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Hot springs are extreme ecological environments of microbes. The study is the first comparative analysis of bacterial diversity of Tangchi and Bantang hot spring water samples collected in Hefei, China, which is conducive to the further development and utilization of microbial resources in hot springs. Illumina MiSeq system was utilized to sequence and analyze the bacterial 16S rRNA gene from hot spring water samples by bioinformatics, to probe into the bacterial abundance and diversity of two hot springs in Hefei. Results revealed that prevalent bacterial phyla in Tangchi hot spring were Bacillota and Aquificota, and the prevalent bacterial genus was Hydrogenobacter; prevalent phyla in Bantang hot spring were Pseudomonadota followed by Actinobacteriota, and prevalent genera were CL500-29_marine_group and Polynucleobacter. More species and higher evenness in Bantang hot spring than those in Tangchi hot spring. In MetaCyc pathway analysis, the major pathways of metabolism existed in the bacteria from the two hot springs were 'pyruvate fermentation to isobutanol (engineered)', 'acetylene degradation', 'carbon fixation pathways in prokaryotes', 'nitrate reduction I (denitrification)', 'methanogenesis from acetate', 'superpathway of glucose and xylose degradation', etc., (© 2023. The Author(s).)

This study examined the effectiveness of a DNA vaccine for S. agalactiae that was delivered by mannose-based polyethyleneimine (Man-PEI). The results showed that Man-PEI/pcDNA-Sip stimulated a higher serum antibody titer compared to control or other vaccine groups (p < 0.05). Additionally, it induced higher expression of immune-related genes, and increased activities of superoxide dismutase (SOD), acid phosphatase (ACP) and alkaline phosphatase (AKP). Furthermore, the Man-PEI/pcDNA-Sip group showed an improved relative percent survival (RPS) of 85.71%. These results demonstrate the potential value of Man-PEI as a vaccine delivery vehicle, and suggest that it can be effective in boosting the immune protective rate induced by pcDNA-Sip vaccines., Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work; there is no professional or other personal interest of any nature or kind in any product, service, or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: To explore the application value of cervical exfoliated cell DNA methylation (CDO1 m and CELF4 m ) combined with or without transvaginal sonography (TVS) for screening endometrial cancer in postmenopausal women. Methods: A total of 143 postmenopausal women who underwent hysteroscopy for suspected endometrial lesions in the Department of Obstetrics and Gynecology of Peking Union Medical College Hospital from May 2020 to October 2021 were enrolled in this study. The cervical exfoliated cells were collected for gene methylation before hysteroscopy. Clinical information, tumor biomarkers, and endometrial thickness of TVS were also collected. With endometrial histopathology as the gold standard, multivariate unconditional logistic regression was applied to analyze the risk factors of endometrial cancer. The role of gene methylation with or without TVS were specifically explored. Results: The 143 patients were divided into an endometrial cancer group ( n =56) and a control group ( n =87), aged (59.27±6.45) and (61.07±8.26) years, respectively ( P =0.051). Multivariate logistic regression analysis showed that, CA125≥35 U/ml, postmenopausal bleeding, endometrial thickness≥5 mm, CDO1 m ΔCt≤8.4, and CELF4 m ΔCt≤8.8 were the risk factors for endometrial cancer, with OR (95% CI ) of 33.23 (2.51-1 335.28), 8.41(1.81-39.05), 14.45 (2.35-88.84), 17.34 (3.34-89.98), and 44.01 (6.79-285.25), respectively (all P values < 0.05). The sensitivity and specificity of dual-gene methylation (CDO1 or CELF4) in the screening of endometrial carcinoma were both higher than others factors, reaching 87.5% (95% CI : 75.9%-94.8%) and 90.8% (95% CI : 82.7%-95.9%), respectively. TVS combined with DNA methylation detection further improved the sensitivity to 100.0% (95% CI : 93.6%-100.0%), but could not improve the specificity (59.8%, 95% CI : 48.8%-70.1%). Conclusions: In postmenopausal women with suspected endometrial lesions, the accuracy of cervical cytology DNA methylation is better than other noninvasive clinical indicators for the screening of endometrial cancer. DNA methylation combined with TVS can further improve the sensitivity of screening.

We report the complete mitochondrial genome of Rhinogobius lentiginis , which was found to be a circular molecule of 16,633 bp in length and included 13 protein-coding genes (PCGs), 2 rRNA genes, 22 tRNA genes, and a non-coding control region. The overall base composition was 28.44% A, 26.21% T, 16.33% G, and 29.02% C. Phylogenetic analyses using maximum-likelihood and Bayesian inference methods revealed a close genome relationship among R. lentiginis , R. niger , R. shennongensis and R. maculagenys . The complete mitogenome of R. lentiginis will provide a valuable resource for species classification and conservation., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Objectives: To investigate the clinical features of juvenile myelomonocytic leukemia (JMML) and their association with prognosis., Methods: Clinical and prognosis data were collected from the children with JMML who were admitted from January 2008 to December 2016, and the influencing factors for prognosis were analyzed., Results: A total of 63 children with JMML were included, with a median age of onset of 25 months and a male/female ratio of 3.2∶1. JMML genetic testing was performed for 54 children, and PTPN11 mutation was the most common mutation and was observed in 23 children (43%), among whom 19 had PTPN11 mutation alone and 4 had compound PTPN11 mutation, followed by NRAS mutation observed in 14 children (26%), among whom 12 had NRAS mutation alone and 2 had compound NRAS mutation. The 5-year overall survival (OS) rate was only 22%±10% in these children with JMML. Of the 63 children, 13 (21%) underwent hematopoietic stem cell transplantation (HSCT). The HSCT group had a significantly higher 5-year OS rate than the non-HSCT group (46%±14% vs 29%±7%, P <0.05). There was no significant difference in the 5-year OS rate between the children without PTPN11 gene mutation and those with PTPN11 gene mutation (30%±14% vs 27%±10%, P >0.05). The Cox proportional-hazards regression model analysis showed that platelet count <40×10 9 /L at diagnosis was an influencing factor for 5-year OS rate in children with JMML ( P <0.05)., Conclusions: The PTPN11 gene was the most common mutant gene in JMML. Platelet count at diagnosis is associated with the prognosis in children with JMML. HSCT can improve the prognosis of children with JMML.

The first complete mitochondrial genome of the freshwater goby Rhinogobius davidi was determined by high-throughput sequencing. This genome was 16,627 bp in length and consisted of 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes, and 2 non-coding control regions. Phylogenetic analysis based on the amino acid sequences of 13 mitochondrial protein-coding genes from R. davidi and 23 relatives suggested that R. davidi had a close mitogenome relationship with Rhinogobius giurinus . This complete genome of R. davidi will provide basal molecular data for future studies on taxonomy, comparative genomics, and adaptive evolution in Rhinogobius ., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Antibiotic contaminants can migrate over long distances in the water, thus possibly causing severe detriment to the environment and even potential harm to human health. Heterogeneous activation of peroxymonosulfate (PMS) assisted by visible light is an emerging and promising technology for the purification of such wastewater. This study designed an ultra-efficient and stable PMS activator (FeCN) to restore the typical antibiotic-polluted water under harsh conditions. About 90.94% of sulfamethoxazole (SMX) was degraded in 35 min in the constructed FeCN+PMS/vis system, and the reaction rate constant was nearly 50-fold higher than direct photocatalysis. Electron spin resonance, quenching experiments, LC/MS technique, eco-toxicity assessment, and density functional theory validated that the SMX removal was dominated by the attack of h + , • O 2 - and 1 O 2 on the active atoms of SMX molecules with high Fukui index, presenting as a simultaneous degradation and detoxification process. Such a visible-light-assisted PMS activation system also had good resistance to the environmental water bodies and a broad spectrum in the degradation of various pollutants. In particular, Cl - (50 mM) could significantly accelerate the removal of SMX with a 32.6-fold increase in catalytic activity, and the mineralization efficiency could reach 56.6% under identical conditions. Moreover, this Cl - containing system excluded the degradation products of disinfection by-products, and such a system was also versatile for different contaminants. This work demonstrates the feasibility of the FeCN+PMS/vis system for the remediation of antibiotic-contaminated wastewater in the presence and absence of Cl - , and also highlights their great potential in WWTPs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

