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Hierarchical, ultrathin, and porous NiMoO 4 @CoMoO 4 on Co 3 O 4 hollow bones were successfully designed and synthesized by a hydrothermal route from the Co-precursor, followed by a KOH (potassium hydroxide) activation process. The hydrothermally synthesized Co 3 O 4 nanowires act as the scaffold for anchoring the NiMoO 4 @CoMoO 4 units but also show more compatibility with NiMoO 4 , leading to high conductivity in the heterojunction. The intriguing morphological features endow the hierarchical Co 3 O 4 @NiMoO 4 @CoMoO 4 better electrochemical performance where the capacity of the Co 3 O 4 @NiMoO 4 @CoMoO 4 heterojunction being 272 mA·h·g -1 at 1 A·g -1 can be achieved with a superior retention of 84.5% over 1000 cycles. The enhanced utilization of single/few NiMoO 4 @CoMoO 4 shell layers on the Co 3 O 4 core make it easy to accept extra electrons, enhancing the adsorption of OH - at the shell surface, which contribute to the high capacity. In our work, an asymmetric supercapacitor utilizing the optimized Co 3 O 4 @NiMoO 4 @CoMoO 4 activated carbon (AC) as electrode materials was assembled, namely, Co 3 O 4 @NiMoO 4 @CoMoO 4 //AC device, yielding a maximum high energy density of 53.9 W·h·kg -1 at 1000 W·kg -1 . It can retain 25.92 W·h·kg -1 even at 8100 W·kg -1 , revealing its potential and viability for applications. The good power densities are ascribed to the porous feature from the robust architecture with recreated abundant mesopores on the composite, which assure improved conductivity and enhanced diffusion of OH - and also the electron transport. The work demonstrated here holds great promise for synthesizing other heterojunction materials M 3 O 4 @MMoO 4 @MMoO 4 (M = Fe, Ni, Sn, etc).

Background: Almost all elderly patients with peritoneal metastatic gastric cancer (PGC) are unlikely to tolerate cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) and adjuvant chemotherapy. However, determining how to optimize the treatment strategy for such patients has always been a clinical problem. Both HIPEC and palliative adjuvant chemotherapy can benefit patients with PGC. Therefore, optimizing HIPEC and chemotherapy regimens has potential clinical value in reducing side effects, and improving treatment tolerance and clinical effectiveness., Aim: To explore the effect of HIPEC containing elemene, which is an anti-cancer component extracted in traditional Chinese herbal medicine, combined with reduced capecitabine and oxaliplatin (CapeOx) chemotherapy regimens, in elderly patients with PGC., Methods: In the present study, 39 of 52 elderly PGC patients were included and assigned to different HIPEC treatment groups [lobaplatin group (group L) and mixed group (group M)] for analysis. Lobaplatin was used for all three HIPECs in group L. In group M, lobaplatin was used in the middle of the three HIPECs, and elemene was used for the first and third HIPEC. After HIPEC, patients received CapeOx chemotherapy. The incidence of complications (abdominal infection, lung infection, and urinary tract infection), myelosuppression, immune function (CD4/CD8 ratio), average length of hospital stay, and prognosis were compared between these two groups., Results: There was no significant difference in the incidence of complications between the two groups during hospitalization ( P > 0.05). Compared to patients in group M, patients in group L exhibited severe myelosuppression ( P = 0.027) and increased length of hospital stay ( P = 0.045). However, no overall survival benefit was observed in group M. Furthermore, the immune function of patients in group M was less affected ( P < 0.001), when compared to that of patients in group L. The multivariate analysis suggested that the cycles of chemotherapy after perfusion significantly affected the prognosis of patients in both groups., Conclusion: Compared to the lobaplatin-based HIPEC regimen, the administration of elemene reduced the myelosuppression incidence in elderly PGC patients. The present study sheds light on the implementation of this therapeutic strategy for this set of patients., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Density functional calculations and microkinetic simulations were performed on the transformation network of acetylene on Pd(111), M(111) and PdM(111) (M = Cu, Ag, Au) surfaces. It is demonstrated that the adsorption energies on alloy surfaces linearly correlate with the values on the pure metal surfaces. A good linear relationship between the co-adsorption energies of initial states and transition states is revealed with which the barriers of most elementary steps in the reaction network were estimated. To shed light on the transformation of acetylene, microkinetic simulations were conducted on the network. The results show that CHCH and H are dominant species on the surfaces and CCH, CCH 2 and CCH 3 are the main intermediates. Analysis indicates that introduction of coinage metals into Pd reduces the activity, but promotes the selectivity by lowering the barrier of CHCH 2 → CH 2 CH 2 . The present work provides a comprehensive overview of acetylene transformation on palladium, coinage metals and their alloy surfaces. The linear relationship of adsorption energies between the component metal and alloy surfaces and usage of the TSS relationship to evaluate barriers for microkinetic simulations are worthy of being further studied and extended to other systems.

