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Chen-Ye Feng *, Shi-Yao Bai *, Meng-Lu Li, Jie-Yu Zhao, Jia-Min Sun, Hui-Jing Bao, Yuan Ren, Xin-Ming Su Department of Pulmonary and Critical Care Medicine, Institute of Respiratory Diseases, The First Affiliated Hospital of China Medical University; Respiratory Disease Institution of China Medical University, Shenyang, Liaoning, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xin-Ming SuDepartment of Pulmonary and Critical Care Medicine, Institute of Respiratory Diseases, The First Affiliated Hospital of China Medical University; Respiratory Disease Institution of China Medical University, 155 North Nanjing Street, Shenyang, 110001, Liaoning, People’s Republic of ChinaEmail xinming_med@126.comBackground: Asthma is a chronic inflammatory disease featured by inflammation and remodeling of airway. Adipose-derived mesenchymal stem cell (ADSCs)-derived exosomal miRNAs have been suggested as promising therapeutic manners for diseases.Methods: ADSCs and airway smooth muscle cells (ASMCs) were isolated from SD rats. Flow cytometry was conducted to detect the surface biomarkers of isolated cells. Exosomes were extracted by sequentially centrifuge method and identified by Western blotting and nanoparticle tracking analysis (NTA). Uptake of exosomes by ASMCs was detected by confocal assay. ASMCs were treated with platelet-derived growth factor-BB (PDGF-BB) to mimic cell remodeling and inflammation. Cell counting 8 (CCK-8), Transwell, and flow cytometry were performed to determine the viability, migration, and apoptosis of ASMCs. Release of inflammatory factors was detected by enzyme-linked immunosorbent assay (ELISA). Levels of RNAs and proteins were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay. Interaction between miR-301a-3p and signal transducer and activator of transcription 3 (STAT3) was determined by luciferase reporter gene assay. The effect of Exosomal miR-301a-3p was analyzed in ovalbumin (OVA)-induced asthma mouse model.Results: ADSCs-derived exosomes could be effectively internalized by ASMCs. Exosomal miR-301a-3p notably suppressed the PDGF-BB-stimulated proliferation and migration of ASMCs, and enhanced apoptosis, as well as decreased the secretion of inflammatory factors. MiR-301a-3p directly targeted the 3ʹUTR region of STAT3. STAT3 overexpression reversed the suppressive effects of exosomal miR-301a-3p on ASMCs under PDGF-BB stimulation. The expression of miR-301a-3p and STAT3 was negative correlation in specimen from patients with asthma. Exosomal miR-301a-3p inhibited OVA-induced lung injury by targeting STAT3 in mice.Conclusion: This study exposed that exosomal miR-301a-3p from ADSCs could effectively alleviate PDGF-BB-stimulated remodeling and inflammation of ASMCs via targeting STAT3, presented ADSCs-derived exosomal miR-301a-3p as a promising therapeutic approach for asthma.Keywords: asthma, mesenchymal stem cell, exosome, miR-301a-3p, STAT3

Objectives: To investigate prevalence, risk factors, and in-hospital outcomes of comatose extracorporeal membrane oxygenation (ECMO) patients., Design: Retrospective observational., Setting: Tertiary academic hospital., Participants: Adults received venoarterial (VA) or venovenous (VV) ECMO support between November 2017 and April 022., Interventions: None., Measurements and Main Results: We defined 24-hour off sedation as no sedative infusion (except dexmedetomidine) or paralytics administration over a continuous 24-hour period while on ECMO. Off-sedation coma (coma off ) was defined as a Glasgow Coma Scale score of ≤8 after achieving 24-hour off sedation. On-sedation coma (coma on ) was defined as a Glasgow Coma Scale score of ≤8 during the entire ECMO course without off sedation for 24 hours. Neurological outcomes were assessed at discharge using the modified Rankin scale (good, 0-3; poor, 4-6). We included 230 patients (VA-ECMO 143, 65% male); 24-hour off sedation was achieved in 32.2% VA-ECMO and 26.4% VV-ECMO patients. Among all patients off sedation for 24 hours (n = 69), 56.5% VA-ECMO and 52.2% VV-ECMO patients experienced coma off . Among those unable to be sedation free for 24 hours (n = 161), 50.5% VA-ECMO and 17.2% VV-ECMO had coma on . Coma off was associated with poor outcomes (p < 0.05) in VA-ECMO and VV-ECMO groups, whereas coma on only impacted the VA-ECMO group outcomes. In a multivariable analysis, requirement of renal replacement therapy was an independent risk factor for coma off after adjusting for ECMO configuration, after adjusting for ECMO configuration, acute brain injury, pre-ECMO partial pressure of oxygen in arterial blood, partial pressure of carbon dioxide in arterial blood, pH, and bicarbonate level (worst value within 24 hours before cannulation)., Conclusions: Coma off was common and associated with poor outcomes at discharge. Requirement of renal replacement therapy was an independent risk factor., 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 © 2024 Elsevier Inc. All rights reserved.)

Ethnopharmacological Relevance: The leaves of Quercus dentata Thunb. (QD), a member of the Fagaceae family and genus Quercus, with distributions in China, Japan, Korea, and other regions. As recorded in the Ben Cao Gang Mu (Compendium of Materia Medica) and other classical Chinese medical texts, QD has been traditionally employed in Traditional Chinese Medicine (TCM) for their hemostatic and diuretic effects and has been used to treat urinary stones (Lin Zheng). It is also the main ingredient of the Mishitong capsule (MST), a Chinese patent drug, used for kidney stones and ureteral stones. Nonetheless, the specific active ingredients and the mechanisms of QD in treating kidney stones remain to be elucidated, which is crucial for advancing the scientific understanding and clinical application of this traditional medicine., Aim of Study: This study aimed to identify the active constituents of QD water extract (QDWE), explore its inhibitory effects on kidney stones through in vitro and in vivo studies, and elucidate the underlying mechanisms of the OPN/CD44 axis and the NLRP3 signaling pathway to provide a full understanding of its potential as a novel treatment approach against kidney stones., Materials and Methods: The micromolecular components in the supernatant of QDWE (QDS) were analyzed by UPLC-Q-Exactive-Orbitrap-MS and the monosaccharide composition of the macromolecular polysaccharide components in the crude polysaccharide (QDP) was determined by pre-column derivatization in HPLC. The effects of QDWE, QDS and QDP on the shape, size, and structure of calcium oxalate (CaOx) crystals in vitro were explored by XRD, FTIR and SEM. The effects of QDWE, QDS and QDP on CaOx kidney stones in SD rats induced by ethylene glycol and VD 3 were compared in vivo. Furthermore, the underlying mechanisms of OPN/CD44 and NLRP3 pathways were investigated by Western blot analysis., Results: There were 32 compounds identified in QDS. The monosaccharide composition ratio of QDP was Man: L-Rha: D-GlcA: D-GalA: D-Glc: D-Gal: L-Ara = 1.01: 22.52: 8.27: 38.61: 3.43: 17.80: 6.38, indicating a mixture of pectin-type acidic heteropolysaccharides. QDP had a more significant inhibitory effect on CaOx crystals in vitro than QDWE, which can inhibit the formation of CaOx monohydrate crystals (COM) and convert them into thermodynamically unstable CaOx dihydrate (COD) crystals. The high dose of QDWE exhibited significant in vivo efficacy (P < 0.05), including anti-calculus, diuretic effects, and kidney protection, marked by decreased calcification and stone formation, alongside improved kidney vitality. Furthermore, the protective effects of QDWE were demonstrated to be associated with the OPN/CD44 and NLRP3 pathways., Conclusion: The studies identified and analyzed the active constituents of QDWE. Among these, QDP significantly inhibited CaOx crystal generation in vitro and could be a potential component for the treatment of urinary stones in QDWE. Moreover, the results indicated that QDWE had a remarkable therapeutic effect on CaOx stones by modulating the OPN/CD44 axis to affect stone formation and the NLRP3 signaling pathway to mediate inflammation, providing an experimental basis for the mechanism of anti-urinary stone and deep development of QD., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