It has been considered challenging to develop ideal adsorbents for efficient and lower adsorption time uranium extraction, especially 3D covalent organic frameworks with interpenetrating topologies and tunable porous structures. Here, a "soft" three-dimensional (3D) covalent organic framework (TAM-DHBD) with a fivefold interpenetrating structure is prepared as a novel porous platform for the efficient extraction of radioactive uranium. The resultant TAM-DHBD appears exceptional crystallinity, prominent porosity and excellent chemical stability. Based on the strong mutual coordination between phenolic-hydroxyl/imine-N on the main chain and uranium, TAM-DHBD can effectively avert the competition of other ions, showing high selectivity for uranium extraction. Impressively, the 3D ultra-hydrophilic transport channels and multi-directional uniform pore structure of TAM-DHBD lay the foundation for the ultra-high-speed diffusion of uranium (the adsorption equilibrium can be reached within 60 min under a high-concentration environment). Furthermore, the utilization of lightweight structure not only increases the adsorption site density, but renders the adsorption process flexible, achieving a breakthrough adsorption capacity of 1263.8 mg g -1 . This work not only highlights new opportunities for designing microporous 3D COFs, but paves the way for the practical application of 3D COFs for uranium adsorption., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: This study was conducted to investigate key long noncoding RNAs (lncRNAs) involved in competitive endogenous RNA (ceRNA) network associated with laryngeal squamous cell carcinoma (LSCC)., Materials and Methods: Three mRNA datasets, two miRNA datasets, and one lncRNA dataset of LSCC were downloaded from GEO database. Following the identification of differentially expressed mRNAs (DEmRNAs), (microRNAs) miRNAs (DEmiRNAs), and lncRNAs (DElncRNAs) in LSCC compared with adjacent tissues, functional enrichment of DEmRNAs was performed. Then, construction of the ceRNA (DElncRNA-DEmiRNA-DEmRNA) regulatory network and functional analyses of all DEmRNAs in ceRNA regulatory network were conducted. Quantitative real-time polymerase chain reactions (qRT-PCR) were used to detect the expression levels of selected DEmRNAs, DEmiRNAs, and DElncRNAs., Results: A total of 3449 DEmRNAs, 40 DEmiRNAs, and 100 DElncRNAs were identified in LSCC. The ceRNA networks, which contained 132 DElncRNA-DEmiRNA pairs and 287 DEmiRNA-DEmRNA pairs, involving 44 lncRNAs, 3 miRNAs, and 271 mRNAs, were obtained. DEmRNAs in ceRNA regulatory networks were significantly enriched in pathways in cancer, prostate cancer, and aldosterone-regulated sodium reabsorption. Except for HCG22 and hsa-miR-1246, expressions of the others in the qRT-PCR results played the same pattern with that in our integrated analysis, generally., Conclusions: We concluded that HCG22/EGOT-hsa-miR-1275-FAM107A and HCG22/EGOT-hsa-miR-1246-Glycerol-3-phosphate dehydrogenase 1 like interaction pairs may play a central role in LSCC., (© 2021 Wiley Periodicals LLC.)

Ethnopharmacological Relevance: Polygoni Multiflori Radix Praeparata (Zhiheshouwu) has been a Wudang Taoist medicine for tonifying the liver and kidney, resolving turbidity and reducing lipid. Emodin is one of the active anthraquinones in Zhiheshouwu. Our previous studies showed that emodin (EM) and the other anthraquinones in Zhiheshouwu extract (HSWE) exerted similar inhibitory effects on liver cancer cells in vitro. However, it is still unknown if the other anthraquinones enhance pharmacokinetics (PK) of EM in HSWE in vivo., Aim of the Study: In this study, we compared the PK characteristics of EM alone with that in Zhiheshouwu aiming to explore which anthraquinones in HSWE contribute to the changed PK of EM in rats., Materials and Methods: Quality control of HSWE was determined using high performance liquid chromatography (HPLC). The ratios of emodin to other anthraquinones, physcion (PH), chrysophanol (CH), rhein (RH), aloe-emodin (AE), emodin-8-O-β-D-glycoside (EMG), physcion-1-O-β-D-glycoside (PHG) and chrysophanol-8-O-β-D-glycoside (CHG) in HSWE were determined and analyzed using UPLC combined with tandem mass spectrometry (UPLC/MS). The PK parameters and intestinal tissue concentration of EM alone, EM in HSWE, or with other anthraquinones in SD rats were analyzed using UPLC/MS., Results: The quality of the Zhiheshouwu samples met the quality standard of the Chinese Pharmacopoeia (Version 2020). The PK results showed that compared with EM alone, C max (239.90 ± 146.71 vs. 898.46 ± 291.62, P < 0.001), T max (0.26 ± 0.15 vs. 12.55 ± 1.33, P < 0.001), AUC 0-t (1575.09 ± 570.46 vs. 12154.96 ± 5394.25, P < 0.001), and AUC 0-∞ (4742.51 ± 1837.62 vs. 37131.34 ± 21647.39, P < 0.001) of EM in HSWE were decreased due to PH and EMG, while the values of V d (380.75 ± 217.74 vs. 11.75 ± 7.35, P < 0.001), T 1/2 (10.81 ± 1.99 vs. 6.65 ± 2.76, P < 0.05) and CL (19.30 ± 7.82 vs. 2.78 ± 1.88, P < 0.001) of EM in HSWE were increased due to PH and AE. In addition, the intestinal tissue concentration of emodin in HSWE was decreased compared with that of EM alone in 20 and 780 min (25.37 ± 5.98 vs. 43.29 ± 4.16 and 26.72 ± 4.03 vs. 43.40 ± 14.19, respectively. P < 0.05) dominantly due to RH and PH., Conclusion: In conclusion, compared with treatment of EM alone, the AUC 0-t value of EM in HSWE was decreased with different ways in rats. PH shortened T max , and increased V d and CL. While AE prolonged T 1/2 of EM. This indicated that the other anthraquinones in HSWE changed the PK of EM in rats and participated in the complex effects of EM on liver cancer. Besides the other anthraquinones, other components (e.g., 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside) in Zhiheshouwu may contribute in the pharmacokinetic and pharmacodynamic interactions with EM for anti-liver cancer., 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 The Authors. Published by Elsevier B.V. All rights reserved.)

Aim: This study investigated the association between nerve conduction velocity (NCV) and bone mineral density (BMD) in patients with type 2 diabetes mellitus (T2DM)., Methods: This study retrospectively collected medical data of T2DM patients who underwent dual-energy X-ray absorptiometry and nerve conduction study at the Shanghai Ruijin Hospital, Shanghai, China. The primary outcome was the total hip BMD T-score. The main independent variables were motor nerve conduction velocities (MCVs), sensory nerve conduction velocities (SCVs), and composite Z-scores of MCV and SCV. T2DM patients were divided into total hip BMD T-scores < -1 and total hip BMD T-scores ≥ -1 groups. The association between the primary outcome and main independent variables was evaluated by Pearson bivariate correlation and multivariate linear regression., Results: 195 female and 415 male patients with T2DM were identified. In male patients with T2DM, bilateral ulnar, median, and tibial MCVs and bilateral sural SCVs were lower in the total hip BMD T-score < -1 group than T-score ≥ -1 group (P < 0.05). Bilateral ulnar, median, and tibial MCVs, and bilateral sural SCVs showed positive correlations with total hip BMD T-score in male patients with T2DM (P < 0.05). Bilateral ulnar and tibial MCVs, bilateral sural SCVs, and composite MCV SCV and MSCV Z-scores were independently and positively associated with total hip BMD T-score in male patients with T2DM, respectively (P < 0.05). NCV did not show significant correlation with the total hip BMD T-score in female patients with T2DM., Conclusion: NCV showed positive association with total hip BMD in male patients with T2DM. A decline in NCV indicates an elevated risk of low BMD (osteopenia/osteoporosis) in male patients with T2DM., 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 Chen, Wang, Pan, Zhang, Zhu, Jiang, Kong, Xie, Sun, Tao, Liu and Zhao.)