α-Amylase plays an important role in food processing and in-vivo digestion. Many biological functions of α-amylase are affected by unfolding. The pre-steady-state rapid unfolding kinetics of α-amylase remains unknown. In this study, the rapid unfolding kinetics of porcine pancreatic α-amylase (PPA) with guanidine hydrochloride (GdmHCl) were investigated by stopped-flow spectroscopy. Structural characterization of PPA by fluorescence spectroscopy, and molecular dynamics simulation showed that the unfolding process of PPA might start from the internal active center, where the β-sheet structure was destroyed, followed by the exposure of hydrophobic amino acid residues. Further research revealed that GdmHCl denaturized PPA not by complexing with PPA. The surrounding H-bond network of water was changed by GdmHCl. This research improves our understanding of the unfolding kinetics of the PPA on the microsecond scale. It also provides the evidence experimentally of the surrounding water contribution to protein denaturization., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: To observe the effect of moxibustion on skin lesions and immune inflammatory response in psoriasis mice, and to explore the possible mechanism of moxibustion for psoriasis., Methods: A total of 32 male BALB/c mice were randomly divided into a normal group, a model group, a moxibustion group and a medication group, 8 mice in each group. Psoriasis model was induced by applying 5% imiquimod cream on the back for 7 days in the model group, the moxibustion group and the medication group. At the same time of model establishment, the moxibustion group was treated with suspension moxibustion on skin lesions on the back, 20 min each time, once a day; the medication group was treated with 1 mg/kg methotrexate tablet solution by gavage, once a day. Both groups were intervened for 7 days. The daily changes of skin lesions were observed, and the psoriasis area and severity index (PASI) score was evaluated; the histopathological changes of skin lesions were observed by HE staining; the positive expression of proliferating cell nuclear antigen (PCNA) and T lymphocyte surface marker CD 3 were detected by immunohistochemistry; the expression level of serum interleukin (IL) -17A was detected by ELISA, and the relative expressions of tumor necrosis factor-α (TNF-α), IL-1β and IL-6 mRNA in skin lesions were detected by real-time PCR., Results: The increased and hypertrophy scale, dry skin, red and swollen epidermis and obvious infiltration were observed in the model group, and each score and total score of PASI were higher than those in the normal group ( P <0.01). The scale score, infiltration score, and total score of PASI in the moxibustion group were lower than those in the model group ( P <0.01); the infiltration score and total score of PASI in the medication group were lower than those in the model group ( P <0.01, P <0.05). The inflammatory cell infiltration in the model group was obvious, and the thickness of epidermal layer was increased compared with that in the normal group ( P <0.01); the inflammatory cell infiltration and Munro micro abscess were decreased in the moxibustion group and the medication group, and the thickness of epidermal layer was decreased compared with that in the model group ( P <0.01). Compared with the normal group, the positive cell number of PCNA and T was increased ( P <0.01), and the body mass was decreased, and the spleen index was increased ( P <0.01), and the expression of serum IL-17A and the relative expression of TNF-α, IL-1β and IL-6 mRNA in the skin lesions was increased in the model group ( P <0.01). Compared with the model group, the positive cell number of PCNA and T was reduced ( P <0.01), and the spleen index and the relative expression of TNF-α, IL-1β and IL-6 mRNA were reduced ( P <0.01) in the moxibustion group and the medication group; the body mass of mice in the moxibustion group was higher than that in the model group ( P <0.01); the content of serum IL-17A in the medication group was lower than that in the model group ( P <0.01); the relative expression of TNF-α, IL-1β mRNA in the moxibustion group was higher than that in the medication group ( P <0.01)., Conclusion: Moxibustion could effectively improve the scale and infiltration of skin lesions in psoriasis mice. Its mechanism may be related to inhibiting inflammatory response and regulating immunity.

G-quadruplexes in viral genomes can be applied as the targets of antiviral therapies, which has attracted wide interest. However, it is still not clear whether the pervasive number of such elements in the viral world is the result of natural selection for functionality. In this study, we identified putative quadruplex-forming sequences (PQSs) across the known viral genomes and analyzed the abundance, structural stability, and conservation of viral PQSs. A Viral Putative G-quadruplex Database (http://jsjds.hzau.edu.cn/MBPC/ViPGD/index.php/home/index) was constructed to collect the details of each viral PQS, which provides guidance for selecting the desirable PQS. The PQS with two putative G-tetrads (G 2 -PQS) was significantly enriched in both eukaryotic viruses and prokaryotic viruses, whereas the PQSs with three putative G-tetrads (G 3 -PQS) were only enriched in eukaryotic viruses and depleted in prokaryotic viruses. The structural stability of PQSs in prokaryotic viruses was significantly lower than that in eukaryotic viruses. Conservation analysis showed that the G 2 -PQS, instead of G 3 -PQS, was highly conserved within the genus. This suggested that the G 2 -quadruplex might play an important role in viral biology, and the difference in the occurrence of G-quadruplex between eukaryotic viruses and prokaryotic viruses may result from the different selection pressures from hosts., Competing Interests: Conflict of interest The authors declare no competing interests., (Copyright © 2021 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. All rights reserved.)

Lithium-sulfur (Li-S) battery is identified as one of the most promising next-generation energy storage systems due to its ultra-high theoretical energy density up to 2600 Wh kg -1 . However, Li metal anode suffers from dramatic volume change during cycling, continuous corrosion by polysulfide electrolyte, and dendrite formation, rendering limited cycling lifespan. Considering Li metal anode as a double-edged sword that contributes to ultrahigh energy density as well as limited cycling lifespan, it is necessary to evaluate Li-based alloy as anode materials to substitute Li metal for high-performance Li-S batteries. In this contribution, the authors systematically evaluate the potential and feasibility of using Li metal or Li-based alloys to construct Li-S batteries with an actual energy density of 500 Wh kg -1 . A quantitative analysis method is proposed by evaluating the required amount of electrolyte for a targeted energy density. Based on a three-level (ideal material level, practical electrode level, and pouch cell level) analysis, highly lithiated lithium-magnesium (Li-Mg) alloy is capable to achieve 500 Wh kg -1 Li-S batteries besides Li metal. Accordingly, research on Li-Mg and other Li-based alloys are reviewed to inspire a promising pathway to realize high-energy-density and long-cycling Li-S batteries., (© 2021 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Abstract: Reconstruction of peripheral nerve injury remains a challenge for clinical medicine. Previous reports have confirmed that external oblique muscle-fabricated nerve conduit (EMC) could effectively be used to promote peripheral nerve regeneration. In this study, we compared between conduits fabricated from fresh muscle and conduits fabricated from predegenerated muscle for the repair of peripheral nerve defects in a mouse sciatic nerve transection model. We found that the number, diameter, and myelin sheath thickness of the myelinated nerve fibers of the regenerative nerve in the EMC group were larger than those of the predegenerated-EMC (P-EMC) group eight weeks after surgery. The sciatic function index and gastrocnemius wet-weight mass ratio in the EMC group were higher than those in the P-EMC group. The Bcl-2/Bax ratio and the number of Schwann cell nucleus in the proximal nerve stumps in the EMC group were greater than those in the P-EMC group. In conclusion, our results confirmed that the use of fresh skeletal muscle nerve conduit increased the Bcl-2/Bax ratio and promoted the survival of Schwann cells of the proximal nerve stump compared with that of predegenerated skeletal muscle nerve conduits, thus achieving better functional recovery after sciatic nerve defect., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by Mutaz B. Habal, MD.)