A novel rod-shaped bacterium, designated as strain SYSU D60015 T that formed yellowish colonies was isolated from a sandy soil collected from the Kumtag Desert in Xinjiang, China. Cells were Gram-stain-negative, oxidase-positive, catalase-negative and motile with a single polar flagellum. Growth optimum occurred between 28 and 37 °C, pH 7.0 and with 0-0.5% (W/V) NaCl. The predominant cellular fatty acids (> 5%) were summed feature 8 (C 18:1 ω7c and/or C 18:1 ω6c), C 19:0 cyclo ω8c, C 18:1 ω7c 11-methyl and C 16:0 . The polar lipid profile contained one phosphatidylethanolamine, one diphosphatidylglycerol, one phosphatidylglycerol, one unidentified phospholipid, three unidentified aminolipids, two unidentified aminophospholipids and seven unidentified lipids. The only respiratory quinone was ubiquinone-10. Based on 16S rRNA gene sequence phylogenetic analysis, strain SYSU D60015 T was found to form a distinct linage within the family Sneathiellaceae, and had 16S rRNA gene sequence similarities of 90.8% to Taonella mepensis H1 T , and 90.2% to Ferrovibrio denitrificans S3 T . The genome of SYSU D60015 T was 5.66 Mb in size with 68.2% of DNA G + C content. The low digital DNA-DNA hybridization (dDDH, 18.0%), average nucleotide identity (ANI, 77.5%) and amino acid identity (AAI, 56.0%) values between SYSU D60015 T and Ferrovibrio terrae K5 T indicated that SYSU D60015 T might represent a distinct genus. Based on the phylogenetic, phenotypic, chemotaxonomic and genomic data, we propose Desertibaculum subflavum gen. nov., sp. nov. as a novel species of a new genus within the family Sneathiellaceae. The type strain is SYSU D60015 T (= NBRC 112952 T  = CGMCC 1.16256 T )., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Two Gram-stain-negative, aerobic, milk-white coloured, non-motile, short rod-shaped bacteria, designated as strains SYSU D60010 T and SYSU D60012 T , were isolated from sand samples collected from the Taklimakan Desert of Xinjiang Province in China. Both strains were positive for oxidase, catalase and nitrate reduction, but negative for amylase, H 2 S production, hydrolysis of gelatin and cellulase. Strains SYSU D60010 T and SYSU D60012 T grew well at 28 °C, at pH 7 and had the same NaCl tolerance range of 0-1 % (w/v). The major fatty acids (>5 %) of strains SYSU D60010 T and SYSU D60012 T were summed feature 8 (C 18 : 1  ω 7 c and/or C 18 : 1  ω 6 c ), iso-C 19 : 0 cyclo ω 8 c , C 16 : 0 and iso-C 18 : 1 2-OH. Q-10 was the only respiratory ubiquinone. Strains SYSU D60010 T and SYSU D60012 T showed high 16S rRNA gene sequence similarities to Aestuariivirga litoralis SYSU M10001 T (94.2 and 94.1 %), Rhodoligotrophos jinshengii BUT-3 T (92.0 and 91.9 %) and Rhodoligotrophos appendicifer 120-1 T (91.8 and 91.7 %), and the genomes were 7.4 and 5.8 Mbp in size with DNA G+C contents of 62.8 and 63.0 mol%, respectively. Phylogenetic, phenotypic and chemotaxonomic characteristics indicated that these two strains represent a novel genus and two novel species within the family Aestuariivirgaceae . We propose the name Taklimakanibacter deserti gen. nov., sp. nov. for strain SYSU D60010 T , representing the type strain of this species (=KCTC 52783 T =NBRC 113344 T ) and Taklimakanibacter lacteus gen. nov., sp. nov. for strain SYSU D60012 T , representing the type strain of this species (=KCTC 52785 T =NBRC 113128 T ).

To investigate the effect and safety of percutaneous endovascular angioplasty (PEA) with optional stenting for the treatment of severe stenosis or occlusion of subclavian artery, patients with severe stenosis ≥ 70% or occlusion of subclavian artery treated with PEA were retrospectively enrolled. The clinical data were analyzed. A total of 222 patients were retrospectively enrolled, including 151 males (68.0%) and 71 females (32.0%) aged 48-86 (mean 63.9 ± 9.0) years. Forty-seven (21.2%) patients had comorbidities. Subclavian artery stenosis ≥ 70% was present in 201 (90.5%) patients and complete subclavian occlusion in 21 (9.5%) cases. Angioplasty was successfully performed in all (100%) patients. Balloon-expandable stents were used in 190 (85.6%) cases, and self-expandable stents in 20 (9.0%) cases. Only 12 (5.4%) cases were treated with balloon dilation only. Among 210 patients treated with stent angioplasty, 71 (33.8% or 71/210) cases underwent balloon pre-dilation, 139 (66.2% or 139/210) had direct deployment of balloon-expandable stents, and 2 (1.0% or 2/210) experienced balloon post-dilation. Distal embolization protection devices were used in 5 (2.3% or 5/222) cases. Periprocedural complications occurred in 3 (1.4%) patients, including aortic dissection in 2 (0.9%) cases and right middle cerebral artery embolism in 1 (0.5%). No hemorrhage occurred. Among 182 (82.0%) patients with 6-month follow-up, restenosis > 70% occurred in 1 (0.5%) patient, and among 68 (30.6%) patients with 12-month follow-up, restenosis > 70% took place in 11 (16.2%) patients. Percutaneous endovascular angioplasty can be safely and efficiently performed for the treatment of severe stenosis ≥ 70% or occlusion of subclavian artery., (© 2024. The Author(s).)

This study aims to identify FDA-approved drugs that can target the kappa-opioid receptor (KOR) for the treatment of demyelinating diseases. Demyelinating diseases are characterized by myelin sheath destruction or formation that results in severe neurological dysfunction. Remission of this disease is largely dependent on the differentiation of oligodendrocyte precursor cells (OPCs) into mature oligodendrocytes (OLGs) in demyelinating lesions. KOR is an important regulatory protein and drug target for the treatment of demyelinating diseases. However, no drug targeting KOR has been developed due to the long clinical trials for drug discovery. Here, a structure-based virtual screening was applied to identify drugs targeting KOR among 1843 drugs of FDA-approved drug libraries, and famotidine was screen out by its high affinity cooperation with KOR as well as the clinical safety. We discovered that famotidine directly promoted OPC maturation and remyelination using the complementary in vitro and in vivo models. Administration of famotidine was not only effectively enhanced CNS myelinogenesis, but also promoted remyelination. Mechanically speaking, famotidine promoted myelinogenesis or remyelination through KOR/STAT3 signaling pathway. In general, our study provided evidence of new clinical applicability of famotidine for the treatment of demyelinating diseases for which there is currently no effective therapy., Competing Interests: Declaration of competing interest The authors declare that no conflict of interest exists., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The primary triggers that stimulate the body to generate platelet antibodies via immune mechanisms encompass events such as pregnancy, transplantation, and blood transfusion. Interestingly, our findings revealed that a subset of male patients with hepatocellular carcinoma (HCC), despite having no history of transplantation or blood transfusion, has shown positive results in platelet antibody screenings. This hints at the possibility that certain factors, potentially related to the tumor itself or its treatment, may affect antibody production. To delve the causes we initiated this study. We employed a case-control study approach to analyze potential influential factors leading to the positive results via univariate and multivariate regression analysis. We utilized Kendall's tau-b correlation to examine the relationship between the strength of platelet antibodies and peripheral blood cytopenia. Antitumor medication emerged as an independent risk factor for positive results in HCC patients, and the strength of platelet antibodies positively correlated with the severity of anemia and thrombocytopenia. Without history of blood transfusion, transplantation, pregnancy, those HCC patients underwent recent tumor medication therapy are experiencing peripheral erythrocytopenia or thrombocytopenia, for them platelet antibody screenings holds potential clinical value for prevention and treatment of complications like drug-immune-related anemia and/or bleeding., (© 2024. The Author(s).)

Objective: To analyze the correlative factors of invasion syndrome in patients with diabetes complicated with Klebsiella pneumoniae liver abscess, and to construct and verify the online nomographic prediction model. Methods: A case control study. The clinical data of 213 diabetic patients with Klebsiella pneumoniae liver abscess admitted to the Third Affiliated Hospital of Soochow University from January 1, 2015 to December 31, 2021 were retrospectively analyzed. The patients were divided into the training set (149 cases) and the test set (64 cases) by stratified random sampling method at a ratio of 7∶3. Synthetic minority over-sampling technique(SMOTE) was used to process the imbalanced data, then Lasso regression was used to screen out the optimal feature variables in the training set and multivariate logistic regression model was used to construct the prediction model of invasion syndrome in patients with diabetes complicated with Klebsiella pneumoniae liver abscess, and verify it in the training set and test set. Receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis (DCA) were used to evaluate the prediction efficiency of the model, and the simple and online interactive dynamic web page column graph was constructed. Results: Among the 213 patients, 60 were males and 153 were females, aged of (61.4±12.0) years. A total of 25(11.74%) diabetic patients with Klebsiella pneumoniae liver abscess developed invasion syndrome, which were included in divided into invasive K.pneumoniae liver abscesses syndrome (IKPLAS) group, and the other 188 cases were in without invasive K.pneumoniae liver abscesses syndrome (NIKPLAS) group. SMOTE algorithm was used for oversampling processing, so that the ratio of positive and negative samples was 1∶1. In the oversampling training set, 5 main risk factors were screened based on Lasso regression, namely fasting blood glucose (λ=0.063), hemoglobin (λ=-0.042), blood urea nitrogen (λ=-0.050), abscess size (λ=-0.025) and sequential organ failure assessment (SOFA) score (λ=0.450), respectively. Multivariate logistic regression model showed that fasting blood glucose ( OR =1.20, 95% CI : 0.98-1.48, P =0.006), hemoglobin ( OR =0.90, 95% CI : 0.86-0.95, P <0.001), blood urea nitrogen ( OR =1.22, 95% CI : 1.03-1.43, P =0.017), abscess diameter ( OR =0.76, 95% CI : 0.61-0.94, P =0.010), SOFA score ( OR =3.08, 95% CI : 2.18-4.36, P <0.001) were associated with invasion syndrome in patients with diabetes complicated with Klebsiella pneumoniae liver abscess. The area under the curve of ROC in the training set was 0.966 (95% CI : 0.943-0.989), the sensitivity was 90.5%, and the specificity was 91.3%. The area under the curve of the validation set ROC was 0.946 (95% CI : 0.902-0.991), with a sensitivity of 79.6% and a specificity of 88.9%. The calibration curves drawn in the training set and the test set fit well with the ideal curve. DCA showed that the neomorph prediction model had a good clinical net benefit when predicting the risk of IKPLAS in patients with diabetes complicated with Klebsiella pneumoniae liver abscess was 0.10-0.40. Conclusions: Fasting blood glucose, hemoglobin, urea nitrogen, abscess size and SOFA score are the related factors for invasion syndrome in patients with diabetes complicated with Klebsiella pneumoniae liver abscess. The constructed column graph can effectively predict the risk of invasion syndrome in patients with diabetes complicated with Klebsiae pneumoniae liver abscess.