The complete mitochondrial DNA genome of Devario interruptus was sequenced on the Illumina HiSeq platform and found to be 16,735 bp and included 37 genes encoding 13 proteins, 22 tRNAs, two rRNAs, and two non-coding regions. The proportion of nucleotides in mitochondrial genome was T (27.9%), C (23.7%), A (33%), G (15.4%), and the deviation of AT was 60.9%. A Maximum-Likelihood phylogenetic tree was reconstructed using the concatenated mitochondrial protein-coding genes of D. interruptus and other 18 species of fishes. Phylogenetic analysis results supported that D. interruptus was closely related to Devario shanensis . Fundamental genetic data of D. interruptus will be essential for further genetic studies., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Here, we sequenced the complete mitogenome of Rhinogobius szechuanensis using the Illumina HiSeq platform and submitted the genome to Genbank with accession number OM617727. Assembly circular mitogenome (16,492 bp) consisted of 54.4% AT content, 13 protein-coding genes, 22 tRNA genes, two rRNA genes, an origin of light-strand replication, and a control region. Phylogenetic analysis supported that R. szechuanensis was grouped with R. rubromaculatus and clustered with other Rhinogobius species. The basal molecular data will be essential for further genetics studies such as evolution, taxonomy, DNA barcoding, and population genetics of Rhinogobius., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Mitosis is a complicated and ordered process with high energy demands and metabolite fluxes. Cytosolic creatine kinase (CK), an enzyme involved in ATP homeostasis, has been shown to be essential to chromosome movement during mitotic anaphase in sea urchin. However, it remains elusive for the molecular mechanism underlying the recruitment of cytosolic CK by the mitotic apparatus. In this study, Fam96b/MIP18, a component of the MMXD complex with a function in Fe/S cluster supply, was identified as a brain-type CK (CKB)-binding protein. The binding of Fam96b with CKB was independent of the presence of CKB substrates and did not interfere with CKB activity. Fam96b was prone to oligomerize via the formation of intermolecular disulfide bonds, while the binding of enzymatically active CKB could modulate Fam96b oligomerization. Oligomerized Fam96b recruited CKB and the MMXD complex to associate with the mitotic spindle. Depletion of Fam96b or CKB by siRNA in the HeLa cells led to mitotic defects, which further resulted in retarded cell proliferation, increased cell death and aberrant cell cycle progression. Rescue experiments indicated that both Fam96b oligomerization and CKB activity were essential to the proper formation of mitotic spindle. These findings suggest that Fam96b may act as a scaffold protein to coordinate the supply and homeostasis of ATP and Fe/S clusters during mitosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Since metastasis remains the primary reason for colorectal cancer (CRC) associated death, a better understanding of the molecular mechanism underlying CRC metastasis is urgently needed. Here, we elucidated the role of Cathepsin C (CTSC) in promoting CRC metastasis. The expression of CTSC was detected by real-time PCR and immunohistochemistry in the human CRC cohort. The metastatic capacities of CTSC-mediated metastasis were analyzed by in vivo metastasis model. Elevated CSTC expression was positively associated with tumor differentiation, tumor invasion, lymph node metastasis, and AJCC stage and indicated poor prognosis in human CRC. CTSC overexpression in CRC cells promoted myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) recruitment by the CSF1/CSF1R axis. In contrast, the knockdown of CSF1 reduced CTSC-mediated MDSCs and TAMs infiltration and CRC metastasis. Depletion of either MDSCs or TAMs decreased CTSC-mediated CRC metastasis. In human CRC tissues, CTSC expression was positively associated with intratumoral MDSCs and TAMs infiltration. Furthermore, the combination of CTSC inhibitor AZD7986 and anti-PD-L1 antibody blocked CTSC-induced CRC metastasis. CTSC overexpression promoted MDSCs and TAMs infiltration by CSF1/CSF1R axis. Interruption of this oncogenic loop may provide a promising treatment strategy for inhibiting CTSC-driven CRC metastasis.

Ethnopharmacology Relevance: Sophora flavescens is a frequently used traditional Chinese medicine (TCM) for the treatment of skin disorders, diarrhea, vaginal itching and inflammatory diseases. In particular, the root of S. flavescens combination with other herbs mainly treat eczema ailment in the clinical applications. However, a holistic network pharmacology approach to understanding the mechanism by which alkaloids in S. flavescens treat eczema has not been pursued., Aim of the Study: To examine the network pharmacological potential effect of S. flavescens on eczema, we studied the alkaloids, performed protein targets prediction and investigated interacting signal pathways. Furthermore, animal experiment was carried out to evaluate its efficacy and real-time quantitative polymerase chain reactions (RT-qPCR) analysis was explored the mechanism of action., Materials and Methods: The detail information on alkaloids from S. flavescens were obtained from a handful of public databases on the basis of oral bioavailability (OB ≥ 30%) and drug-likeness (DL ≥ 0.18). Then, correlations between compounds and protein targets were linked using the STRING database, and targets associated with eczema were gathered by the GeneCards database. Human genes were identified and subjected to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and Gene Ontology (GO) functional enrichment analysis. Particularly, matrine, the crucial alkaloid from S. flavescens, was estimated using a 2,4-dinitrochlorobenzene (DNCB)-induced eczema Kunming (KM) mice model, administered (50 mg/kg and 10 mg/kg) to mice for 22 days. On the last day, the activities of serum tumor necrosis factor α (TNF-α), interleukin-4 (IL-4) and histopathologic examinations were determined. For further to elucidate the mechanisms, the mRNA levels of TNF-α, STAT3, TP53, AKT1, IL-6, JUN and EGFR in dorsal skin tissues were also tested., Results: Network analysis collected and identified 35 alkaloids from S. flavescens. Among them, in total 10 dominating alkaloids, including matrine, oxymatrine, sophoridine, sophocarpine, oxysophocarpine, allomatrine, sophoramine, anagyrine, cytisine and N-methylcytisine. And 71 related targets were provided of alkaloids for the treatment of eczema from S. flavescens. Furthermore, matrine dose-dependently (50 or 10 mg/kg, 22 days, apply to dorsal skin) remarkable decreased the serum levels of TNF-α and IL-4, and significantly alleviated the skin lesions. The effects of 50 mg/kg of matrine were almost identical to those of 200 mg/kg of the positive drug dexamethasone (DXM). The further RT-qPCR analyses could reveal that matrine down-regulate TNF-α, STAT3 and TP53 at transcriptional level in dorsal skin tissues., Conclusion: Pharmacological network analysis can utilize to illuminate the pharmacodynamic substances and the potential molecular mechanism of S. flavescens for treating eczema. Matrine, as the crucial alkaloid from S. flavescens, could be a promising drug candidate for the treatment of eczema ailment., Competing Interests: Declaration of competing interest The authors do not have any conflicts of interest to disclose., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: To study the risk factors of adverse pregnancy outcomes for the diagnosis and treatment of pregnancy after cesarean section complicated with placenta previa. Methods: A national multicenter retrospective study was conducted to select a total of 747 pregnant women with the third trimester singleton pregnancy after cesarean section complicated with placenta previa from 12 tertiary hospitals in January 1st to December 31st, 2018. The risk factors of severe adverse outcomes [hysterectomy, intraoperative blood loss ≥1 000 ml, intraoperative diagnosis of placenta accreta spectrum disorders (PAS)] in pregnant women with second pregnancy complicated with placenta previa after cesarean section were investigated by logistic regression analysis. The roles of prenatal ultrasonography and magnetic resonance imaging (MRI) in the prediction of PAS and severe adverse outcomes were observed. According to whether vascular intervention was performed (uterine artery embolization or abdominal aortic balloon occlusion), the pregnant women were divided into the blocked group and the unblocked group, and the maternal and infant perinatal outcomes between the two groups were compared. Results: (1) General information: the hysterectomy rate of 747 pregnant women with second pregnancy complicated with placenta previa after cesarean section was 10.4% (78/747), the intraoperative blood loss ≥1 000 ml in 55.8% (417/747), and PAS was confirmed in 47.5% (355/747). The incidence of uterine rupture was 0.8% (6/747). (2) Analysis of risk factors for severe adverse outcomes: based on binary unconditioned logistic regression univariate and multivariate analysis, the risk factors for hysterectomy were the mode of vascular embolization and intraoperative blood loss. The probability of hysterectomy with uterine artery embolization was 5.319 times higher than that with abdominal aortic balloon occlusion (95% CI : 1.346-21.018). The risk factors of intraoperative blood loss ≥1 000 ml were the number of cesarean section delivery, ultrasonography indicated PAS and suspected PAS, intraoperative PAS and complete placenta previa. The risk factors for intraoperative PAS were uterine scar thickness, ultrasonography indicated PAS and suspected PAS, MRI indicated PAS and suspected PAS, and complete placenta previa. (3) The roles of ultrasonography and MRI in predicting PAS: the sensitivity and specificity of ultrasonography in predicting PAS were 47.5% and 88.4%; the kappa value was 0.279 ( P <0.001), with fair agreement. The sensitivity and specificity of MRI to predict PAS were 79.2% and 97.8%, respectively. The kappa value was 0.702 ( P <0.001), indicating a good agreement. The intraoperative blood loss and hysterectomy rate of pregnant women with PAS indicated by ultrasonography and MRI were significantly higher than those with PAS only by ultrasonography or MRI. (4) Influence of vascular occlusion on pregnancy outcome: there were no significant differences in intraoperative blood loss and incidence of intraoperative bleeding ≥1 000 ml between the blocked group and the unblocked group (all P >0.05). There was no significant difference in intraoperative blood loss between the pregnant women with abdominal aortic balloon occlusion, uterine artery embolization and those without occlusion ( P =0.409). The hysterectomy rate of pregnant women with uterine artery embolization was significantly higher than those with abdominal aortic balloon occlusion [39.3% (22/56) vs 10.0% (5/50), P =0.001]. Conclusions: In the third trimester of pregnancy with placenta previa after cesarean section, MRI examination has better consistency in predicting PAS than ultrasonography examination. Ultrasonography examination combined with MRI examination could effectively predict the hysterectomy rate and intraoperative blood loss. Vascular occlusion could not reduce the amount of intraoperative blood loss. The hysterectomy rate of pregnant women with uterine artery embolization is higher than those with abdominal aortic balloon occlusion.