Background: Previous nomograms for hepatocellular carcinoma (HCC) did not include the neutrophil-to-lymphocyte ratio (NLR) or platelet-to-lymphocyte ratio (PLR). This study aimed to establish an effective nomogram capable of estimating the association between preoperative inflammatory factors and overall survival (OS) of HCC patients after hepatectomy., Aim: To analyse the factors affecting the prognosis of HCC and establish a nomogram., Methods: A total of 626 HCC patients (410 training set patients from the First Affiliated Hospital of Anhui Medical University and 216 validation set patients from the First Affiliated Hospital of University of Science and Technology of China) underwent hepatectomy from January 2014 to December 2017 and were followed up every 3-6 mo. The nomogram was based on OS-related independent risk factors identified by Cox regression analysis. The C-index, calibration curve, and area under the curve (AUC) were used to evaluate the nomogram's accuracy., Results: The 1-, 2- and 3-year OS rates were 79.0%, 68.0% and 45.4% in the training cohort (median OS = 34 mo) and 92.1%, 73.9% and 51.2% in the validation cohort (median OS = 38 mo). Higher α-fetoprotein [hazard ratio (HR) = 1.812, 95% confidence interval (CI): 1.343-2.444], NLR (HR = 2.480, 95%CI: 1.856-3.312) and PLR (HR = 1.974, 95%CI: 1.490-2.616), tumour size ≥ 5 cm (HR = 1.323, 95%CI: 1.002-1.747), and poor differentiation (HR = 3.207, 95%CI: 1.944-5.290) were significantly associated with shortened OS. The developed nomogram integrating these variables showed good reliability in both the training (C-index = 0.71) and validation cohorts (C-index = 0.75). For predicting 1-, 2- and 3-year OS, the nomogram had AUCs of 0.781, 0.743 and 0.706 in the training cohort and 0.789, 0.815 and 0.813 in the validation cohort. The nomogram was more accurate in predicting prognosis than the AJCC TNM staging system., Conclusion: The prognostic nomogram combining pathological characteristics and inflammation indicators could provide a more accurate individualized risk estimate for the OS of HCC patients with hepatectomy., Competing Interests: Conflict-of-interest statement: The authors declare that there are no any conflicts of interest., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Aims: To investigate the lens biometric parameters in congenital lens deformities, using a novel technique of swept-source anterior segment optical coherence tomography (SS-ASOCT). Methods: This prospective study included patients with microspherophakia (MSP), coloboma lentis (CL), and posterior lenticonus (PL). For this cohort, 360-degree high-resolution lens images were obtained using the latest SS-ASOCT (CASIA2, Tomey Corp, Nagoya, Japan). The lens biometric parameters were calculated by the CASIA2 built-in software for anterior lens radius (ALR), posterior lens radius (PLR), anteroposterior distance (APD), anterior chamber depth (ACD), equatorial diameter (Eq Dia), rear projection length (RPL), and maximum diameter of the lesion (MDL). Results: This study included two eyes each with MSP and CL and one eye with PL. The lens of MSP was spherical and posteriorly dislocated, with decreased ALR and PLR, Eq Dia, but increased APD. In patients with CL, the coloboma was isolated, bilateral, inferior, and located toward the maldeveloped ciliary body. High astigmatism was mainly lenticular, and this was calculated by the ALR and PLR. Regarding the site of coloboma, a significant decrease in ALR was observed, while the PLR and APD were not affected. The PL eyes had a cone-shaped protrusion of the posterior lens surface with a subtle cataractous region around the apex. An extremely high posterior surface curvature was observed with a mean PLR of 1.67 mm. The RPL and MDL were about 1.80 and 0.4 mm, respectively, which were homogenous at different sections. Conclusions: The CASIA2 is a valuable option for in vivo crystalline lens measurement for congenital lens deformities, enabling the accurate diagnosis and providing illuminating insights into the pathogenesis of MSP, CL, and PL., 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 © 2021 Chen, Jia and Jiang.)