Aim: To investigate the molecular diagnosis of a three-generation Chinese family affected with aniridia, and further to identify clinically a PAX6 missense mutation in members with atypical aniridia., Methods: Eleven family members with and without atypical aniridia were recruited. All family members underwent comprehensive ophthalmic examinations. A combination of whole exome sequencing (WES) and direct Sanger sequencing were performed to uncover the causative mutation., Results: Among the 11 family members, 8 were clinically diagnosed with congenital aniridia (atypical aniridia phenotype). A rare heterozygous mutation c.622C>T (p.Arg208Trp) in exon 8 of PAX6 was identified in all affected family members but not in the unaffected members or in healthy control subjects., Conclusion: A rare missense mutation in the PAX6 gene is found in members of a three-generation Chinese family with congenital atypical aniridia. This result contributes to an increase in the phenotypic spectrum caused by PAX6 missense heterozygous variants and provides useful information for the clinical diagnosis of atypical aniridia, which may also contribute to genetic counselling and family planning., Competing Interests: Conflicts of Interest: Lin ZB, None; Feng CY, None; Li J, None; Pan AP, None; Sun HS, None; Yu AY, None; Chen SH, None., (International Journal of Ophthalmology Press.)

The asymmetric total synthesis of pedrolide (>200 mg) with an unprecedented [5-5-5-6-6-3] hexacyclic core (pedrolane) was achieved. Its unique bicyclo[2.2.1]heptane ring system was efficiently constructed via an enantioselective ene reaction of cyclopentadiene followed by a Wittig reaction, isomerization, and a diastereoselective intramolecular Diels-Alder reaction cascade. The highly oxygenated carane [6-3] ring system was synthesized via a ring-closing metathesis reaction followed by an unusual free carbene cyclopropanation. Furthermore, the 12 contiguous stereocenters of pedrolide were installed diastereoselectively.

Purpose: This prospective study aimed to investigate estrogen-induced carcinogenesis by assessing the background levels of abasic sites (apurinic/apyrimidinic sites, AP sites) in Taiwanese breast cancer patients following 5 years of postoperative treatment without recurrence (5-year survivors) (n = 70). The study also sought to compare the extent of these DNA lesions with those found in healthy controls and in breast cancer patients prior to treatment., Methods: Abasic sites were measured using an aldehyde reactive probe and quantified as the total number of abasic sites per total nucleotides. Characterization of the abasic sites in subjects recruited for this study was conducted using the abasic site cleavage assay using putrescine or T7 exonuclease (T7 Exo) and/or exonuclease III (Exo III)., Results: The number of abasic sites detected in 5 year survivors (26.7 ± 10.2 per 10 6 total nucleotides, n = 70) was significantly reduced by 46.9% compared to those in breast cancer patients before treatment (50.3 ± 59.2 per 10 6 total nucleotides, P < 0.001), and was similar to the levels observed in healthy controls (23.3 ± 13.5 per 10 6 total nucleotides, P > 0.05). Further investigation into the specific types of abasic sites indicated that the number of abasic sites excisable by putrescine in controls, breast cancer patients, and 5-year survivors were 63.3%, 78.6%, and 67.7%, respectively. These findings suggest the involvement of oxidative stress rather than depurination/depyrimidination of DNA adducts in the formation of abasic sites. Further analyses were performed using exonuclease cleavage assay to characterize the specific types of abasic sites including 5'-cleaved, 3'-cleaved, intact, and residual abasic sites. Results demonstrated that the proportion of residual abasic sites detected in controls, breast cancer patients, and 5-year survivors were estimated to be 32.7%, 48.8%, and 34.0%, respectively., Conclusion: Overall, these findings suggest clear evidence of treatment-related effects on the reduction of levels of abasic sites as well as on the profile of abasic sites in 5 year survivors., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: 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. The authors alone are responsible for the content and writing of this article.

To investigate the seasonal variation, health risks, and potential sources of polycyclic aromatic hydrocarbons(PAHs) in PM 2.5 in the Lüliang area, PM 2.5 samples were collected in Lishi District(downtown area) and Xiaoyi City(suburban area) from October 23, 2018 to July 1, 2019, and the concentrations of 14 PAHs were determined using gas chromatography-mass spectrometry(GC-MS). The annual average concentration of PAHs was 95.50 ng·m -3 , and the concentration of 5-6 ring PAHs was mainly(49.7%), with 3 ring PAHs accounting for a relatively low proportion(8.3%).The concentration of PAHs in Lüliang City showed a seasonal pattern of winter>autumn>spring>summer. The results of the ILCRs model and Monte Carlo simulation showed that the toxicity of PAHs in Lüliang City followed the rule of adults>youth>children. Except in summer, the ILCRs values in the Lishi area were between 10 -6 and 10 -4 , much higher than those in Xiaoyi City, indicating that there was a high potential risk of polycyclic aromatic hydrocarbons in the urban area. Through the characteristic ratio method and positive matrix factorization(PMF), it was shown that the PAHs in Lüliang City were mainly from the combustion of coal and biomass(61.9%) and vehicle exhaust emissions(38.1%). Based on the backward trajectory and potential source factor contribution analysis model, it was determined that the potential sources of PAHs in Lüliang City were mainly distributed in southern Shanxi, northern Shaanxi, and western Inner Mongolia.

Ethnopharmacological Relevance: Astragali Radix (AR) is the dry root of the leguminous plants Astragalus membranaceus (Fisch) Beg. var. mongholicus (Beg) Hsiao, and Astragalus membranaceus (Fisch) Bge., being used as a medicinal and edible resource. AR is used in traditional Chinese medicine prescriptions to treat hyperuricemia, but this particular effect is rarely reported, and the associated mechanism of action is still need to be elucidated., Aim of the Study: To research the uric acid (UA)-lowering activity and mechanism of AR and the representative compounds through the constructed hyperuricemia mouse and cellular models., Materials and Methods: In our study, the chemical profile of AR was analysed by UHPLC-QE-MS, as well as the mechanism of action of AR and the representative compounds on hyperuricemia was studied through the constructed hyperuricemia mouse and cellular models., Results: The main compounds in AR were terpenoids, flavonoids and alkaloids. Mice group treated with the highest AR dosage showed significantly lower (p < 0.0001) serum uric acid (208 ± 9 μmol/L) than the control group (317 ± 11 μmol/L). Furthermore, UA increased in a dose-dependence manner in urine and faeces. Serum creatinine and blood urea nitrogen standards, as well as xanthine oxidase in mice liver, decreased (p < 0.05) in all cases, indicating that AR could relieve acute hyperuricemia. UA reabsorption protein (URAT1 and GLUT9) was down-regulated in AR administration groups, while the secretory protein (ABCG2) was up-regulated, indicating that AR could promote the excretion of UA by regulating UA transporters via PI3K/Akt signalling pathway., Conclusion: This study validated the activity, and revealed the mechanism of AR in reducing UA, which provided experimental and clinical basis for the treatment of hyperuricemia with it., 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.)

Background: Incidence rates of papillary thyroid cancer (PTC) have increased rapidly, with incidentally detected cancers contributing a large proportion. We aimed to explore the impact of incidental detection on thyroid cancer-specific and competing mortality among PTC patients., Methods: We conducted a retrospective cohort study of PTC patients at a cancer center in Guangzhou. Baseline information on detection route and other covariates were collected between 2010 and 2018, and death outcome was followed up for each patient. Cumulative incidence functions were used to estimate the mortality risk of thyroid cancer and competing risk. Cause-specific hazard models were then utilized to explore the association between detection routes and PTC-specific and competing mortality., Results: Of the 2874 patients included, 2011 (70.0%) were detected incidentally, and the proportion increased from 36.9% in 2011 to 82.3% in 2018. During a median follow-up of 5.6 years, 42 deaths occurred, with 60% of them due to competing causes. The probability of competing mortality at 5 years in the non-incidental group and incidental group was 1.4% and 0.4%, respectively, and PTC-specific mortality in the non-incidental group and incidental group was 1.0% and 0.1%, respectively. After adjusting for covariates, the HRs of incidental detection were 0.13 (95% CI: 0.04-0.46; P = 0.01) and 0.47 (95% CI: 0.20-1.10; P = 0.10) on PTC-specific mortality and competing mortality, respectively., Conclusions: Incidental detection is associated with a lower risk of PTC-specific and competing mortality. Under the context of increasing magnitude of overdiagnosis, incorporation of detection route in clinical decision-making might be helpful to identify patients who might benefit from more extensive or conservative therapeutic strategies.