Background: The results of halo sign in the differential diagnosis of thyroid nodules were conflicting, and the value of contrast-enhanced ultrasound (CEUS) in characterization of thyroid nodules with halo has not been fully evaluated. This study was therefore designed to investigate the value of contrast-enhanced ultrasound features in the differential diagnosis of thyroid nodules with halo sign on B-mode ultrasound., Material and Methods: Seventy-four consecutive thyroid nodules with halo sign on B-mode ultrasound were pathologically confirmed by surgery or fine needle aspiration, including 43 benign and 31 malignant lesions. All these lesions underwent pre-operative CEUS examination. The CEUS features, including enhanced time, enhanced intensity and homogeneity, and presence of enhancing ring, were compared between benign and malignant ones., Results: Enhanced intensity was significant different between benign and malignant lesions with halo. Hypo-enhancement was more frequently detected in malignant nodules than that in benign ones, compared with iso-enhancement and hyper-enhancement (p = 0.013, and = 0.014, respectively). Detection rate of high-enhancing ring was significantly higher in benign nodules than that in malignant group (p = 0.001). While in nodules > 10 mm, only high-enhancing ring was the distinguishing feature between benign and malignant nodules., Conclusions: Enhanced intensity and high-enhancing ring may be helpful in the differential diagnosis of thyroid nodules with halo sign on B-mode ultrasound., (© 2023. The Author(s).)

The tuberous root of Ophiopogon japonicus (Thunb.) Ker-Gawl. is a well-known Chinese medicine also called Maidong (MD) in Chinese. It could be divided into "Chuanmaidong" (CMD) and "Zhemaidong" (ZMD), according to the geographic origins. Meanwhile, the root of Liriope spicata (Thunb.) Lour. var. prolifera Y. T. Ma (SMD) is occasionally used as a substitute for MD in the market. In this study, a reliable pressurized liquid extraction and HPLC-DAD-ELSD method was developed for the simultaneous determination of nine chemical components, including four steroidal saponins (ophiopojaponin C, ophiopogonin D, liriopesides B and ophiopogonin D'), four homoisoflavonoids (methylophiopogonone A, methylophiopogonone B, methylophiopogonanone A and methylophiopogonanone B) and one sapogenin (ruscogenin) in CMD, ZMD and SMD. The method was validated in terms of linearity, sensitivity, precision, repeatability and accuracy, and then applied to the real samples from different origins. The results indicated that there were significant differences in the contents of the investigated compounds in CMD, ZMD and SMD. Ruscogenin was not detected in all the samples, and liriopesides B was only found in SMD samples. CMD contained higher ophiopogonin D and ophiopogonin D', while the other compounds were more abundant in ZMD. Moreover, the anticancer effects of the herbal extracts and selected components against A2780 human ovarian cancer cells were also compared. CMD and ZMD showed similar cytotoxic effects, which were stronger than those of SMD. The effects of MD may be due to the significant anticancer potential of ophiopognin D' and homoisoflavonoids. These results suggested that there were great differences in the chemical composition and pharmacological activity among CMD, ZMD and SMD; thus, their origins should be carefully considered in clinical application.

We reported the manifestations, auxiliary examination, and treatment courses of a case of scimitar syndrome with pulmonary sequestration containing carcinoma. The clinical characteristics of scimitar syndrome with pulmonary sequestration, pulmonary sequestration containing carcinoma were summarized based on the data of this case and the related literatures before January 2022. Scimitar syndrome can coexist with ipsilateral pulmonary sequestration. Because sequestered lung tissue has a risk of malignant transformation, a cancer screening test is useful for early diagnosis and timely treatment.

Introduction: This study aimed to investigate the relationship between Oxford Classification scores and longitudinal changes in proteinuria in patients with immunoglobulin A nephropathy (IgAN)., Methods: The study was a single-center retrospective cohort study involving 358 patients with primary IgAN who were treated at the Shenzhen Second People's Hospital, China, between January 2011 and May 2021. Multivariate linear regression and generalized additive mixed models (GAMMs), adjusted for traditional risk confounders, were used to evaluate the correlation between scores for mesangial hypercellularity (M), endocapillary hypercellularity (E), segmental glomerulosclerosis (S), tubular atrophy/interstitial fibrosis (T), and crescents (C) (known as the Oxford Classification MEST-C score system), with proteinuria/creatinine ratio (PCR) at the time of renal biopsy and longitudinal changes in PCR, respectively., Results: The median PCR was 1061 mg/g, and it increased on average by 68.82 mg/g per year in these patients. Among patients with renal insufficiency, compared with patients without relative lesions, those with E present (E1) (1153.44; 95% confidence interval [CI], 188.99-2117.89 mg/g) and C > 0 (C1/2) (1063.58; 95% CI, 185.25-1941.90 mg/g) were associated with increased PCR levels at the time of renal biopsy. What's more, S present (S1) (194.96; 95% CI, 54.50-335.43 mg/g per year) was associated with the fastest PCR increase; C > 0 (C1/2) (147.59; 95% CI, 8.32-286.86 mg/g per year) and T >25% (T1/2) (77.04; 95% CI, 7.18-146.89 mg/g per year), were also correlated with a faster PCR increase. In patients with normal kidney function, associations between S1 (55.46; 95% CI, 8.93-101.99 mg/g per year) and E1 (94.02; 95% CI, 21.47-166.58 mg/g per year) and PCR change could be observed. Additionally, in patients with overweight/obesity, S1 (156.09; 95% CI, 52.41-259.77 mg/g per year), E1 (143.34; 95% CI, 35.30-251.38 mg/g per year), T1/2 (116.04; 95% CI, 22.58-209.51 mg/g per year), as well as C1/2 (134.03; 95% CI, 41.73-226.32 mg/g per year) were associated with noticeably quicker PCR increase., Conclusions: Overall, E1 and C1/2 were independently associated with raised proteinuria levels at the time of renal biopsy, and S1, E1, T1/2, C1/2 were independently associated with a longitudinal increase in proteinuria in the patients with IgAN, especially in those with renal insufficiency or overweight/obesity, suggesting that currently available treatments might not be satisfactory, and weight control might be beneficial. Individual therapy development might benefit from the use of the Oxford Classification system., Competing Interests: Author X-LC is employed by Empower U, X&Y solutions Inc. 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 © 2023 Xu, Guo, Cao, Xu, Liao, Chen, Song, Chen, Guan, Tang, Xiang, Chen and Wan.)