Background: Colorectal cancer (CRC) represents the third most common malignant tumor in the worldwide. Radiotherapy is the common therapeutic treatment for CRC, but radiation resistance is often encountered. ChIP-seq of Histone H3K27 acetylation (H3K27ac) has revealed enhancers that play an important role in CRC. This study examined the relationship between an active CRC enhancer and claudin-1 (CLDN1), and its effect on CRC radiation resistance., Methods: The target CRC genes of active enhancers were obtained from public H3K27ac ChIP-seq, and the genes highly expressed in radio-resistant CRC were screened and intersected with enhancer-driven genes. The clinical roles of CLDN1 in radiation resistance were examined using the t-test, standard mean deviation (SMD), summary receiver operating characteristic curve and Kaplan-Meier curves. The co-expressed genes of CLDN1 were calculated using Pearson Correlation analysis, and Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes and Gene Set Variation Analysis (GSVA) analyses were used to examine the molecular mechanisms of CLDN1., Results: Total 13 703 CRC genes were regulated by enhancers using 58 H3K27ac ChIP-seq. Claudin-1 (CLDN1) was enhancer-driven and notably up-regulated in CRC tissues compared to non-CRC controls, with a SMD of 3.45 (95 CI % = .56-4.35). CLDN1 expression was increased in radiation-resistant CRC with a SMD of .42 (95% CI = .16-.68) and an area under the curve of .74 (95% CI = .70-.77). The cell cycle and immune macrophage levels were the most significant pathways associated with CLDN1., Conclusion: CLDN1 as an enhancer-regulated gene that can boost radiation resistance in patients with CRC., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Background: Post-extubation cough is a common phenomenon in surgical patients undergoing general anesthesia, which can lead to potentially dangerous complications. In this meta-analysis, we evaluated the efficacy and safety of intracuff alkalinized lidocaine in patients with tracheal intubation to prevent cough and other airway complications during the perioperative period., Aim: To perform a systematic review and meta-analysis of intracuff alkalinized lidocaine for the prevention of postoperative airway complications., Methods: PubMed, Embase, Cochrane, and Web of Science were searched for randomized controlled trials (RCTs) that compared intracuff alkalinized lidocaine to placebo. We used risk-of-bias assessment to assess the RCTs, and the quality of evidence was assessed using the grading of recommendations, assessment, development, and evaluations., Results: Twelve randomized trials (1175 patients) were analyzed. Meta-analysis showed that intracuff alkalinized lidocaine was associated with less cough compared to that produced by placebo [risk ratio (RR): 0.38; 95% confidence interval (CI): 0.23-0.63]. Similarly, intracuff alkalinized lidocaine was more effective than the control in reducing postoperative sore throat at 24 h (RR: 0.19; 95%CI: 0.09-0.41) and postoperative hoarseness (RR: 0.38; 95%CI: 0.21-0.69)., Conclusion: Intracuff alkalinized lidocaine is an effective adjuvant that can decrease airway complications, such as coughing, hoarseness, and sore throat., Competing Interests: Conflict-of-interest statement: The authors report no conflict of interest., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Scaling relations play a vital role in high-throughput screening of catalytic materials, and more and more attention is being paid to strain-based regulation of catalytic performance. Here we investigated the variation of several energetics, including adsorption energies in the initial state, transition state, and final state, reaction energies, and energy barriers with strain, by studying CO, BH, NH, CH, and NO adsorption and dissociation on M(111) (M = Cu, Ag, Ni, Pd, or Pt) surfaces. We show that energy barriers, reaction energies, and adsorption energies can vary either linearly or nonlinearly (quadratically) with strain. Systems with stronger adsorbate-substrate interaction and weaker atom-atom interaction in substrates are more likely to exhibit nonlinear relations. The well-known Brønsted-Evans-Polanyi relationships and transition state scaling relationships under strain were also examined, and both of them can be nonlinear under strain, in principle. The observed nonlinear relationships were satisfactorily rationalized with the equations derived from Mechanics of Solids.

To provide guiding information for developing efficient and stable catalysts for epoxide hydration, we investigated the mechanism of propylene oxide (PO) to 1,2-propylene glycol (PG) using density functional theory (DFT) calculations. The mechanism was identified to follow the cooperative bimetallic mechanism in which a metal-salen complex activated H 2 O attacks the middle carbon atom of a metal-salen complex activated PO from the oxygen side of three-membered ring. Analyses reveal that the distortion energy correlates linearly with the barrier, and the hydrogen bonding between H 2 O and PO increases from reaction precursors to transition states. A nice linear relationship exists between the ratio of square root of ionic potential to the square of the distance from the metal ion spherical surface to the oxygen atom center of PO. It is demonstrated that the substrates with larger polarizability tend to have lower hydration barriers and the influence of ligands is less than that of metal centers and substrates. Modifying metal ions is the first choice for developing metal-salen catalysts, and metal ions with more formal charges and larger radius are expected to exhibit high activity. These findings shed lights on the mechanism and provide guiding information for developing efficient metal-salen catalysts for epoxide hydration.

The origination of new genes contributes to the biological diversity of life. New genes may quickly build their network, exert important functions, and generate novel phenotypes. Dating gene age and inferring the origination mechanisms of new genes, like primate-specific genes, is the basis for the functional study of the genes. However, no comprehensive resource of gene age estimates across species is available. Here, we systematically date the age of 9,102,113 protein-coding genes from 565 species in the Ensembl and Ensembl Genomes databases, including 82 bacteria, 57 protists, 134 fungi, 58 plants, 56 metazoa, and 178 vertebrates, using a protein-family-based pipeline with Wagner parsimony algorithm. We also collect gene age estimate data from other studies and uniformly distribute the gene age estimates to time ranges in a million years for comparison across studies. All the data are cataloged into GenOrigin (http://genorigin.chenzxlab.cn/), a user-friendly new database of gene age estimates, where users can browse gene age estimates by species, age, and gene ontology. In GenOrigin, the information such as gene age estimates, annotation, gene ontology, ortholog, and paralog, as well as detailed gene presence/absence views for gene age inference based on the species tree with evolutionary timescale, is provided to researchers for exploring gene functions., (Copyright © 2021 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Ltd. All rights reserved.)

With the increasing awareness of men's health, more and more clinical studies are reported on the relationship of testicular microlithiasis (TM) with male infertility. TM is a relatively rare disease characterized by multiple microcalcifications (<3 mm) in the seminiferous tubules of the testis. This review summarizes the findings in the studies of the diagnosis, epidemiology, correlation with male fertility, treatment, and follow-up of TM in recent years. Many researches show that TM has a certain correlation with the decline of male fertility, which, however, is not identically agreed on at home and abroad. As for the treatment of TM complicated with male infertility, there is still a lack of effective and reliable drugs and strategies and a need for many basic and clinical studies.