It is imperative to optimally utilize virtues and obviate defects of fully automated analysis and expert knowledge in new paradigms of healthcare. We present a deep learning-based semiautomated workflow (RAINMAN) with 12,809 follow-up scans among 2,172 patients with treated nasopharyngeal carcinoma from three centers (ChiCTR.org.cn, Chi-CTR2200056595). A boost of diagnostic performance and reduced workload was observed in RAINMAN compared with the original manual interpretations (internal vs. external: sensitivity, 2.5% [p = 0.500] vs. 3.2% [p = 0.031]; specificity, 2.9% [p < 0.001] vs. 0.3% [p = 0.302]; workload reduction, 79.3% vs. 76.2%). The workflow also yielded a triaging performance of 83.6%, with increases of 1.5% in sensitivity (p = 1.000) and 0.6%-1.3% (all p < 0.05) in specificity compared to three radiologists in the reader study. The semiautomated workflow shows its unique superiority in reducing radiologist's workload by eliminating negative scans while retaining the diagnostic performance of radiologists., Competing Interests: The authors declare no competing interests., (© 2023.)

A pink-pigmented bacterium, designated as strain SYSU D00476 T , was isolated from sandy soil collected from the Kumtag Desert in China. Colonies were opaque, smooth and of a slight convexity with a clearly defined border. Cells were rod-shaped, Gram-stain-negative, catalase- and oxidase-positive. Growth occurred at 4-45 ℃ (optimum at 28-30 ℃), pH 6.0-8.0 (optimum at 7.0), and with 0-3.0% NaCl (w/v, optimum at 0-2.0%). Major fatty acids (> 10%) were C 16:0 , summed feature 3 (C 16:1 ω7c and/or C 16:1 ω6c), iso-C 17:0 3-OH and iso-C 15:0 . Polar lipids comprised of three unidentified polar aminolipids (ALs), two unidentified aminophosphoglycolipids (APLs), one unidentified glycolipid (GL) and three unidentified phospholipids (PLs). The predominant respiratory quinone was MK-7. The genomic DNA G + C content was 50.5%. The low digital DNA-DNA hybridization (dDDH, 27.4%) and average nucleotide identity (ANI, 85%) values between strain SYSU D00476 T and Telluribacter humicola KCTC 42819 T indicated that SYSU D00476 T represent a distinct species. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain SYSU D00476 T belonged to the genus Telluribacter, showing 97.5% similarity with T. humicola KCTC 42819 T . All these data support that strain SYSU D00476 T represent a novel species of the genus Telluribacter within the family Spirosomataceae, named as Telluribacter roseus sp. nov. The type strain is SYSU D00476 T (= KCTC 82285 T  = CGMCC 1.18647 T  = MCCC 1K04983 T )., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Congenital myasthenic syndromes are rare genetic diseases involving pathologic proteins in the neuromuscular junction. Malignant hyperthermia susceptibility is a genetic disorder involving a hypermetabolic response to volatile anesthetics and depolarizing neuromuscular blocking agents. We present the first reported case of a 3-year-old boy with both congenital myasthenic syndrome and malignant hyperthermia susceptibility, resulting from a mutation in the ryanodine receptor type 1 gene, who underwent an adenotonsillectomy for severe obstructive sleep apnea. We discuss the anesthetic challenges in navigating these 3 comorbidities in the setting of airway surgery., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 International Anesthesia Research Society.)

Background: Thirty-seven patients have received a living-donor kidney transplant in a phase 2 study designed to induce tolerance with facilitated allogeneic hematopoietic stem cell transplant. The study protocol is based on tolerogenic CD8 + /T-cell receptor - facilitating cells (FCR001; also including hematopoietic stem cells and αβ-T-cell receptor + T cells) and low-dose, nonmyeloablative conditioning. Persistent chimerism allowing full immunosuppression (IS) withdrawal was achieved in 26 patients (time off IS 36-123 mo)., Methods: We evaluated biomarkers of tolerance through urinary cell mRNA profiling and immunocompetence to respond to vaccination in these patients. We also assessed kidney function and metabolic parameters compared with standard-of-care patients on IS., Results: Persistently chimeric patients retained chimerism after removal of IS and remained rejection free without donor HLA-specific antibody development. The presence of donor chimerism at >50% correlated with a signature of tolerance in urinary cell mRNA profiles, with a uniquely elevated increase in the ratio of cytotoxic T lymphocyte-associated protein 4 to granzyme B mRNA. Tolerance was associated with protection from recurrence of immune-mediated causes of kidney disease. Tolerant participants were safely vaccinated, developed protective immune responses, and did not lose chimerism after vaccination. When compared with kidney transplant recipients treated with standard IS, tolerant participants showed stable kidney function and reduced medication use for hypertension and hyperlipidemia., Conclusions: These results suggest that elimination of IS has distinct advantages in living-donor kidney allograft recipients., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: This cross-sectional study evaluated the involvement of patients with advanced colorectal cancer (CRC) in treatment decision-making, assessed the treatment efficacy according to their self-reports, and investigated the influencing factors., Methods: Patients with advanced CRC were recruited from 19 hospitals from March 2020 to March 2021 by a multi-stage multi-level sampling method. A self-designed questionnaire was used to collect demographic and clinical characteristics, involvement of CRC patients in treatment decision-making, treatment methods, and self-reported efficacy. Univariate and unordered multinomial logistic regression analyses were used to evaluate the factors affecting the involvement in treatment decision-making and self-reported efficacy., Results: We enrolled 4533 patients with advanced CRC. The average age at diagnosis was 58.7 ± 11.8 years. For the treatment method, 32.4% of patients received surgery combined with chemotherapy, 13.1% of patients underwent surgery combined with chemotherapy and targeted therapy, and 9.7% of patients were treated with surgery alone. For treatment decision-making, 7.0% of patients were solely responsible for decision-making, 47.0% of patients shared treatment decision-making with family members, 19.0% of patients had family members solely responsible for treatment decision-making, and 27.0% of patients had their physicians solely responsible for treatment decision-making. Gender, age, education level, family income, marital status, treatment cost, hospital type, and treatment method were significantly associated with the involvement of patients in treatment decision-making. A total of 3824 patients submitted self-reported efficacy evaluations during treatment. The percentage of patients with good self-reported efficacy was 76.5% (for patients treated for the first time), 61.7% (for patients treated for the second time), and 43.2% (for patients treated after recurrence and metastasis), respectively. Occupation, education level, average annual family income, place of residence, time since cancer diagnosis, hospital type, clinical stage, targeted therapy, and involvement in treatment decision-making were the main influencing factors of self-reported efficacy of treatment., Discussion: Conclusively, CRC patients are not highly dominant in treatment decision-making and more likely to make treatment decisions with their family and doctors. Timely and effective communication between doctors and patients can bolster patient involvement in treatment decision-making., 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 © 2023 Gu, Xu, Liu, Li, Yu, Zhang, Wang, Wang, Du, Duan, Cao, Zhao, Liu, Huang, Cao, Fan, Feng, Lian, Du, Rezhake, Ma and Qiao.)

Objectives: To explore the utilization, barriers, and factors associated with the targeted treatment of Chinese metastatic colorectal cancer (mCRC) patients. Methods: A total of 1,688 mCRC patients from 19 hospitals in 14 cities were enrolled from March 2020 to March 2021 using stratified, multistage cluster sampling. The use of targeted therapy and any barriers patients experienced were collected. Logistic regression analyses were conducted to identify the factors associated with initiating targeted treatment. Results: About 51.6% of the patients initiated targeted therapy, of whom 44.5%, 20.2%, and 35.2% started first-, second-, and third-line treatment, respectively. The most reported barriers were high medical costs and a lack of belief in the efficacy of targeted therapy. Patients treated in the general hospital, diagnosed at an older age, less educated, and who had a lower family income, no medical insurance, poor health-related quality of life, metastasis outside the liver/lung or systemic metastasis, a shorter duration of mCRC were less likely to initiate targeted therapy. Conclusion: Reduced medical costs and interventional education to improve public awareness could facilitate the use of targeted treatment for mCRC., Competing Interests: The authors declare that they do not have any conflicts of interest., (Copyright © 2023 Liu, Zhang, Xu, Shi, Zhao, Du, Liu, Wang, Cao, Ma, Huang, Cao, Li, Fan, Gu, Feng, Zhu, Wang, Du, Zhang, Zhang and Qiao.)

Two Gram-stain-negative strains, designated as SYSU D00286 T and SYSU D00782, were isolated from a sand sample collected from the Kumtag Desert in Xinjiang, north-west China. Cells were aerobic, non-motile and positive for both oxidase and catalase. Growth occurred at 4-37 °C (optimum, 28-30 °C), pH 6.0-7.0 (optimum, pH 7.0) and NaCl concentration of 0-1.5 % (w/v; optimum, 0%). Growth was observed on Reasoner's 2A agar and nutrient agar, but not on Luria-Bertani agar and trypticase soy agar. The polar lipids were identified as diphosphatidylglycerol, phosphatidylcholine, phosphatidylglycerol, three unidentified aminolipids, one unidentified glycolipid and two unidentified phospholipids. The major respiratory quinone was ubiquinone-10 and the major fatty acids (>10 %) were C 16 : 0 and summed feature 8 (C 18 : 1  ω 7 c and/or C 18 : 1  ω 6 c ). The 16S rRNA gene sequence similarity between strains SYSU D00286 T and SYSU D00782 was 100%, and their average nucleotide identity (ANI), average amino acid identity and (AAI) digital DNA-DNA hybridization (dDDH) values were all 100.0 %. Phylogenetic analysis indicated that these two strains belong to the same species of the genus Rubellimicrobium and show the highest sequence similarity to Rubellimicrobium rubrum KCTC 72461 T (98.2 %) and Rubellimicrobium roseum CCTCC AA 208029 T (97.5 %). The ANI, AAI and dDDH values between SYSU D00286 T (as well as SYSU D00782) and the other five Rubellimicrobium type strains were all less than or equal to 83.2, 80.1 and 23.6 %, respectively. Based on their phylogenetic, phenotypic and chemotaxonomical features, strains SYSU D00286 T and SYSU D00782 represent a novel species of the genus Rubellimicrobium , for which the name Rubellimicrobium arenae sp. nov. is proposed. The type strain is SYSU D00286 T (=MCCC 1K04981 T =CGMCC 1.8626 T =KCTC 82271 T ).