Background: Exosomes exert considerable influence in mediating regulatory T (Treg) cells differentiation, which attach great importance to attenuating acute cellular rejection after liver transplantation (LT). And, miRNAs are known to play essential roles in cell-cell communication delivered by exosomes. However, the function of exosomal miRNAs in regulating Treg cells after LT remains unknown. Here, we performed an expression profiling analysis of exosome-miRNAs from human plasma after LT and investigated their immunoregulatory effects on Treg cells., Methods: Fifty-eight LT patients and nine donors were included in this report. miRNA profiles in plasma exosomes were analyzed using next-generation sequencing. Flow cytometry, HE and multiplex immunofluorescent staining were used to identify Treg cells in the liver and peripheral blood. A lentiviral vector system was used to overexpress miR-193b-3p in dendritic cells (DCs), and exosomes isolated from these transfected cells were co-cultured with spleen lymphocytesin vitro. A quantitative Real-time PCR and enzyme-linked immunosorbent assay were used to detect the expression of cytokines., Results: Treg cell infiltration was increased in the liver along with Th17 and CD8+ T cell, and it was down-regulated in peripheral blood in the acute rejection group. High-throughput sequencing revealed that miR-193b-3p was markedly up-regulated in plasma exosomes of non-rejection LT patients. The NLRP3 inflammasome was screened as a target for miR-193b-3p based on target prediction and functional enrichment analyses. Exosomal miR-193b-3p derived from DCs increased Treg cells as demonstrated in vitro. miR-193b-3p overexpression down-regulated NLRP3 as well as the inflammatory cytokines IL-1β and IL-17A while increasing levels of the cytokines IL-10 and TGF-β., Conclusion: DC derived exosomal miR-193b-3p promoted Treg cells by inhibiting NLRP3 expression. These findings not only provide a new perspective on the mechanisms, but also hold great promise for the treatment or prevention of liver allograft rejection., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Purpose: Blood transfusion is a common and life-saving procedure in congenital heart surgery (CHS), and it is critical for patients to identify risk factors prior to surgery. Our objective is to conduct an analysis of the preoperative factors that influence blood use during CHS and to offer guidance on preoperative blood preparation., Methods: A total of 1550 cases were retrospectively analyzed in our institution between May 2019 and June 2020. We determined whether to employ red blood cells (RBCs), platelets, and plasma as dependent variables; we treated the data from characteristics and laboratory tests as binary data, except for the Risk Adjustment for Congenital Heart Surgery (RACHS) methods as multinomial data, and finally taken into binary logistic regression analysis., Results: The total amounts of transfused RBCs, platelets, and plasma were 850.5 U (N = 713, 46%), 159 U (N = 21, 1.4%), and 1374.2 U (N = 953, 61.5%), respectively. Multivariate analysis found age (OR 0.142, 95% CI 0.099-0.203, P < 0.001), weight (0.170, 0.111-0.262, P < 0.001) RACHS method (RACHS2 vs. RACHS1, 3.444, 2.521-4.704, P < 0.001; RACHS3 vs. RACHS1, 9.333, 4.731-18.412, P < 0.001; RACHS4 vs. RACHS1, 31.327, 2.916-336.546, P = 0.004), and hemoglobin (0.524, 0.315-0.871, P = 0.013) to be independent risk predictors of RBC transfused volume; age (9.911, 1.008-97.417, P = 0.049), weight (0.029, 0.003-0.300, P = 0.029), RACHS method (RACHS3 vs. RACHS1, 13.001, 2.482-68.112, P = 0.002; RACHS4 vs. RACHS1, 59.748, 6.351-562.115, P < 0.001) to be platelets; and age (0.488, 0.352-0.676, P < 0.001), weight (0.252, 0.164-0.386, P < 0.001), RACHS method (RACHS2 vs. RACHS1, 2.931, 2.283-3.764, P < 0.001; RACHS3 vs. RACHS1, 10.754, 4.751-24.342, P < 0.001), APTT (1.628, 1.058-2.503, P = 0.027), and PT (2.174, 1.065-4.435, P = 0.033) to be plasma., Conclusion: Although patients' age, weight, routine blood test, coagulation function, and protein levels should all be considered for preparing blood before CHS, the RACHS method is the most important factor influencing intraoperative blood transfused volume and should be considered first in clinical blood preparation., (© 2022. The Author(s).)

A novel U(VI)-containing polytungstate (U-POW) tetramer, {K 1.37 Na 26.63 [K 2 (UO 2 ) 4 Cl 0.5 (OH) 5.5 (γ-SiW 10 O 36 ) 4 ]}·ca66H 2 O ( U 4 ), was synthesized using the Keggin-type precursor [γ-SiW 10 O 36 ] 8- and UO 2 (NO 3 ) 2 . U 4 was further characterized by single-crystal X-ray diffraction, FT-IR, Raman spectroscopy, solid-state diffuse reflection spectroscopy, ICP-OES, ESI-MS, TGA, and PXRD. The central {K 2 (UO 2 ) 4 Cl 0.5 (OH) 5.5 } chromophore was constructed dexterously from four uranyl, four halves of K ions, 5.5 bridging μ 2 -OH, and disordered Cl ions, and was further stabilized by four {γ-SiW 10 } moieties to construct the tetramer [K 2 (UO 2 ) 4 Cl 0.5 (OH) 5.5 (γ-SiW 10 O 36 ) 4 ] 28- . Notably, U 4 could work as an effective bifunctional Lewis acid-base catalyst for the synthesis of pyrazoles via the condensation of hydrazines with 1,3-diketones under mild conditions, which is attributed to the synergetic effect of the Lewis acidity of U(VI) and the Lewis basicity of {γ-SiW 10 }.

Paris spp. are important medicinal plant and main raw material for many Chinese patent medicines, but viral diseases have became serious problems in cultivation of this group of important medicinal plants in China. In this study, eight viruses were identified in the diseased plants of Paris yunnanensis by high-throughput sequencing (HTS) and RT-PCR. These viruses include three novel viruses (two potyviruses and one nepovirus), Hippeastrum chlorotic ringspot virus (HCRV), Lychnis mottle virus (LycMoV), Paris mosaic necrosis virus (PMNV), Paris virus 1 and pepper mild mottle virus. The three new viruses were tentatively named Paris potyvirus 3 (ParPV-3), Paris potyvirus 4 (ParPV-4), Paris nepovirus 1 (ParNV-1) and their complete genome sequences were determined. Sequence analyses showed ParPV-3 and ParPV-4 shared the highest amino acid (aa) sequence identities of 54.3% to each other and 53.0-57.8% to other known potyviruses. ParNV-1 had aa sequence identities of 28.8-63.7% at protease-polymerase (Pro-Pol) with other nepoviruses. Phylogenetic analyses further support that the three viruses are new members of their corresponding genera. Analyses of the partial sequences of HCRV and LycMoV infecting P. yunnanensis revealed they diverged from existing isolates by aa sequence identities of 97.1% at glycoprotein precursor of HCRV and 93.3% at polyprotein of LycMoV. These two viruses are reported for the first time in Paris spp. A total of 123 field samples collected from P. yunnanensis in four counties of Yunnan, Southwest China were tested by RT-PCR for detecting each of the eight viruses. Results showed that nearly half of the samples were positive for at least one of the eight viruses. Two potyviruses, ParPV-3 (26.8%) and PMNV (24.4%), were predominant and widely distributed in the fields, while other viruses occurred in low rates and/or had limited distribution. This study insights into the virome infecting P. yunnanensis and provides valuable information for diagnosis and control of viral diseases in P. yunnanensis., Competing Interests: G-hZ was employed by Chinese Medicine Resources 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 © 2022 Lan, He, Yang, Zhou, Chen, Wei, Li, Gu, Li and Li.)

The synthesis of ionic olefin linked three-dimensional covalent organic frameworks (3D COFs) is greatly challenging given the hardness of the formation of stable carbon-carbon double bonds (-C = C-). Herein, we report a general strategy for designing porous positively charged sp 2 carbon-linked 3D COFs through the Aldol condensation promoted by quaternization. The obtained 3D COFs, namely TFPM-PZI and TAPM-PZI, showed impressive chemical stability. Furthermore, the positively charged frameworks with regular porosity endow 3D ionic COFs with selective capture radioactive ReO 4 - /TcO 4 - and great removal efficiency in simulated Hanford waste. This research not only broadens the category of 3D COFs but also promotes the application of COFs as efficient functional materials., (© 2022. The Author(s).)

Background: Prognosis varies among stage IV colorectal cancer (CRC). Our study aimed to build a robust prognostic nomogram for predicting overall survival (OS) of patients with stage IV CRC in order to provide evidence for individualized treatment., Method: We collected the information of 16,283 patients with stage IV CRC in the Surveillance, Epidemiology, and End Results (SEER) database and then randomized these patients in a ratio of 7:3 into a training cohort and an internal validation cohort. In addition, 501 patients in the Sixth Affiliated Hospital of Sun Yat-sen University (Guangzhou, China) database were selected and used as an external validation cohort. Univariate and multivariate Cox analyses were used to screen out significant variables for nomogram establishment. The nomogram model was assessed using time-dependent receiver-operating characteristic curve (time-dependent ROC), concordance index (C-index), calibration curve, and decision curve analysis. Survival curves were plotted using the Kaplan-Meier method., Result: The C-index of the nomogram for OS in the training, internal validation, and external validation cohorts were 0.737, 0.727, and 0.655, respectively. ROC analysis and calibration curves pronounced robust discriminative ability of the model. Further, we divided the patients into a high-risk group and a low-risk group according to the nomogram. Corresponding Kaplan-Meier curves showed that the prediction of the nomogram was consistent with the actual practice. Additionally, model comparisons and decision curve analysis proved that the nomogram for predicting prognosis was significantly superior to the tumor-node-metastasis (TNM) staging system., Conclusions: We constructed a nomogram to predict OS of the stage IV CRC and externally validate its generalization, which was superior to the TNM staging system., (© The Author(s) 2022. Published by Oxford University Press and Sixth Affiliated Hospital of Sun Yat-sen University.)