Lithium-sulfur (Li-S) batteries constitute promising next-generation energy storage devices due to the ultrahigh theoretical energy density of 2600 Wh kg -1 . However, the multiphase sulfur redox reactions with sophisticated homogeneous and heterogeneous electrochemical processes are sluggish in kinetics, thus requiring targeted and high-efficient electrocatalysts. Herein, a semi-immobilized molecular electrocatalyst is designed to tailor the characters of the sulfur redox reactions in working Li-S batteries. Specifically, porphyrin active sites are covalently grafted onto conductive and flexible polypyrrole linkers on graphene current collectors. The electrocatalyst with the semi-immobilized active sites exhibits homogeneous and heterogeneous functions simultaneously, performing enhanced redox kinetics and a regulated phase transition mode. The efficiency of the semi-immobilizing strategy is further verified in practical Li-S batteries that realize superior rate performances and long lifespan as well as a 343 Wh kg -1 high-energy-density Li-S pouch cell. This contribution not only proposes an efficient semi-immobilizing electrocatalyst design strategy to promote the Li-S battery performances but also inspires electrocatalyst development facing analogous multiphase electrochemical energy processes.

Mutations of fibrillin-1 (FBN1) have been associated with Marfan syndrome and pleiotropic connective tissue disorders, collectively termed as "type I fibrillinopathy". However, few genotype-phenotype correlations are known in the ocular system. Patients with congenital ectopia lentis (EL) received panel-based next-generation sequencing, complemented with multiplex ligation-dependent probe amplification. In a total of 125 probands, the ocular phenotypes were compared for different types of FBN1 mutations. Premature termination codons were associated with less severe EL and a thinner central corneal thickness (CCT) than the inframe mutations. The eyes of patients with mutations in the C-terminal region had a higher incidence of posterior staphyloma than those in the middle and N-terminal regions. Mutations in the TGF-β-regulating sequence had larger horizontal corneal diameters (white-to-white [WTW]), higher incidence of posterior staphyloma, but less severe EL than those with mutations in other regions. Mutations in the neonatal region were associated with thinner CCT. Longer axial length (AL) was associated with mutations in the C-terminal region or TGF-β regulating sequence after adjusting for age, EL severity, and corneal curvature radius. FBN1 genotype-phenotype correlations were established for some ocular features, including EL severity, AL, WTW, CCT, and so forth, providing novel perspectives and directions for further mechanistic studies., (© 2021 Wiley Periodicals LLC.)

Lespedezadanxiaensis (Fabaceae), a new species from Danxiashan National Nature Reserve in Guangdong Province, is described and illustrated. The new species is morphologically similar to Lespedezapilosa , but it can be easily distinguished by its thin leathery leaflets and long peduncles. Phylogenetic analysis based on ITS confirmed that the new species belongs to Lespedezasubg.Macrolespedeza. The new species is the first known species of Lespedeza endemic to Danxia landform and is currently only known from Mount Danxia, Guangdong., (Wan-Yi Zhao, Kai-Wen Jiang, Zai-Xiong Chen , Bin Tian, Qiang Fan.)

Pig cloning by somatic cell nuclear transfer (SCNT) frequently undergoes incomplete epigenetic remodeling during the maternal-to-zygotic transition, which leads to a significant embryonic loss before implantation. Here, we generated the first genome-wide landscapes of histone methylation in pig SCNT embryos. Excessive H3K9me3 and H3K27me3, but not H3K4me3, were observed in the genomic regions with unfaithful embryonic genome activation and donor-cell-specific gene silencing. A combination of H3K9 demethylase KDM4A and GSK126, an inhibitor of H3K27me3 writer, were able to remove these epigenetic barriers and restore the global transcriptome in SCNT embryos. More importantly, thymine DNA glycosylase (TDG) was defined as a pig-specific epigenetic regulator for nuclear reprogramming, which was not reactivated by H3K9me3 and H3K27me3 removal. Both combined treatment and transient TDG overexpression promoted DNA demethylation and enhanced the blastocyst-forming rates of SCNT embryos, thus offering valuable methods to increase the cloning efficiency of genome-edited pigs for agricultural and biomedical purposes., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Neuroblastoma is the commonest extracranial pediatric malignancy. With few recurrent single nucleotide variations (SNVs), mutation-based precision oncology approaches have limited utility, but its frequent and heterogenous copy number variations (CNVs) could represent genomic dependencies that may be exploited for personalized therapy. Patient-derived cell culture (PDC) models can facilitate rapid testing of multiple agents to determine such individualized drug-responses. Thus, to study the relationship between individual genomic aberrations and therapeutic susceptibilities, we integrated comprehensive genomic profiling of neuroblastoma tumors with drug screening of corresponding PDCs against 418 targeted inhibitors. We quantified the strength of association between copy number and cytotoxicity, and validated significantly correlated gene-drug pairs in public data and using machine learning models. Somatic mutations were infrequent (3.1 per case), but copy number losses in 1p (31%) and 11q (38%), and gains in 17q (69%) were prevalent. Critically, in-vitro cytotoxicity significantly correlated only with CNVs, but not SNVs. Among 1278 significantly correlated gene-drug pairs, copy number of GNA13 and DNA damage response genes CBL, DNMT3A, and PPM1D were most significantly correlated with cytotoxicity; the drugs most commonly associated with these genes were PI3K/mTOR inhibitor PIK-75, and CDK inhibitors P276-00, SNS-032, AT7519, flavopiridol and dinaciclib. Predictive Markov random field models constructed from CNVs alone recapitulated the true z-score-weighted associations, with the strongest gene-drug functional interactions in subnetworks involving PI3K and JAK-STAT pathways. Together, our data defined individualized dose-dependent relationships between copy number gains of PI3K and STAT family genes particularly on 17q and susceptibility to PI3K and cell cycle agents in neuroblastoma. Integration of genomic profiling and drug screening of patient-derived models of neuroblastoma can quantitatively define copy number-dependent sensitivities to targeted inhibitors, which can guide personalized therapy for such mutationally quiet cancers., 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 © 2021 Wong, Wong, Kuick, Saffari, Wong, Tan, Merchant, Chang, Thangavelu, Periyasamy, Chen, Iyer, Tan, Soh, Iyer, Fan and Loh.)