Extracorporeal membrane oxygenation (ECMO), in conjunction with its life-saving benefits, carries a significant risk of acute brain injury (ABI). Hypoxic-ischemic brain injury (HIBI) is one of the most common types of ABI in ECMO patients. Various risk factors, such as history of hypertension, high day 1 lactate level, low pH, cannulation technique, large peri-cannulation PaCO 2 drop (∆PaCO 2 ), and early low pulse pressure, have been associated with the development of HIBI in ECMO patients. The pathogenic mechanisms of HIBI in ECMO are complex and multifactorial, attributing to the underlying pathology requiring initiation of ECMO and the risk of HIBI associated with ECMO itself. HIBI is likely to occur in the peri-cannulation or peri-decannulation time secondary to underlying refractory cardiopulmonary failure before or after ECMO. Current therapeutics target pathological mechanisms, cerebral hypoxia and ischemia, by employing targeted temperature management in the case of extracorporeal cardiopulmonary resuscitation (eCPR), and optimizing cerebral O 2 saturations and cerebral perfusion. This review describes the pathophysiology, neuromonitoring, and therapeutic techniques to improve neurological outcomes in ECMO patients in order to prevent and minimize the morbidity of HIBI. Further studies aimed at standardizing the most relevant neuromonitoring techniques, optimizing cerebral perfusion, and minimizing the severity of HIBI once it occurs will improve long-term neurological outcomes in ECMO patients.

Introduction and Methods: We examined the relationship between 24-h pre- and post-cannulation arterial oxygen tension (PaO 2 ) and arterial carbon dioxide tension (PaCO 2 ) and subsequent acute brain injury (ABI) in patients receiving veno-venous extracorporeal membrane oxygenation (VV-ECMO) with granular arterial blood gas (ABG) data and institutional standardized neuromonitoring., Results: Eighty-nine patients underwent VV-ECMO (median age = 50, 63% male). Twenty (22%) patients experienced ABI; intracranial hemorrhage (ICH) was the most common diagnosis (n = 14, 16%). Lower post-cannulation PaO 2 levels were significantly associated with ICH (66 vs. 81 mmHg, p = 0.007) and a post-cannulation PaO 2 level < 70 mmHg was more frequent in these patients (71% vs. 33%, p = 0.007). PaCO 2 parameters were not associated with ABI. By multivariable logistic regression, hypoxemia post-cannulation increased the odds of ICH (OR = 5.06, 95% CI:1.41-18.17; p = 0.01)., Conclusion: In summary, lower oxygen tension in the 24-h post-cannulation was associated with ICH development. The precise roles of peri-cannulation ABG changes deserve further investigation, as they may influence the management of VV-ECMO patients., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Nervonic acid (C24:1 ∆15 , 24:1 ω-9, cis-tetracos-15-enoic acid; NA), a long-chain monounsaturated fatty acid, plays an essential role in prevention of metabolic diseases, and immune regulation, and has anti-inflammatory properties. As a chronic, immune-mediated inflammatory disease, ulcerative colitis (UC) can affect the large intestine. The influences of NA on UC are largely unknown., Purpose: The present study aimed to decipher the anti-UC effect of NA in the mouse colitis model. Specifically, we wanted to explore whether NA can regulate the levels of inflammatory factors in RAW264.7 cells and mouse colitis model., Methods: To address the above issues, the RAW264.7 cell inflammation model was established by lipopolysaccharide (LPS), then the inflammatory factors tumor necrosis factor-α (TNF-α), Interleukin-6 (IL-6), Interleukin-1β (IL-1β), and Interleukin-10 (IL-10) were detected by Enzyme-linked immunosorbent assay (ELISA). The therapeutic effects of NA for UC were evaluated using C57BL/6 mice gavaged dextran sodium sulfate (DSS). Hematoxylin and eosin (H&E) staining, Myeloperoxidase (MPO) kit assay, ELISA, immunofluorescence assay, and LC-MS/MS were used to assess histological changes, MPO levels, inflammatory factors release, expression and distribution of intestinal tight junction (TJ) protein ZO-1, and metabolic pathways, respectively. The levels of proteins involved in the nuclear factor kappa-B (NF-κB) pathway in the UC were investigated by western blotting and RT-qPCR., Results: In vitro experiments verified that NA could reduce inflammatory response and inhibit the activation of key signal pathways associated with inflammation in LPS-induced RAW264.7 cells. Further, results from the mouse colitis model suggested that NA could restore intestinal barrier function and suppress NF-κB signal pathways to ameliorate DSS-induced colitis. In addition, untargeted metabolomics analysis of NA protection against UC found that NA protected mice from colitis by regulating citrate cycle, amino acid metabolism, pyrimidine and purine metabolism., Conclusion: These results suggested that NA could ameliorate the secretion of inflammatory factors, suppress the NF-κB signaling pathway, and protect the integrity of colon tissue, thereby having a novel role in prevention or treatment therapy for UC. This work for the first time indicated that NA might be a potential functional food ingredient for preventing and treating inflammatory bowel disease (IBD)., Competing Interests: Declaration of competing interest The authors declare that there are no financial conflicts of interest in regard to this work., (Copyright © 2023 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Removal of phenolic pollutants from industrial wastewaters is always an important practical problem. Use of enzymes for dephenolization provides a green solution. In this work, enzymatic methods were developed by employing mushroom tyrosinase immobilized as enzyme-Cu 3 (PO 4 ) 2 hybrid nanoflowers and enzyme-metal organic framework (i.e., ZIF-8 and HKUST-1) hybrid composites, which were shown to be superior to processes mediated by tyrosinase immobilized on other supports in both dephenolization efficiency and reusability. Comparatively, tyrosinase@Cu 3 (PO 4 ) 2 and tyrosinase@HKUST-1 were better than tyrosinase@ZIF-8 in both specific activity and dephenolization efficiency. Typical phenolic pollutants, including 3 monophenols (phenol, p-cresol, p-chlorophenol) and 3 bisphenols (BPA, BPB, BPF), can be completely eliminated within 0.5-4 h. The dephenolization order was discussed based on the enzyme's substrate specificity. The operability and reusability of these hybrid biocomposites were highly improved by entrapping into alginate gels or by incorporating with modified magnetic Fe 3 O 4 nanoparticles. Particularly, the magnetic biocatalyst was prepared via a facile one-pot/one-step de novo synthetic strategy, optimized by using response surface methodology (RSM). The as-prepared magnetic tyrosinase@mHKUST-1 retained a high dephenolization efficiency of 81% after 10 cycles and was effective for continuous dephenolization for at least 24 h. These hybrid biocomposites were also successfully applied to treatment of real industrial wastewater from a coke plant., 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 Ltd. All rights reserved.)