In this paper, we first report the complete mtDNA sequence of Opsarius caudiocellatus with the main aim of providing a basis for further researches of this species. Assembly circular mitogenome was 16,534 bp long encoded 13 protein-coding genes, two ribosomal RNA genes, 22 transfer RNA genes, and one control region. The gene nucleotide composition was estimated to be 28.1% A, 25.2% T, 18.6% G, 28.1% C. A maximum-likelihood (ML) phylogenetic tree was reconstructed using the 13 concatenated mitochondrial protein-coding genes of O. caudiocellatus and other 19 species of the subfamily Chedrinae. Result of the phylogenetic analysis revealed that O. caudiocellatus was well grouped with Barilius barila. This study could enrich genetic resources and be helpful to studies on evolution and conservation genetics for O. caudiocellatus., Competing Interests: The authors declare no potential conflict of interest., (© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Objective: To explore the correlation between the changes of T lymphocyte subsets and cytokines in patients with MM and immune function status, biochemical indicators, and their relationships with clinical stage and prognosis, which is expected to provide a scientific basis for the prognosis analysis and condition monitoring of MM patients., Methods: The clinical data of 89 MM patients in two hospitals were collected, and 36 healthy people without tumor or infectious diseases were selected as the control group. Flow cytometry and enzyme-linked immunosorbent assay (ELISA) were used to detect the changes of core members of peripheral blood T lymphocyte subsets and cytokine levels, respectively. At the same time, automatic biochemical analyzer and automatic blood cell analyzer were used to detect serum β 2 -microglobulin (β 2 -MG), lactate dehydrogenase (LDH), albumin (ALB), creatinine (CRE) and hemoglobin (HGB) levels, and the relationship between T lymphocyte subsets and the above indexes and their clinical significance were analyzed., Results: The proportions of NK cells and CD8 + T lymphocytes in the peripheral blood of MM patients were significantly higher than that of the control group ( P <0.01), the proportion of CD4 + T and the ratio of CD4 + /CD8 + were lower than those of the control group ( P <0.05); however, there was no significant difference in the numbers CD3 + T cells compared with the control group ( P >0.05). The proportion of CD4 + T and ratios of CD4 + /CD8 + in MM patients were lower than those of normal controls, and were negatively correlated with MM staging ( r =-0.964, r =-0.653), that is, the later the MM staging, the more obvious their levels were reduced, while CD8 + T and NK cells were positively correlated with MM staging ( r =0.891, r =0.728), that is, the later the MM staging, the more significant their levels increased. The levels of Treg cells (CD4 + CD25 high CD127 low/- T cells/CD4 + T cells) of MM patients in the disease stage Ⅰ, Ⅱ and Ⅲ were (5.87±0.92)%, (7.97±1.32)%, (11.52±4.71)% respectively, the difference was statistically significant compared with control group ( P <0.05), and the level of Treg cells in MM patients with stage III was significantly higher than that in controls and patients with other disease stages ( P <0.01). The proportion of Treg cells (CD4 + CD25 high CD127 low/- T cells/CD4 + T cells) in MM patients was positively correlated with the concentration of β 2 -MG and LDH ( r =0.793, r =0.536), but had no significant correlation with HGB, ALB and CRE. The serum levels of IL-6, IL-10 and TNF-α in MM patients were significantly higher than those in the control group ( P <0.05), which were closely related to MM staging( r =0.839, r =0.917, r =0.746), that is, the later the MM staging, the higher the levels; The serum IFN-γ level was negatively correlated with the stage of MM ( r =-0.689), and its level gradually decreased with the increase of the disease stage and degree ( P <0.01). There was no significant correlation between the levels of IL-2 and IL-4 and the disease stage, but they were all up-regulated compared with the control group ( P <0.05)., Conclusion: The abnormal regulation of the core members of T lymphocyte subsets and the levels of various cytokines are closely related to the disease progression and poor prognosis of MM patients, which is an effective indicator for the disease monitoring of MM patients.

Minimal persistent inflammation (MPI), the local inflammation that occurs after an acute type II immune response in patients with allergic rhinitis (AR), is responsible for airway hyperreactivity and the recurrence of AR. Innate lymphoid cells (ILCs) play a crucial role in mucosal immune homeostasis, but the changes of ILC subsets in the MPI stage remain unclear. In this study, the levels of ILC-secreting cytokines in nasal lavages were analyzed from 19 AR patients and 8 healthy volunteers. AR and MPI model mice were established to study the ILC subsets. The results showed that IL-17A was significantly increased in nasal lavage of AR patients in the MPI stage by MSD technology. When compared with the AR model mice, the frequency of IL-13 + ILC2 in the nasal mucosa and lungs decreased, while IL-5 + ILC2 remain high in MPI model mice. A part of the IL-5 + ILC2 subset displayed ILC3-like characteristics with elevated RORγt, IL-17A and IL-23R expression. Especially, these ILC3-like ILC2 exhibited up-regulation of GATA3 + RORγt + were increased in MPI model mice. After the treatment of Biminkang, the frequencies of IL-5 + ILC2, IL-17A + ILC3, and GATA3 + RORγt + ILC3-like ILC2 were significantly reduced, and IL-23R expression was also decreased on ILC3-like-ILC2 subset. These results suggested that the elevated IL-17A in the MPI stage has been related to or at least partly due to the increased of ILC3-like ILC2. Biminkang could effectively decrease IL-17A + ILC3 and inhibit ILC3-like ILC2 subset in the MPI stage. Biminkang is effective in administrating MPI by regulating airway ILC homeostasis., (© 2022 Society for Leukocyte Biology.)

Statolith is one of the most important hard tissues to study the age, growth, population structure and life history of cephalopods. In order to stuty statolith microstructure and growth characteristics of Sthenoeuthis oualaniensis in the northwest Indian Ocean, 1009 samples were collected by Chinese light falling-net fishery fleets during investigation and production in the northwest Indian Ocean from February to May of 2019. Total statolith length (TSL), lateral dome length (LDL), wing length (WL) and maximum width (MW) were taken as the indicators of morphological feature of the statolith, combined with the age data, the statolith microstructure and growth characteristics of S. oualaniensis were studied. The results showed that the statolith microstructure could be divided into postnuclear zone, dark zone and peripheral zone according to the width of growth increment. The analysis of covariance showed that there was no growth difference of TSL, LDL, WL and MW between different sexes. The relationships between TSL, WL, MW and age were best described by the power functions, while the relationship between LDL and age was best described by the linear function. In general, with the increase of age, the instantaneous relative growth rate and absolute growth rate of TSL, WL, LDL and MW decreased, and 140-180 d may be the age of sexual maturity for this squid.

Background: The benefit of adjuvant chemotherapy (AC) for patients with stage II gastric cancer remains controversial. This study aimed to explore the indications for adjuvant chemotherapy in patients with stage II gastric cancer by constructing an individual prediction model., Patients and Methods: In this Chinese multicenter study, a total of 1012 patients with stage II gastric cancer after D2 radical gastrectomy were retrospectively analyzed. All patients were randomly assigned to a training cohort (n = 674) or a validation cohort (n = 338). A nomogram was constructed according to the training cohort. Concordance index (C-index), the area under the receiver operating characteristic (ROC) curves (AUC), calibration curves, and decision curve analysis (DCA) were applied to evaluate the performance of the nomogram. ROC curves and stratified survival were used to determine the patients' cutoff score for a benefit from adjuvant chemotherapy. An additional 338 patients were used as a validation cohort to validate the feasibility of using this nomogram to guide individualized therapy for patients with stage II gastric cancer., Results: Univariate and multivariate analyses illustrated that age, sex, tumor location, size, carcinoembryonic antigen (CEA), hemoglobin (HB), and T stage were independent prognostic factors for overall survival (OS), and they were used to establish a nomogram. The cutoff value was determined by ROC curve analysis, and patients were divided into a high-risk group (< 239 points) and a low-risk group (≥ 239 points). There was no significant difference in the OS of low-risk patients in either the training cohort or the validation cohort. However, the OS of high-risk patients in the AC group was better than that of patients in the surgery-only group., Conclusions: This prediction model can be applied to guide treatment of patients with stage II gastric cancer. High-risk patients (< 239 points) are likely to benefit from AC after D2 radical gastrectomy., (© 2022. Society of Surgical Oncology.)

Background: To evaluate the prognostic value of frailty in older recipients of concomitant valve replacement (VR) and bipolar radiofrequency ablation (BRFA), we examined whether clinical and functional outcomes differed between frail and non-frail groups of older patients referred for concomitant VR and BRFA., Methods: In a single-center retrospective observational cohort study, we compared the clinical and functional outcomes in frail versus non-frail patients. Frailty was assessed using the 5-item Cardiovascular Health Study (CHS) frailty scale. Patients were divided into two groups, frail and non-frail. Functional outcome was assessed using the internationally validated Atrial Fibrillation Effect on QualiTy-of-Life (AFEQT) questionnaire., Results: We enrolled 185 patients aged ≥ 65 years who underwent concomitant VR and BRFA. About 36.2% (n = 67) of the patients were included in the frail group and the remaining patients (n = 118) in the non-frail group. Follow-up was complete with a median duration of 58 months (interquartile range 44-76 months). Significant differences were observed between the two groups with respect to postoperative pulmonary complications (frail vs. non-frail patients, 50.74% vs. 22.9%, respectively, P < .001) and hospital mortality (10.45% vs. 1.69%, respectively, P = .021). The frail group had a higher adjusted risk for all-cause mortality (adjusted HR 4.06; 95% CI 1.33 to 12.38; P = .014) and all-cause hospitalization (adjusted HR 2.24; 95% CI 1.12 to 4.50; P = .023). Frailty was associated with lower overall AFEQT scores at baseline (Estimate, - 0.400; 95% CI - 0.532 to - 0.267; P < .001). Compared to the non-frail group, the frail group continued to have lower overall AFEQT scores with no significant improvement in follow-up at 1 year and 2 years after concomitant VR and BRFA., Conclusion: Frail patients had lower baseline AFEQT scores and were more likely to have adverse outcomes from postoperative pulmonary complications, and frailty was also an independent risk factor for long-term all-cause mortality and all-cause rehospitalization. Further studies are needed to assess the impact of frailty., (© 2022. The Author(s).)