Intraneuronal neurofibrillary tangles composed of Tau aggregates have been widely accepted as an important pathological hallmark of Alzheimer's disease. A current therapeutic avenue for treating Alzheimer's disease is aimed at inhibiting Tau accumulation with small molecules such as natural flavonoids. Liquid-liquid phase separation (LLPS) of Tau can lead to its aggregation, and Tau aggregates can then be degraded by autophagy. However, it is unclear whether natural flavonoids modulate the formation of phase-separated Tau droplets or promote autophagy and Tau clearance. Here, using confocal microscopy and fluorescence recovery after photobleaching assays, we report that a natural antioxidant flavonoid compound myricetin slows LLPS of full-length human Tau, shifting the equilibrium phase boundary to a higher protein concentration. This natural flavonoid also significantly inhibits pathological phosphorylation and abnormal aggregation of Tau in neuronal cells and blocks mitochondrial damage and apoptosis induced by Tau aggregation. Importantly, using coimmunoprecipitation and Western blotting, we show that treatment of cells with myricetin stabilizes the interaction between Tau and autophagy-related protein 5 (ATG5) to promote clearance of phosphorylated Tau to indirectly limit its aggregation. Consistently, this natural flavonoid inhibits mTOR pathway, activates ATG5-dependent Tau autophagy, and almost completely suppresses Tau toxicity in neuronal cells. Collectively, these results demonstrate how LLPS and abnormal aggregation of Tau are inhibited by natural flavonoids, bridging the gap between Tau LLPS and aggregation in neuronal cells, and also establish that myricetin could act as an ATG5-dependent autophagic activator to ameliorate the pathogenesis of Alzheimer's disease., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Previous studies have shown that increased neutrophils, as a manifestation of oxidative stress, may be involved in the progression of kidney disease. To our knowledge, little is known about the relationship between neutrophils and renal impairment in rheumatoid arthritis (RA). Therefore, we aim to investigate whether neutrophil is associated with renal impairment in RA patients., Methods: We retrospectively investigated the renal function of 602 RA patients in the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine by estimated glomerular filtration rate (eGFR) from September 2018 and September 2019. The exposure variable was neutrophils, and the main outcome was eGFR. General data (gender, age, duration, hypertension, diabetes, hobbies, and medication history), whole blood markers, lipid indexes, and inflammatory indexes were collected as much as possible. We used multivariable logistic regression analysis to evaluate the association between neutrophils and renal impairment in RA participants., Results: A total of 89 cases (14.8%) had renal impairment with eGFR < 60 ml/min/1.73 m 2 , and 75 cases (84.3%) were female. Subgroup analysis showed that female (odds ratio [OR] = 0.523, 95% confidence interval [CI]: 0.318-0.867, p = .011), neutrophils greater thsn 7.5 × 10 9 /L (OR = 2.314, 95% CI: 1.310-4.087, p = .004), NLR > 3.53 (OR = 1.757, 95% CI: 1.104-2.799, p = .018), hemoglobin less than 120 g/L (OR = 2.413, 95% CI: 1.418-4.118, p = .001), and UA > 360 μmol/L (OR = 6.052, 95% CI: 3.708-9.878, p < .001) was related to renal damage in RA. Adjusted for several confounders, the multivariable analysis indicated that neutrophils greater than 7.5 × 10 9 /L (OR = 1.784, 95% CI: 1.164-3.288, p = .031) was independently associated with an increased risk of renal impairment in RA., Conclusion: Our study demonstrated that neutrophils greater than 7.5 × 10 9 /L was associated with a high risk of renal impairment in RA, suggesting that neutrophil may be a biomarker for renal impairment in RA., (© 2021 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

Background: Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers in the world, the detection and prognosis of which are still unsatisfactory. Thus, it is essential to explore the factors that may identify ESCC and evaluate the prognosis of ESCC patients., Results: Both protein and mRNA expression levels of BIRC5 are upregulated in ESCC group rather than non-ESCC group (standardized mean difference > 0). BIRC5 mRNA expression is related to the age, tumor location, lymph node stage and clinical stage of ESCC patients (p < 0.05). BIRC5 expression makes it feasible to distinguish ESCC from non-ESCC (area under the curve > 0.9), and its high expression is related to poor prognosis of ESCC patients (restrictive survival time difference = -0.036, p < 0.05). BIRC5 may play an important role in ESCC by influencing the cell cycle pathway, and CDK1, MAD2L and CDC20 may be the hub genes of this pathway. The transcription factors-MAZ and TFPD1 -are likely to regulate the transcription of BIRC5, which may be one of the factors for the high expression of BIRC5 in ESCC., Conclusions: The current study shows that upregulation of BIRC5 may have essential clinical value in ESCC, and contributes to the understanding of the pathogenesis of ESCC.