Background: As a first-line treatment regimen for Helicobacter pylori ( H. pylori ) infection, antibiotic therapy is widely used worldwide. However, the question of increasing antibiotic resistance must be considered. Given this issue, we need to find ways to reduce drug resistance. This study examined all currently available first-line regimens and compared them with standard triple treatment through a network meta-analysis of randomized controlled trials (RCTs)., Aim: To compare first-line treatment regimens for eradication of antibiotic-resistant H. pylori strains., Methods: To compare the effectiveness of the first-line regimens for treating H. pylori infection, a Bayesian network meta-analysis was applied to process data extracted from RCTs. The plausible ranking for each regimen was assessed by the surface under the cumulative ranking curve (SUCRA). In addition, we conducted a relevant search by reference citation analysis., Results: Twenty-five RCTs involving 12029 participants [including 1602 infected with clarithromycin (CAM)-resistant strains and 1716 infected with metronidazole (MNZ)-resistant strains] were included, in which a total of seven regimens were used for H. pylori eradication. The results showed that dual therapy containing a high-dose proton pump inhibitor (HDDT) [odds ratio (OR): 4.20, 95% confidence interval (CI): 2.29-8.13] was superior to other therapies for all patients, including those with CAM/MNZ-resistant H. pylori infection. In the comparative effectiveness ranking, for CAM-resistant H. pylori , HDDT (OR: 96.80, 95%CI: 22.46-521.9) had the best results, whereas standard triple therapy ranked last (SUCRA: 98.7% vs 0.3%). In the subgroup of high cure rates (≥ 90%), HDDT was also generally better than other therapies., Conclusion: For the eradication of CAM- and MNZ-resistant H. pylori strains, HDDT exhibited considerable advantages. The studies of CAM-resistant H. pylori were based on small samples due to a lack of antibiotic sensitivity tests in many RCTs, but the results showed that all patients, including those with CAM-resistant H. pylori infection, had a concordant trend. Overall, HDDT may be a reference for RCTs and other studies of H. pylori eradication., Competing Interests: Conflict-of-interest statement: All the authors disclose no conflicts of interest for this paper., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Solar greenhouses are important in the vegetable production and widely used for the counter-season production in the world. However, the CO 2 consumed by crops for photosynthesis after sunrise is not supplemented and becomes chronically deficient due to the airtight structure of solar greenhouses. Vegetable crops cannot effectively utilize light resources under low-CO 2 environment, and this incapability results in reduced photosynthetic efficiency and crop yield. We used cucumber as a model plant and generated several sets of transgenic cucumber plants overexpressing individual genes, including β-carbonic anhydrase 1 ( CsβCA1 ), β-carbonic anhydrase 4 ( CsβCA4 ), and sedoheptulose-1,7-bisphosphatase ( CsSBP ); fructose-1,6-bisphosphate aldolase ( CsFBA ), and CsβCA1 co-expressing plants; CsβCA4 , CsSBP , and CsFBA co-expressing plants ( 14SF ). The results showed that the overexpression of CsβCA1 , CsβCA4 , and 14SF exhibited higher photosynthetic and biomass yield in transgenic cucumber plants under low-CO 2 environment. Further enhancements in photosynthesis and biomass yield were observed in 14SF transgenic plants under low-CO 2 environment. The net photosynthesis biomass yield and photosynthetic rate increased by 49% and 79% compared with those of the WT. However, the transgenic cucumbers of overexpressing CsFBA and CsSBP showed insignificant differences in photosynthesis and biomass yield compared with the WT under low-CO 2 .environment. Photosynthesis, fluorescence parameters, and enzymatic measurements indicated that CsβCA1 , CsβCA4 , CsSBP , and CsFBA had cumulative effects in photosynthetic carbon assimilation under low-CO 2 environment. Co-expression of this four genes ( CsβCA1 , CsβCA4 , CsSBP , and CsFBA ) can increase the carboxylation activity of RuBisCO and promote the regeneration of RuBP. As a result, the 14SF transgenic plants showed a higher net photosynthetic rate and biomass yield even under low-CO 2 environment.These findings demonstrate the possibility of cultivating crops with high photosynthetic efficiency by manipulating genes involved in the photosynthetic carbon assimilation metabolic pathway., 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 Chen, Wang, Feng, Guo, Guan, Zhang, Li, Xing, Sun and Tan.)

Long-term non-healing diabetic wounds are always a serious challenge and a global healthcare burden that needs to be resolved urgently in the clinic. Prolonged inflammation and impaired angiogenesis are the main direct causes of diabetic wounds. With the development of polymer biomaterials, various wound dressings have been created, but a few of them have been applied to the clinical management of diabetic wounds. Here, we developed a mussel-inspired bioactive scaffold consisting mainly of collagen and hyaluronic acid, which are natural biopolymer materials contained in human tissues. First, we fabricated different polydopamine modified lyophilized collagen hyaluronic acid scaffolds under different concentrations of dopamine alkaline solutions, 0.5, 1, 2 ​mg/mL, so named CHS-PDA-0.5, CHS-PDA-1, CHS-PDA-2. After testing their physical and chemical properties, antioxidant effect, inflammation regulation, as well as drug loading and release capabilities, we obtained a bioactive endothelial growth factor (EGF)-loaded wound dressing, CHS-PDA-2@EGF, which can resist reactive oxygen species (ROS) and promote the regeneration of chronic wounds in diabetic rats by reducing inflammation. In addition, the scaffold showed excellent swelling ability, a certain coagulation effect and reasonable degradation. Therefore, the scaffold has great potential to be used in clinical diabetic wound treatment as a low-cost and easily available wound dressing to accelerate chronic wound healing., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Wei-Qiang Tan reports administrative support was provided by 10.13039/501100001809National Natural Science Foundation of China. Yong-Zhong Du is a part-time professor of our department from School of Pharmacy, Zhejiang University., (© 2022 The Authors.)

Background: Mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) status serves as a predictor of a poor response to adjuvant chemotherapy among stage 2 colon cancer patients. This study aimed to investigate the efficacy of adjuvant chemotherapy in dMMR/MSI-H gastric cancer (GC)., Methods: Clinical studies comparing adjuvant chemotherapy and surgery alone in dMMR/MSI-H GCs through June 2021 were retrieved to assess the survival of patients managed with both treatments. Two approaches were used to pool the hazard ratio (HR) of survival: (1) if Kaplan-Meier curves and number of patients at risk were provided, individual patient data were extracted. Cox models were used to calculate the HR with its 95% confidence interval (CI); (2) for study-level data, pooled HR was estimated using fixed/random-effects models., Results: Seven clinical studies were assessed. For dMMR/MSI-H versus mismatch repair-proficient (pMMR)/microsatellite stable (MSS)/microsatellite instability-low (MSI-L) status, the estimated 5-year disease-free survival (DFS) rate was 74.2% versus 51.5% (HR, 0.44; 95% CI, 0.32-0.62; P < 0.001) and the estimated 5-year OS rate was 60.5% versus 49.1% (HR, 0.71; 95% CI, 0.60-0.85; P < 0.001). The study-level data showed pooled HRs of 0.42 for DFS (95% CI, 0.31-0.57; P < 0.001) and 0.65 for OS (95% CI, 0.38-1.11; P = 0.114). For adjuvant chemotherapy versus observation of dMMR/MSI-H, the estimated 5-year DFS rate was 76.1% versus 73.3% (HR, 0.72; 95% CI, 0.45-1.15; P = 0.171) and the estimated 5-year OS rate was 73.5% versus 59.7% (HR, 0.62; 95% CI, 0.46-0.83; P = 0.001). Significant survival differences also were observed at study level., Conclusions: The study findings confirm the benefit of adjuvant chemotherapy for dMMR/MSI-H GC patients., (© 2021. Society of Surgical Oncology.)