Objective: To propose the an optimal screw placement scheme to prevent femoral neck shortening, finite element analysis was used to evaluate the biomechanical outcome of different numbers formed by full threaded screws at different positions in the treatment of femoral neck fractures of Pauwels type Ⅱ., Methods: Recruited for this study was a 55-year-old female volunteer with a weight of 70 kg and a height of 165 cm. CT scan data of her right femur was collected. The models of femoral of Pauwels typeⅡ and fully threaded screw(FTS) and partially threaded screw(PTS) were constructed in three-dimensional modeling software. All these screw placement schemes were divided into eight groups simulated the inverted triangular configuration:three PTSs, an anterosuperior FTS and two PTSs, a posterosuperior FTS and two PTSs, an inferior FTS and two PTSs, an anterosuperior PTS and two FTSs, a posterosuperior PTS and two FTSs, an inferior PTS and two FTSs and three FTSs. All fracture internal fixation models were processed in finite element analysis software. Parameters of postoperative femoral neck length, displacement distribution and peak displacement of screws and VonMises stress distribution and peak stress of screws, the proximal femur and fracture section were collected., Results: The maximum VonMises stress of screws was 239.71, 213.44, 199.37, 230.82, 201.63, 215.72, 185.65 and 192.64 MPa, respectively, which was concentrated in the inferior screw near the fracture line. The maximum Von Mises stress of the proximal femur was 269.48, 241.62, 249.43, 269.69, 271.60, 346.64, 236.97 and 439.62 MPa, respectively, which was concentrated in the inferior medial area of subtrochanteric femur. The maximum Von Mises stress of fracture section was 149.12, 143.04, 140.47, 139.63, 139.81, 130.07, 117.77 and 57.89 MPa, respectively, which was concentrated around the partially threaded screw channel instead of the fully threaded screw channel. The maximum displacement of screws was 5.52, 5.43, 5.32, 5.17, 5.05, 5.13, 5.28 and 5.04 mm, respectively, which was along the axis of the femoral neck, and the displacement distribution was concentrated on the tip of the screw. The length of postoperative femoral neck length was 74.69, 74.72, 74.70, 74.70, 74.72, 74.70, 74.72 and 74.74 mm, respectively., Conclusion: The placement of one anterosuperior partially threaded screw and two fully threaded screws with an inverted triangular distribution can not only meet the sliding compression effect to promote femoral neck healing and ensure the stability of the proximal femur, but also reduce the degree of postoperative femoral neck shortening and reduce the incidence of hip joint dysfunction. This study provides a new optimal screw placement solution for the treatment of femoral neck fractures.

Cyprinid fish Barilius barila found in the Irrawaddy water system is a valuable fishery resource and has been listed as Least Concern by the IUCN. This study determined the complete mitochondrial genome of B. barila from Yunnan, China, for the first time. Circular molecule of B. barila mitogenome was sequenced to be 16,560 bp in length, with the typical gene structure of 13 protein-coding genes, 22 transfer RNA genes, two ribosomal RNA genes, and two noncoding areas (control region and the origin of L-strand replication). Overall nucleotides composition appeared to be 27.5% A, 24.8% T, 19.2% G, and 28.6% C, with a slight AT (52.3%) bias. The topology of the phylogenetic tree showed that B. barila was well grouped with Opsarius caudiocellatus, and clustered together with the genus Opsarius instead of Barilius, revealing that it was more reasonable for Barilius barila to belong to Opsarius rather than Barilius ., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Continuous process is a promising alternative for tradition batch process in biomanufacturing, which has higher productivity and lower material consumption. However, despite the maturation of necessary technologies for continuous process, there are few discussion about optimization of full continuous process. One possible reason is that the continuous process is such a complex and interacted process that the traditional experiment-based optimization approach is not sufficient anymore. To address that problem, the process simulation tool SuperPro Designer and continuous capture chromatography model were integrated into a model-assisted design platform for better development of continuous process. The influences of different continuous capture operation modes and sub-lot number under various upstream conditions were analyzed for pilot-scale production. The best combination of operation mode and sub-lot number were determined for the highest equipment utilization without any conflict. After the process optimization, the equipment utilization of continuous process was significantly improved to 27.3%. Then, a pilot-scale case study was carried out to validate the proposed approach. The results showed that the scaling up and process design of continuous process were successful. No time conflict and process failure happened and the final product met the release specification. Finally, the cost of goods was evaluated with SuperPro Designer, and the results showed a 17.4% cost reduction for optimized continuous downstream process compared to batch process, which is promoting for the future industrial 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 © 2022 Elsevier B.V. All rights reserved.)

Objective: To investigate the mutational features of the immunoglobulin heavy chain variable region (IgHV) gene in patients with chronic lymphocytic leukemia (CLL) using immunophenotypic and molecular genetic methods. Methods: The laboratory results of 266 CLL patients who underwent IgHV gene examination at Sino-US diagnostics laboratory from February 2020 to February 2021 were analyzed for the IgVH mutational status and presence of specific IgVH fragments. In addition, their immunophenotypic, molecular, chromosomal karyotypic, and FISH profiles were investigated and correlated with the IgVH mutational status. Results: Among 266 patients, 172 were male and 94 were female, with a media age of 67 years (20-82 years).There were more patients with mutated IgHV (m-IgHV) than unmutated IgHV (un-IgHV) (69.2%∶30.8%). There was association of VH family and the presence of gene fragments: the overall incidence of VH families including VH3 family (142/266, 53.4%), VH4 family (75/266, 28.2%), and VH1 family (34/266, 12.8%) was about 95%, among which the proportion of VH4-34 (26/266, 9.8%), VH3-23 (25/266, 9.4%), VH3-7 (24/266, 9.0%), and VH4-39 (16/266, 6.0%) was about 35%. VH3-20 and VH3-49 only occurred in un-IgHV ( P <0.05). In addition, the expression rates of CD38 (26.3% vs. 3.0%), CD79b (71.1%∶45.5%) and 11q deletion (25.5%∶5.3%) were higher in un-IgHV, and single trisomy 12 (37.9%∶5.6%) were more commonly found in m-IgHV ( P <0.05). MYD88 was one of the major mutation genes in m-IgHV, while ATM had the highest mutation rate in un-IgHV. Conclusion: CLL patients have differential expression in terms of IgHV gene mutations, correlating to their immunophenotype and genetics characteristics.

Microplastics can act as carriers of heavy metals and may enter humans through ingestion and threaten human health. However, the bioaccessibility of heavy metals associated with microplastics and its implications for human health risk assessments are poorly understood. Therefore, in this study, four typical heavy metals (As(V), Cr(VI), Cd(II), and Pb(II)) and one typical microplastic (polyvinyl chloride, PVC) were chosen to estimate the human health risk of microplastic-associated heavy metals by incorporating bioaccessibility. Significant adsorption of heavy metals was observed with the following order for adsorption capacity: Pb(II) > Cr(VI) > Cd(II) > As(V); the efficiencies for desorption of these four heavy metals from PVC microplastics were all below 10%. The Fourier transform infrared spectroscopy results indicated that the functional groups on the surface of the virgin PVC microplastics did not play an important role in the capture process. Heavy metals in both gastric and small intestinal phases were prone to release from PVC microplastics when bioaccessibility was evaluated with the in vitro SBRC (Soluble Bioavailability Research Consortium) digestion model. In addition, Pb(II) bioaccessibility in the gastric phase was significantly higher than those in the other phases, while As(V), Cr(VI), and Cd(II) bioaccessibilities showed the opposite trend. After incorporating bioaccessibility adjustments, the noncarcinogenic hazards and carcinogenic risks determined were lower than those based on total metal contents. The individual hazard quotients (HQ) and carcinogenic risks (CR) for ingestion of these four heavy metals from PVC microplastics were all lower than the threshold values for adults and children. In summary, this study will provide a new view of the human health risks of heavy metals associated with microplastics., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

