR China, was subjected to a polyphasic taxonomic study. The results of phylogenetic analysis based on 16S rRNA gene sequences indicated that the isolate represented a member of the genus Faecalibacter , sharing 97.64 % sequence similarity with the type strain Faecalibacter macacae YIM 102668 T . The G+C content of the genomic DNA of WQ117 T was 30.5 mol%. The predominant isoprenoid quinone was MK-6. The major cellular fatty acids was iso-C 15 : 0 . The whole genome average nucleotide identity (gANI) values and the digital DNA-DNA hybridization values between WQ 117 T and YIM 102668 T were 79.66 % and 22.20 %, respectively. Growth occurred at 0-50 °C (optimally at 28-35 °C), pH 7.0-9.0 (optimally at pH 8.0) and with 0-2 % (w/v) NaCl (optimally without NaCl). On the basis of the taxonomic evidence, a novel species, Faecalibacter rhinopitheci sp. nov., is proposed. The type strain is WQ 117 T (=KCTC 82394 T =CCTCC AA 2020027 T ).

Malocclusion is one of the three most common oral diseases reported by World Health Organization(WHO). In China, its incidence rate is rising. Malocclusion seriously affects the dental and maxillofacial function, facial appearance and growth development of nearly 260 million children in China, and what is more, it affects their physical and mental health development. Malocclusion occurrence is related to genetic and environmental factors. Early treatment of malocclusion can create a good dental and maxillofacial development environment, correct abnormal growth and control the adverse effects of abnormal genetic factors. It can effectively reduce the prevalence of children's malocclusion and enhance their physical and mental health. This is an urgent need from the economic perspective of our society, so it has great practical and social significance. Experts from the project group "standard diagnose and treatment protocols for early orthodontic intervention of malocclusions of children" which initiated by China National Health Institute of Hospital Administration wrote the "China Experts' Consensus on Preventive and Interceptive Orthodontic Treatments of Malocclusions of Children", which aims to guide and popularize the clinical practice, improve the clinical theory and practice level, and accelerate the disciplinary development of early treatment of children's malocclusion in China. The consensus elaborates the harmfulness of malocclusion and the necessity of early treatment, and brings up the principles and fundamental contents. Based on the law of dental and maxillofacial development, this paper puts forward the guiding suggestions of preventive and interceptive treatments in different stages of dental development ranging from fetus to early permanent dentition. It is a systematic project to promote and standardize the early treatment of malocclusion. Through scientific and comprehensive stratified clinical practice and professional training, the clinical system of early treatment of malocclusion in China will eventually be perfected, so as to comprehensively care for children's dental and maxillofacial health, and improve their oral and physical health in China.

In this work, by combining the superiority of polyoxometalates (POMs) and catalytic single-metal site Co of metalloporphyrin, a series of mixed-valence POM-based metal-organic frameworks (MOFs) composites is synthesized by a post-modification method. The electron-transfer property of POM@PCN-222(Co) composite is significantly enhanced owing to the directional electron-transfer from POM to single-metal site Co in PCN-222(Co). In particular, H-POM@PCN-222(Co) gives a high Faradaic efficiency of 96.2% for electroreduction of CO 2 into CO and good stability over 10 h. DFT calculations confirm that the directional electron transfer, which accelerates the multi-electron transfer from the electrode to active single-metal site Co, enriches the electron density of the Co center, and ultimately reduces the energy of the rate-determining step, thus increasing the catalytic activity of CO 2 reduction reaction (CO 2 RR). This work therefore suggests some new insight for the design of efficient electrocatalysts for CO 2 RR., (© 2021 Wiley-VCH GmbH.)

CTSD/CathD/CATD (cathepsin D) is a lysosomal aspartic protease. A distinguishing characteristic of CTSD is its dual functions of promoting cell proliferation via secreting a pro-enzyme outside the cells as a ligand, and promoting apoptosis via the mature form of this enzyme inside cells; however, the regulation of its secretion, expression, and maturation is undetermined. Using the lepidopteran insect Helicoverpa armigera , a serious agricultural pest, as a model, we revealed the dual functions and regulatory mechanisms of CTSD secretion, expression, and maturation. Glycosylation of asparagine 233 (N233) determined pro-CTSD secretion. The steroid hormone 20-hydroxyecdysone (20E) promoted CTSD expression. Macroautophagy/autophagy triggered CTSD maturation and localization inside midgut cells to activate CASP3 (caspase 3) and promote apoptosis. Pro-CTSD was expressed in the pupal epidermis and was secreted into the hemolymph to promote adult fat body endoreplication/endoreduplication, cell proliferation, and association. Our study revealed that the differential expression and autophagy-mediated maturation of CTSD in tissues determine its roles in apoptosis and cell proliferation, thereby determining the cell fates of tissues during lepidopteran metamorphosis. Abbreviations: 20E: 20-hydroxyecdysone; 3-MA: 3-methyladenine; ACTB/β-actin: actin beta; AKT: protein kinase B; ATG1: autophagy-related 1; ATG4: autophagy-related 4; ATG5: autophagy-related 5; ATG7: autophagy-related 7; ATG14: autophagy-related 14; BSA: bovine serum albumin; CASP3: caspase 3; CQ: choroquine; CTSD: cathepsin D; DAPI: 4',6-diamidino-2-phenylindole; DMSO: dimethyl sulfoxide; DPBS: dulbecco's phosphate-buffered saline; DsRNA: double-stranded RNA; EcR: ecdysone receptor; EcRE: ecdysone response element; EdU: 5-ethynyl-2´-deoxyuridine; G-m-CTSD: glycosylated-mautre-CTSD; G-pro-CTSD: glycosylated-pro-CTSD; HaEpi: Helicoverpa armigera epidermal cell line; HE staining: hematoxylin and eosin staining; IgG: immunoglobin G; IM: imaginal midgut; JH: juvenile hormone; Kr-h1: krueppel homologous protein 1; LM: larval midgut; M6P: mannose-6-phosphate; PBS: phosphate-buffered saline; PCD: programmed cell death; PNGase: peptide-N-glycosidase F; RFP: red fluorescent protein; RNAi: RNA interference; SDS-PAGE: sodium dodecyl sulfate-polyacrylamide gel electrophoresis; SYX17: syntaxin 17; USP1: ultraspiracle isoform 1.