Background: Colorectal cancer (CRC) poses a significant public health burden worldwide. The investigation of the choice of medical facility among CRC patients is helpful for understanding access to health services and improving quality of oncology services to optimize health outcomes. However, there are limited studies on the topic. The objective of this study was to investigate the choice of medical facility and its associated factors among advanced CRC patients., Methods: This cross-sectional multi-center study included a total of 4,589 individuals with advanced CRC from 19 hospitals in 7 geographic regions in China. Participants were recruited by multi-stage stratified sampling. In the first stage, two cities in each geographic region were selected through simple random sampling. In the second stage, one tertiary cancer hospital and/or one general hospital were selected in each city. Data on medical experience and demographics were collected via a questionnaire during face-to-face interviews. Explanatory variables were selected based on the Andersen behavioral model. Multinomial logistic regression analyses were performed to explore the factors associated with the level of medical facility for the first treatment., Results: Hospitals at the prefecture level were the most common medical facility sought by advanced CRC patients for initial medical care (44.9%), the first definite diagnosis (46.3%), the first treatment (39.5%), and regular follow-up (38.9%). However, the first priority was changed to hospitals at the national level for the second treatment (38.0%) and after recurrence and metastasis (45.9%). Female {odds ratios (ORs) ranged from 1.31 [95% confidence interval (CI): 1.01-1.71] to 1.41 (95% CI: 1.07-1.87)} and relatively well-educated individuals [ORs ranged from 1.74 (95% CI: 1.20-2.53) to 7.26 (95% CI: 4.18-12.60)] preferred to seek higher-level health facilities. Individuals with metastatic CRC at diagnosis were more likely to visit hospitals in provincial capitals versus hospitals at the county level (OR =1.68, 95% CI: 1.27-2.22). Individuals with "good" health-related quality of life (HRQOL) (OR =0.63, 95% CI: 0.49-0.81) were less likely to seek hospitals at the prefecture level compared with hospitals at the county level., Conclusions: There is a need to improve the oncology services for CRC patients, including the optimization of referral reform policy and the promotion of quality of primary healthcare service. The results may provide evidence to fill the policy-implementation gap and potentially contribute to the improvement of the efficiency of the healthcare system., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-1020/coif). All authors report that this research was funded by Merck Serono Co. Ltd. The authors have no other conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Background: Colorectal cancer (CRC) is one of the most common cancers in China, and most CRC patients have already reached an advanced stage by the time of initial diagnosis. Due to the loss of health as a result of cancer, it has consequence on the treatment which may affect the psychophysical and social impairment of CRC patients. These indicators (psychophysical, function and social impairment) affect the health-related quality of life (HRQOL). There are limited studies that focus on advanced CRC patients in China. This study aimed to assess the HRQOL and its associated factors of advanced CRC patients in China., Methods: This was a cross-sectional, nationwide, hospital-based, and multi-center survey. According to the traditional administrative district definition, we selected 19 hospitals in 7 regions by multi-stage stratified sampling in China. For each eligible CRC patient with stage III or IV in the selected hospitals, socio-demographics, clinical information, and HRQOL were collected based on patients' self-reporting and/or medical records between March 2020 and March 2021. Patients completed the Functional Assessment of Cancer Therapy Colorectal (FACT-C) plus-traditional Chinese version of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-9., Results: A total of 4,589 CRC patients (mean age 60.1 years, including 2,730 males and 1,859 females) were included. The total score of HRQOL in population was 128.2±24.70. There were significant differences in the overall score of HRQOL in gender, education level, occupation, region, disease type, and disease stage (P<0.05). The score of HRQOL was better in males, undergraduates and above, unemployed/laid-off, and southwestern and central China. Multivariate analysis showed that education level, occupation, location, number of hospitals visited and treatment methods, and gender were associated with utilities of CRC patients., Conclusions: The HRQOL is an important outcome measure for CRC patients. The HRQOL scores differed according to socio-demographic and clinical characteristics, and findings of these factors were associated with education level, occupation, region, number of visited and treatment methods, and gender., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-991/coif). All authors report this research was funded by Beijing Love Book Cancer Foundation and Merck Serono Co. Ltd. The authors have no other conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Background: Colorectal cancer (CRC) causes a substantial disease burden in China. Information on the medical expenditure of CRC patients is critical for decision-makers to allocate medical resources reasonably, however, relevant data is limited in China, especially advanced CRC. The aim of this survey was to quantify the out-of-pocket medical expenditure of advanced CRC and explore associated factors., Methods: A nation-wide, multi-center, cross-sectional survey was conducted from March 2020 to March 2021. Nineteen hospitals in seven geographical regions were selected by multi-stage stratified sampling. For each eligible CRC patient with stage III or IV disease in the selected hospitals, the socio-demographics, clinical information, and range of out-of-pocket medical expenditure data were collected based on patients' self-reporting or medical records. Multivariable logistic analysis was used to explore associated factors of medical expenditure. All statistical analyses were conducted using SAS 9.4., Results: The mean age of the 4,428 advanced CRC patients included was 59.5±11.6 years, 59.6% were male, and 80.1% of patients were in stage III or IV at the time of diagnosis. Besides, 57.2% of patients had an annual household income of less than 50,000 Chinese Yuan (CNY), 40.9% of patients had an out-of-pocket medical expenditure of 50,000-99,999 CNY. As for the affordability of medical expenditure, 33.2% could afford 50,000-99,999 CNY. Multivariate analysis showed that patients who were in the southern [odds ratio (OR): 1.63, 95% confidence interval (CI): 1.31-2.03] and southwestern (OR: 1.55, 95% CI: 1.25-1.93), were in stage III at the time of diagnosis (OR: 1.33, 95% CI: 1.13-1.57), visited three or more hospitals (OR: 1.26, 95% CI: 1.04-1.52), had sought cross-regional health care (OR: 1.60, 95% CI: 1.40-1.83), used genetic testing (OR: 1.26, 95% CI: 1.10-1.45) and targeted drugs (OR: 2.12, 95% CI: 1.79-2.51) had higher out-of-pocket medical expenditure., Conclusions: Patients with advanced CRC had a high out-of-pocket medical expenditure. It is necessary to strengthen the prevention and control of CRC to reduce the disease burden; also, it is critical to deepen the reform of the medical system, increase proportion of medical insurance reimbursement, and remove barriers to cross-regional health care., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-1001/coif). All authors stated that this research was funded by Merck Serono Co., Ltd. The authors have no other conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Background: The imbalanced allocation of medical resources leads to the occurrence of cross-regional healthcare-seeking in China. Due to the low cure rate, advanced colorectal cancer (CRC) patients may seek cross-regional healthcare for high-level medical facilities. Investigating status of cross-regional healthcare-seeking and its associated factors among advanced CRC patients is important for policymakers to understand access to health services and improve the quality of oncology services., Methods: From March 2020 to March 2021, a cross‑sectional, nation-wide, hospital-based, multi-center survey was conducted. Nineteen hospitals in seven regions were selected by multi-stage stratified sampling. All eligible CRC patients in the selected hospitals were invited to participate in the current study. The outcome variable, cross-regional healthcare-seeking, was defined as seeking health facilities outside the local administration policy of medical insurance. The demographics, clinical information, and medical treatment history of each eligible CRC patient in stage III or IV, were collected through the patients' self-reporting or medical records by trained interviewers. Univariate and multivariate logistic analyses were used to explore the associated factors of cross-regional healthcare-seeking. All statistical analyses were conducted using SAS 9.4., Results: A total of 4,589 individuals with advanced CRC were included. The average age of the patients was 60.1±11.6 years, and 59.5% were males. About 37.5% of the patients suffered from metastatic CRC at first diagnosis. Approximately 36.5% of the patients had sought cross-regional health care previously, and among them, 31.9% had encountered problems. The most common problems included complicated procedures (95.3%), unreimbursed expenses of outpatient service (71.0%), and reimbursement delay (59.4%). Logistic regression analysis showed that patients who completed undergraduate or above [odds ratio (OR) =1.40, 95% confidence interval (CI): 1.13-1.73], had an annual household income of more than 100,000 Chinse Yuan (CNY) (OR =1.46, 95% CI: 1.21-1.78), and had metastasis at diagnosis (OR =1.33, 95% CI: 1.18-1.51) were more likely to seek cross-regional health care., Conclusions: About one third of advanced CRC patients seek cross-regional health care, and 31.9% had encountered problems. There is a need to simplify procedures of reimbursement, optimize direct settlement system and referral mechanisms in order to improve the equality of health services., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-1003/coif). All authors report that the research was funded by Merck Serono Co. Ltd. The authors have no other conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Background: Biomarkers are a key tool in early detection, prognostication, survival, and predicting treatment response of colorectal cancer (CRC). However, little is known about biomarker testing for CRC patients in real-life clinical practice in China. This study aimed to address the usage of biomarker testing and analyze factors related to its acceptance among Chinese patients with advanced CRC., Methods: A multicenter, cross-sectional, hospital-based clinical epidemiology study was conducted from March 2020 to March 2021. Nineteen hospitals were selected in seven geographical regions of China using stratified, multistage, nonrandomized cluster sampling. Data on demographics and clinical characteristics of each eligible CRC patient in stage III or IV diseases were recorded based on the patients' self-reporting and/or medical records. In addition, information on whether biomarker testing [ RAS, BRAF , and microsatellite instability (MSI)] was performed, the results and timing for performing biomarker testing, and the reasons for refusing biomarker testing were also recorded. Univariate and multivariate logistic regression were conducted to explore the potential factors of biomarker testing., Results: A total of 4,526 patients were enrolled in the study, of whom 41.4%, 36.1%, and 28.2% underwent RAS, BRAF , and MSI testing, respectively. RAS, BRAF , and high-level MSI (MSI-high) mutation rates in Chinese patients with advanced CRC were 37.0%, 9.9%, and 8.1%, respectively. The logistic regression analysis revealed that the treating hospital, age at diagnosis, education, family income, tumor site, history of chemotherapy and radiotherapy, and metastases were dependent factors affecting the utilization of biomarker testing in advanced CRC in China (P<0.005)., Conclusions: The biomarker testing rate, especially MSI testing, is less prevalent in clinical practice for patients with advanced CRC in China. Our findings may guide the formulation of biomarker testing of CRC strategies in China and other low-income countries., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-988/coif). All authors report funding from the Beijing Love Book Cancer Foundation and Merck Serono Co., Ltd. The authors have no other conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Background: Colorectal cancer (CRC) is the 3rd most common malignancy globally, and its disease burden is increasing rapidly in China. But CRC patients' knowledge and awareness of CRC have not yet been examined, which could facilitate the identification of targeted population from public for intervention., Methods: A nationwide multicenter cross-sectional survey was conducted in 19 tertiary hospitals (10 cancer hospitals and 9 general hospitals) from March 2020 to March 2021 in China. During study period, all Stage III and IV CRC patients were invited to complete a semi-structured survey that had been designed to collect information about their socio-demographic characteristics, and knowledge and awareness of CRC risk factors and screening. A multivariate logistic regression model was used to identify factors associated with their knowledge and awareness., Results: In total, 4,589 advanced CRC patients were enrolled in this study, of whom, 46.2% were from tertiary cancer hospitals, and 59.5% were male. Patients had a mean age of 60.1±11.6 years. Before diagnosis, 65.1% of the patients had no related knowledge of the CRC risk factors, and 84.9% were unaware of the CRC screening-related information. Only 30.4% of patients had actively sought to acquire CRC-related knowledge before diagnosis. The 3 most common knowledge sources were relatives or friends who had been diagnosed with CRC (13.2%), popular science television/broadcast shows (12.9%), and community publicity and education (9.6%). Generally, knowledge and awareness were positively associated with better education level [odds ratios (ORs) ranged from 1.49 to 2.54, P<0.001], annual household income ranged from 50,000 Chinese Yuan (CNY) to 100,000 CNY (OR =1.32, P<0.001), being manual laborer (OR =1.25, P<0.001) and being white-collar worker (OR =1.47, P<0.001)., Conclusions: Advanced CRC patients' knowledge and awareness of CRC were severely limited before diagnosis. Thus, those who had limited knowledge and awareness should has a priority for intervention., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-1019/coif). All authors report that this research was funded by Merck Serono Co., Ltd. The authors have no other conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Objectives: Autologous reconstruction of microtia is advantageous due to its inherent biocompatibility and long-term stability, but postoperative pain associated with costal harvest is a significant issue. A well-planned pain management approach is imperative. Our objective is to introduce the novel application of erector spinae block anesthesia in pediatric microtia reconstruction and evaluate its impact on pain scores, use of opioids, and hospital length of stay., Study Design: Case series with chart review., Setting: Patients undergoing stage 1 microtia reconstruction at a tertiary pediatric hospital., Methods: Data collected included demographics, opioid amounts, Wong-Baker FACES Pain Rating Scale scores, opioid-related side effects, and hospital length of stay. We used generalized estimating equations to examine the effect of erector spinae block use on total opioid use and pain scores and a linear regression model to assess the effect on hospital stay., Results: Forty-seven patients were included: 14 in the erector spinae block group and 33 in the continuous wound pump group. The mean age was 8.3 years (SD, 2; range, 6-13), and 13 (32%) were female. Patients in the erector spinae block group had a 65.44% decrease in adjusted total opioid use (95% CI, -79.72% to -41.10%; P < .0001), a decrease in length of hospital stay (β = -1.69 [95% CI, -2.11 to -1.26], P < .0001), and no difference in reported pain scores when compared with patients in the continuous wound pump group., Conclusions: This study demonstrates that early experience with an erector spinae block resulted in decreased opioid use and shorter hospital stay as compared with continuous wound infiltration with local anesthetic.