A novel virus named Aconitum amalgavirus 1 (AcoAV-1) was identified in Chinese aconite (Aconitum carmichaelii) plants. The complete genome of AcoAV-1 is 3,370 nucleotides long, containing two partially overlapping open reading frames encoding a putative coat protein and a RNA-dependent RNA polymerase, respectively. Its fusion protein shares 34.9%-50.7% amino acid sequence identity with other amalgaviruses. Phylogenetic analysis showed that this virus formed a clade with blueberry latent virus and four other related viruses, suggesting that it belongs to the genus Amalgavirus in the family Amalgaviridae., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Atropine is an anticholinergic drug widely used in the field of ophthalmology, but its abuse can cause cytotoxicity to the cornea, resulting in blurred vision. This study used cultured human corneal epithelial cells (HCECs) to investigate the mechanism of high-concentration atropine-induced cytotoxicity. HCECs were treated with different concentrations of atropine. The expression levels of microRNA (miR)-30c-1 and suppressor of cytokine signaling 3 (SOCS3) were manipulated in HCECs treated with 0.1% atropine. Cell counting kit-8 assay and flow cytometry were used to assess the viability and apoptosis of HCECs. The relationship between miR-30c-1 and SOCS3 was obtained from an online database and validated using a dual-luciferase reporter assay and RNA immunoprecipitation method. The effect of atropine on the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway was also investigated. High-concentration atropine inhibited the viability of HCECs and promoted their apoptosis. Moreover, atropine reduced miR-30c-1 expression and increased SOCS3 expression in a dose-dependent manner. It was found that miR-30c-1 targeted SOCS3. Overexpression of miR-30c-1-reduced atropine-induced HCEC cytotoxicity, whereas upregulation of SOCS3 reversed the effects of miR-30c-1 overexpression. High-concentration atropine inhibited activation of the JAK2/STAT3 signaling pathway via miR-30c-1/SOCS3. High-concentration atropine induces HCEC apoptosis by regulating the miR-30c-1/SOCS3 axis and JAK2/STAT3 signaling pathway., (© 2022 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.)

The biopharmaceutical market is driving the revolution from traditional batch processes to continuous manufacturing for higher productivity and lower costs. In this work, a batch mAb downstream process has been converted into an integrated continuous process with the combination of multiple techniques. For process intensification, two batch mode unit operations (protein A capture chromatography, ultrafiltration/diafiltration) were converted into continuous ones; for continuity, surge tanks were used between adjacent steps, and level signals were used to trigger process start or stop, forming a holistic continuous process. For process automation, manual operations (e.g., pH and conductivity adjustment) were changed into automatic operation and load mass was controlled with process analytical technology (PAT). A model-based simulation was applied to estimate the loading conditions for the continuous capture process, resulting in 21% resin capacity utilization and 28% productivity improvement as compared to the batch process. Automatic load mass control of cation exchange chromatography (CEX) was achieved through a customized in-line protein quantity monitoring system, with a difference of less than 1.3% as compared to off-line analysis. Total process time was shortened from 4 days (batch process) to less than 24 hours using the continuous downstream process with the overall productivity of 23.8 g mAb per day for the bench-scale system. Comparable yield and quality data were obtained in three test runs, indicating a successful conversion from a batch process to a continuous process. The insight of this work could be a reference to other similar situations., (© 2022 Wiley-VCH GmbH.)

Background: Allergic rhinitis (AR) is a highly prevalent chronic inflammatory disease of the respiratory tract. Previous studies have demonstrated that Bimin Kang Mixture (BMK) is effective in alleviating AR symptoms and reducing the secretion of inflammatory factors and mucin; however, the precise mechanisms underlying these effects remain unclear., Methods: We built target networks for each medication component using a network pharmacology technique and used RNA-seq transcriptome analysis to screen differentially expressed genes (DEGs) for AR patients and control groups. The overlapping targets in the two groups were assessed using PPI networks, GO, and KEGG enrichment analyses. The binding ability of essential components to dock with hub target genes was investigated using molecular docking. Finally, we demonstrate how BMK can treat AR by regulating the NF- κ B signaling pathway through animal experiments., Results: Effective targets from network pharmacology were combined with DEGs from RNA-seq, with 20 intersections as key target genes. The construction of the PPI network finally identified 5 hub target genes, and all hub target genes were in the NF- κ B signaling pathway. Molecular docking suggests that citric acid, deoxyandrographolide, quercetin, luteolin, and kaempferol are structurally stable and can spontaneously attach to IL-1 β , CXCL2, CXCL8, CCL20, and PTGS2 receptors. Animal experiments have shown that BMK inhibits NF- κ B transcription factor activation, reduces the expression of proinflammatory cytokines and chemokines IL-1 β , CXCL2, IL-8, and COX-2, and exerts anti-inflammatory and anti-allergic effects., Conclusion: BMK by regulating the NF- κ B signaling pathway improves inflammatory cell infiltration, regulates mucosal immune balance, and reduces airway hypersensitivity. These findings provide theoretical support for the clinical efficacy of BMK for AR treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li-Jie Qi et al.)

Sanggenon C is a flavonoid extracted from the root bark of white mulberry, which is a traditional Chinese medicine with anti-inflammatory, antioxidative, and antitumor pharmacological effects. In this study, sanggenon C was found to inhibit human gastric cancer (GC) cell proliferation and colony formation, induce GC cell cycle arrest in the G0-G1 phase, and promote GC cell apoptosis. Moreover, sanggenon C was found to decrease the level of mitochondrial membrane potential in GC cells and inhibit mitochondrial fission. Mechanistically, RNA sequencing, bioinformatics analysis, and a series of functional analyses confirmed that sanggenon C inhibited mitochondrial fission to induce apoptosis by blocking the extracellular regulated protein kinases (ERK) signaling pathway, and constitutive activation of ERK significantly abrogated these effects. Finally, sanggenon C was found to suppress the growth of tumor xenografts in nude mice without obvious side effects to the vital organs of animals. This study reveals that sanggenon C could be a novel therapeutic strategy for GC treatment.

Background: Isolated sulfite oxidase deficiency (ISOD) caused by sulfite oxidase gene (SUOX) mutations is a rare neurometabolic disease associated with ectopia lentis (EL). However, few genotype-phenotype correlations have been established yet., Methods: Potentially pathogenic SUOX mutations were screened from a Chinese cohort of congenital EL using panel-based next-generation sequencing and analyzed with multiple bioinformatics tools. The genotype-phenotype correlations were evaluated via a systematic review of SUOX mutations within our data and from the literature., Results: A novel paternal missense mutation, c.205G &gt; C (p.A69P), and a recurrent maternal nonsense mutation, c.1200 C &gt; G (p.Y400*), of SUOX were identified in a 4-year-old boy from 312 probands. The biochemical assays manifested elevated urine sulfite and S-sulfocysteine accompanied by decreased homocysteine in the blood. The patient had bilateral EL and normal fundus, yet minimal neurological involvement and normal brain structure. Molecular modeling simulation revealed the p.A69P mutant had an unstable structure but an unchanged affinity for sulfite, while the truncated p.Y400* mutant showed decreased binding capacity. Genotype-phenotype analysis demonstrated patients with biallelic missense mutations had milder symptoms (P = 0.023), later age of onset (P &lt; 0.001), and a higher incidence of regression (P = 0.017) than other genotypes. No correlations were found regarding EL and other neurological symptoms., Conclusion: The data from this study not only enrich the known mutation spectrum of SUOX but also suggest that missense mutations are associated with mild and atypical symptoms., (© 2022. The Author(s).)

Progestin therapy is the main fertility-sparing treatment for women with endometrial cancer (EC) and atypical endometrial hyperplasia (AEH). However, still 15-25% of these women failed to achieve complete response (CR) and then lost their fertility after definitive surgery. Metformin has been demonstrated to play an anti-cancer role in multiple cancers including EC. Several studies also suggested metformin had potential benefit in improving the therapeutic outcome of fertility-preserving treatment alongside with progestin. This review has discussed existed evidence regarding the effect of metformin combined with progestin for women with AEH and EC who desire childbearing. Nevertheless, the therapeutic effect of metformin varied in different studies due to the high heterogeneity in the patient's characteristics, the inconsistency in dose and treatment duration of metformin, the combined use of hysteroscopy, the insufficient sample size and underpowered study-design. Therefore, care should be taken when interpreting the current results on this issue. Till now, there is still no strong evidence supporting the use of metformin in fertility-preserving treatment in AEH and EEC patients. Further research is needed to provide high-quality data to validate the role of metformin as adjunctive therapy alongside with progestin to preserve fertility for AEH and EEC 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 Guan and Chen.)