Abstract: Rhabdomyosarcoma is the most common soft tissue sarcoma in children, and embryonal rhabdomyosarcoma is the most typical type of rhabdomyosarcoma. The heterogeneity, etiology, and origin of embryonal rhabdomyosarcoma remain unknown.After obtaining the gene expression data of every cell in the tumor tissue by single-cell RNA sequencing, we used the Seurat package in R studio for quality control, analysis, and exploration of the data. All cells are divided into tumor cells and non-tumor cells, and we chose tumor cells by marker genes. Then, we repeated the process to cluster the tumor cells and divided the subgroups by their differentially expressed genes and gene ontology/Kyoto Encyclopedia of Genes and Genomes analysis. Additionally, Monocle 2 was used for pseudo-time analysis to obtain the evolution trajectory of cells in tumor tissues.Tumor cells were divided into 5 subgroups according to their functions, which were characterized by high proliferation, sensing and adaptation to oxygen availability, enhanced epigenetic modification, enhanced nucleoside phosphonic acid metabolism, and ossification. Evolution trajectory of cells in tumor tissues is obtained.We used pseudo-time analysis to distinguish between mesenchymal stem cells and fibroblasts, proved that embryonal rhabdomyosarcoma in the pelvic originated from skeletal muscle progenitor cells, showed the evolutionary trajectory of embryonal rhabdomyosarcoma, and improved the method of evaluating the degree of malignancy of embryonal rhabdomyosarcoma., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To observe the short-term and long-term effects of moxibustion on plaque psoriasis of blood stasis, and to compare the curative effect between moxibustion and calcipotriol ointment., Methods: A total of 80 patients with plaque psoriasis of blood stasis were randomly divided into an observation group (40 cases, 2 cases dropped off) and a control group (40 cases, 4 cases dropped off). Both groups were given routine medical vaseline topical emollient basic treatment. In the observation group, moxibustion was applied to ashi point (target skin lesions), Zusanli (ST 36), Xuehai (SP 10) and Qihai (CV 6) for 30 min each time, 3 times a week. The control group was treated with calcipotriol ointment (0.25 g each time, once in the morning and evening) on the target skin lesions. Both groups were treated for 8 weeks. The psoriasis area and severity index (PASI) score before and after treatment, main clinical symptoms of TCM score and dermatology life quality index (DLQI) score before and after treatment and 3 and 6 moths follow-up were observed in the two groups; the clinical efficacy after treatment was evaluated and the recurrence rates of the two groups were followed up for 3 and 6 months after treatment., Results: After treatment, the PASI scores in the both groups were lower than before treatment ( P <0.01). After treatment and 3 and 6 months follow-up, the main clinical symptoms of TCM scores and DLQI scores of the two groups were lower than those before treatment ( P <0.05), and at 3 and 6 months follow-up, those in the observation group were lower than the control group ( P <0.01). There was no statistically significant difference between the observation group and the control group in overall effective rate and target skin lesion effective rate ( P >0.05). At 3 and 6 months follow-up, the overall recurrence rate and target skin lesion recurrence rate in the observation group were lower than those in the control group ( P <0.05)., Conclusion: Both moxibustion and calcipotriol ointment have good short-term effects on plaque psoriasis of blood stasis. Moxibustion has more advantages in reducing the recurrence rate of psoriasis, improving the main clinical symptoms of TCM and quality of life.

Objective: To study the prevalence and genetic characteristics of human respiratory syncytial virus (HRSV) in Quanzhou city, from 2018 to 2019. Methods: A total of 141 throat swabs were collected from children patients of lower respiratory tract infection in Quanzhou children Hospital, Fujian Province from November 2018 to May 2019. RT-PCR was used to amplify the 3 'end of G gene HRSV. Sequencer 5.0 and MEGA5.05 softwares were used for sequence editing, phylogenetic tree construction and genotyping analysis. Results: Twenty-five samples were positive for HRSV. Seventeen samples succeeded to obtain the target gene, including 13 of HRSVA and 4 of HRSVB. Two genotypes were identified: ON1 genotype (13 samples, HRSVA) and BA9 genotype (4 samples, HRSVB). Five strains of ON1 genotype sequences were clustered with the ON1 sequences prevalent in Beijing, Changchun and Zhejiang from 2012 to 2015 (cluster1); one strain (FJ19-02) was clustered with the sequences of ON1 genotype circulating in many regions of China from 2012 to 2015 (cluster2); Seven strains were clustered independently (cluster FJ). FJ18-02, FJ19-14 and FJ19-15 of HRSVB were clustered with the BA9 genotype sequences prevalent in Changchun, Jilin Province in 2015, while FJ19-13 was closely related to the BA9 genotype sequences prevalent in Guangzhou and Zhejiang Province in 2013. Both the ON1 and BA9 genotypes showed variations of nucleotide and amino acid in 72 and 60 insertion segments. Amino acid mutation (H266L) only occurred among the sequence of cluster-FJ, and the mutations of H261Q and Q265L only appeared in strain FJ19-13. Conclusion: BA9 and ON1 genotypes were prevalent in Quanzhou city, from 2018 to 2019. Cluster-FJ was a newly discovered independent transmission chain, which may continue to circulate in local Quanzhou area.

Magmatism has profoundly influenced the evolution of the geosphere, hydrosphere, atmosphere, and biosphere in back-arc basins. However, the timing of the magmatism in the Okinawa Trough (OT) is not well constrained by the age spectra of zircons. Here, for the first time, we carry out an integrated study combining in situ analysis of zircon U-Th-Pb and Hf-O isotopes, and trace element compositions of zircons from the volcanic rocks from the southernmost part of the OT. We found that the young (< 100 ka) zircons in these volcanic rocks have old (108 Ma to 2.7 Ga) inherited cores, which were captured as the magma ascended through the rifting continental crust. In particular, the inherited Archean zircons strongly suggest that remnants of the old East Asian continental blocks underlie the embryonic crustal rifting zone. Moreover, the ages of most of the inherited zircons correspond to five supercontinent amalgamation events. Specifically, the Archaean inherited zircons, which have positive εHf (t) and low δ 18 O values, correspond to the formation of juvenile continental crust. In contrast, the negative εHf (t) and high δ 18 O values of the post-Archaean inherited zircons indicate that their parental magma contained recycled older crust due to the enhanced crust-mantle interactions during the evolution of the early continental crust. Therefore, the inherited zircons in the back-arc volcanic rocks not only reflect the evolution of the local magmatism, but they also contain a record of the Archaean crustal fragment and of several global continental amalgamation events.