The epidural blood patch is the gold-standard therapy to treat postdural puncture headaches from dural puncture when conservative therapies fail. However, an epidural blood patch is contraindicated in patients with coagulopathy and thrombocytopenia (platelet count of 60,000/µL) due to concerns of an epidural hematoma. We present a case of an adolescent with acute lymphocytic leukemia, thrombocytopenia, and persistent postdural puncture headaches. The patient was successfully treated with a sphenopalatine ganglion nerve block at the bedside without any side effects and complications., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Aims: The aim of this study was to simultaneously analyze estrogen quinone-derived adducts, including 17β-estradiol-2,3-quinone (E 2 -2,3-Q) and 17β-estradiol-3,4-quinone (E 2 -3,4-Q), in human albumin (Alb) and hemoglobin (Hb) derived from breast cancer patients with five-year postoperative treatment without recurrence in Taiwan and to evaluate the treatment-related effects on the production of these adducts., Settings and Design: Cohort Methods and Material: Blood samples derived from breast cancer 5-year survivors without recurrence were collected. Albumin and hemoglobin adducts of E 2 -3,4-Q and E 2 -2,3-Q were analyzed to evaluate the degree of disposition of estrogen to quinones and to compare these adduct levels with those in patients before treatment., Statistical Analysis: All data are expressed as mean ± standard deviation of three determinations. We used Student's t -test to examine subgroups. Data were transformed to the natural logarithm and tested for normal distribution for parametric analyses. Linear correlations were investigated between individual adduct levels by simple regression. Statistical analysis was performed using the SPSS Statistics 20.0., Results: Result confirmed that logged levels of E 2 -2,3-Q-derived adducts correlated significantly with those of E 2 -3,4-Q-derived adducts (correlation coefficient r =.336-.624). Mean levels of E 2 -2,3-Q-4-S-Alb and E 2 -3,4-Q-2-S-Alb in 5-year survivors were reduced by 60-70% when compared to those in the breast cancer patients with less than one year of diagnosis/preoperative treatment (P<.001)., Conclusions: Our findings add support to the theme that hormonal therapy including aromatase inhibitors and Tamoxifen may dramatically reduce burden of estrogen quinones. We hypothesize that combination of treatment-related effects and environmental factors may modulate estrogen homeostasis and diminish the production of estrogen quinones in breast cancer patients.

Although metal-organic frameworks (MOFs) have been considered as promising matrices for enzyme immobilization, HKUST-1, constructed from copper acetate (CuAc 2 ) and benzene 1,3,5-tricarboxylate (BTC), has rarely been explored for this application. In this study, mushroom tyrosinase (EC 1.14.18.1) was immobilized in the form of tyrosinase@HKUST-1 following a simple reaction procedure by mixing BTC with the enzyme prior to addition of CuAc 2 . The resultant biocatalyst was characterized in both structural features and catalytic properties. Upon incorporation into the HKUST-1 frameworks, the enzyme gained a prominent enhancement in stability against pH, temperature and storage: When incubated at 50 °C and pH 6.0, tyrosinase@HKUST-1 presented a half-life of 32.6 h, which is 77-fold and over tenfold higher than that of the free enzyme and its other immobilization forms, respectively; and the catalyst fully maintained its activity for at least 2 months when stored at 30 °C. The applicability of this new biocatalyst was demonstrated by employing it as catalyst for regioselective ortho-hydroxylation reactions to produce catecholic products with huge pharmacological effects, i.e., hydroxytyrosol and L-DOPA, with excellent yields and productivities. This study has thus offered a facile immobilization method to prepare a novel biocatalyst with super stability, and tyrosinase@HKUST-1 so formed from crude mushroom extract provides an efficient catalyst which can be applied to the production of catecholic products with health benefits., (© 2021. The Author(s).)

Three eastern bongos (Tragelaphus eurycerus isaaci) presented acutely with hemorrhagic diarrhea at the Singapore Zoo, thought to be caused by a mouldy batch of hay. Repeated fecal tests were negative of parasites and common gastrointestinal bacteria including salmonella and campylobacter. The diarrhea resolved for all individuals after a week of leaf-only diet. However, 2 individuals developed signs of colic. Both animals were anesthetized for examination including blood tests and imaging studies. The findings were consistent of gastrointestinal ileus and a possible impaction. With intensive treatment involving repeated sedations for fluid therapy administration and treatments for gastrointestinal impaction, one individual eventually made a full recovery, but the other individual died due to septic peritonitis secondary to a rupture in the spiral colon. Persistent supportive therapy may be vital in treating severe gastrointestinal disease in this species.

Abstract: To investigate the clinicopathological features and outcomes of primary IgA nephropathy with nephrotic-range proteinuria in Chinese children. Patients with biopsy-proven IgA nephropathy and nephrotic-range proteinuria between January 2011 and December 2017 were included, and their proteinuria and renal function were followed up. A total of 90 patients were enrolled, and 21.1% (19/90) of them had decreased renal function at diagnosis. Complete remission, partial remission, and no response of proteinuria occurred in 88.6% (70/79), 10.1% (8/79), and 1.3% (1/79), respectively, of the 79 patients who were followed up for 6 to 104 months. 73.7% (14/19) of the patients with decreased renal function at diagnosis recovered to normal level while 26.3% (5/19) of them did not recover or progressed to end-stage renal disease. Two patients with normal renal function at diagnosis progressed to renal insufficiency during follow-up period. By multivariate analysis, the risk for renal function deterioration was significantly higher in the partial remission and no response groups than in the complete remission group. Remission of proteinuria was important for improving renal prognosis in children with IgA nephropathy and nephrotic-range proteinuria. The outcomes for pediatric patients appeared to be better than that reported in adults., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

The Sunda pangolin (Manis javanica) is one of the most trafficked animal species globally, and is listed as Critically Endangered by the IUCN. There is limited information on reproductive biology or pathology of this species. We now document the clinical and pathological features of pyelonephritis and cystic endometrial hyperplasia in one of these animals. Ultrasonographic examination revealed pathological changes in the kidneys and uterus. On histopathological examination, there was marked interstitial infiltration of macrophages, neutrophils and lymphocytes in kidney tissue, fibrinonecrotic ureteritis and mild endometrial hyperplasia. This first report of these urogenital lesions in this species will be valuable for the conduct of health and reproductive assessments of the Sunda pangolin, which inform conservation and ex-situ management of this species., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Lotus plumule, the embryo of the seed of the sacred lotus (Nelumbo nucifera), contains a high accumulation of secondary metabolites including flavonoids and possesses important pharmaceutical value. Flavonoid C-glycosides, which accumulate exclusively in lotus plumule, have attracted considerable attention in recent decades due to their unique chemical structure and special bioactivities. As well as mono-C-glycosides, lotus plumule also accumulates various kinds of di-C-glycosides by mechanisms which are as yet unclear. In this study we identified two C-glycosyltransferase (CGT) genes by mining sacred lotus genome data and provide in vitro and in planta evidence that these two enzymes (NnCGT1 and NnCGT2, also designated as UGT708N1 and UGT708N2, respectively) exhibit CGT activity. Recombinant UGT708N1 and UGT708N2 can C-glycosylate 2-hydroxyflavanones and 2-hydroxynaringenin C-glucoside, forming flavone mono-C-glycosides and di-C-glycosides, respectively, after dehydration. In addition, the above reactions were successfully catalysed by cell-free extracts from tobacco leaves transiently expressing NnCGT1 or NnCGT2. Finally, enzyme assays using cell-free extracts of lotus plumule suggested that flavone di-C-glycosides (vicenin-1, vicenin-3, schaftoside and isoschaftoside) are biosynthesized through sequentially C-glucosylating and C-arabinosylating/C-xylosylating 2-hydroxynaringenin. Taken together, our results provide novel insights into the biosynthesis of flavonoid di-C-glycosides by proposing a new biosynthetic pathway for flavone C-glycosides in N. nucifera and identifying a novel uridine diphosphate-glycosyltransferase (UGT708N2) that specifically catalyses the second glycsosylation, C-arabinosylating and C-xylosylating 2-hydroxynaringenin C-glucoside., (© 2021 Society for Experimental Biology and John Wiley & Sons Ltd.)