Objective: To study the application of cell transfer technology to solve the problem of the limited number of fine needle aspiration cytology (FNAC) smears for various immunocytochemistry (ICC) staining and other auxiliary tests, and to enhance accurate cytological diagnosis. Methods: Thirty-four cases of FNAC smears from January 2020 to April 2020 in the Department of Pathology of Beijing Hospital were collected for investigation of the cell transfer technique. The materials in the most cell smear were divided and transferred to several glass slides. After de-staining, the recipient slides were stained with EnVision ICC. The technique was validated by comparing the consistency of the ICC of transferred cell smears and the corresponding immunohistochemical (IHC) staining on biopsies. Results: There were a total of 180 cell transfer slides from 34 cases, of which 174 had the same cell morphology, size and structure as the original smears, with the success rate of cell transfer of 96.7% (174/180). Totally 174 ICC stains were performed on the successfully transferred cell smears, of which 153 smears had available corresponding IHC staining of histologic specimens. Of these, 148 showed concordance between ICC staining and the IHC staining. Cells were successfully transferred in 96.7 % (148/153) of the cell sheets, keeping the same morphology and structure as compared to their original smears. The diagnosis of all 34 FNAC cases was the same to that of their corresponding pathology on biopsies with 100 % concordance. Conclusions: The cell transfer technique is a simple and effective way to make full use of diagnostic cells on a cell smear, and is valuable for accurate cytological diagnosis.

Aging is one of the most prominent risk factors for heart failure. Myeloid-derived suppressor cells (MDSCs) accumulate in aged tissue and have been confirmed to be associated with various aging-related diseases. However, the role of MDSCs in the aging heart remains unknown. Through RNA-seq and biochemical approaches, we found that granulocytic MDSCs (G-MDSCs) accumulated significantly in the aging heart compared with monocytic MDSCs (M-MDSCs). Therefore, we explored the effects of G-MDSCs on the aging heart. We found that the adoptive transfer of G-MDSCs of aging mice to young hearts resulted in cardiac diastolic dysfunction by inducing cardiac fibrosis, similar to that in aging hearts. S100A8/A9 derived from G-MDSCs induced inflammatory phenotypes and increased the osteopontin (OPN) level in fibroblasts. The upregulation of fibroblast growth factor 2 (FGF2) expression in fibroblasts mediated by G-MDSCs promoted antisenescence and antiapoptotic phenotypes of fibroblasts. SOX9 is the downstream gene of FGF2 and is required for FGF2-mediated and G-MDSC-mediated profibrotic effects. Interestingly, both FGF2 levels and SOX9 levels were upregulated in fibroblasts but not in G-MDSCs and were independent of S100A8/9. Therefore, a novel FGF2-SOX9 signaling axis that regulates fibroblast self-renewal and antiapoptotic phenotypes was identified. Our study revealed the mechanism by which G-MDSCs promote cardiac fibrosis via the secretion of S100A8/A9 and the regulation of FGF2-SOX9 signaling in fibroblasts during aging.

Objective: To investigate whether Hydrolyzed Seawater Pearl tablet (HSPT) could modulate the Th1/Th2 imbalance in an immunosuppressed mouse model with Th1 to Th2 shift induced by Cyclosporine A (CsA) which can be used in the clinical treatment of Th2 to Th1 shift diseases, and explore the possible mechanism for the adjuvant therapeutic efficacy of HSPT on recurrent respiratory infections (RRI) and acquired immune deficiency syndrome (AIDS)., Methods: The mice were randomly divided into six groups of five animals each, namely normal group, model group, lentinan polysaccharide tablet (LPT) group and three HPST treated groups. HPST treated groups were administered with HPST (0.51, 1.02, 2.04 g/kg) via intragastric gavage (i.g) for 30 consecutive days. LPT used as reference drug for positive control, LPT group was administered with LPT (8.2 mg/kg) for 30 consecutive days. Normal group and model group were received distilled water. The animals in model group, LPT group and HPST treated groups were injected intraperitoneally with CsA (50 mg/kg) to establish the immunosuppressed mice model with Th1 to Th2 shift on the 20th, 22nd and 24th day, one hour after the administration of the respective treatment. Animals were sacrificed one hour after the last administration to collect blood and splenic tissue. The proportion of T cells including CD8+ and CD4+ T cells, Th1 and Th2 in peripheral blood of experimental mice were measured by flow cytometric. The protein level in serum and mRNA level in splenic tissue of experimental mice for interleukin (IL)-2, IL-12, interferon-γ (IFN-γ), IL-4, IL-6, IL-10 and IL-13 were measured by enzyme linked immunosorbent assay and fluorescence quantitative polymerase chain reaction respectively., Results: HSPT elevated the proportion of T cells including both CD8+ and CD4+ T cells, in which the proportion of Th1 and Th2 cells increased, while the ratio of Th1/Th2 cells decreased in peripheral blood of the immunosuppressed mouse model with Th1 to Th2 shift induced by CsA. Furthermore, HSPT elevated both protein and mRNA level of Th1-type cytokines IL-2 and IFN-γ, while had no significant effect on protein and mRNA level of Th1-type cytokine IL-12 and Th2-type cytokines IL-4, IL-6, IL-10, IL- 13 in mouse model., Conclusion: Our findings suggest that HSPT can increase proportion of T cells including both CD8+ and CD4+ T cells and induce Th2 to Th1 shift in both cells and cytokines, which probably was the mechanism to account for the adjuvant therapeutic efficacy of HSPT on RRI and AIDS.

The melanocortin-3 receptor (MC3R) and melanocortin-4 receptor (MC4R), known as neural melanocortin receptors, have been implicated to be critical components of the hypothalamic leptin-melanocortin pathway and related to obesity pathogenesis. In contrast to extensive evidence from physiologic, biological, genetic studies demonstrating that MC4R is a critical regulator in obesity, whether MC3R mutation causes obesity is still controversial. In the present study, we screened for coding variants in the MC3R gene of 176 obese individuals (mean BMI 34.84 ± 0.19 kg/m 2 ) and 170 lean controls (mean BMI 20.70 ± 0.08 kg/m 2 ) to assess the prevalence of MC3R mutations in a Chinese cohort. Two novel mutations, A33D (c.C98 > A) and A259T (c.G775 > A), were identified in two subjects with morbid obesity, respectively. A259T was also identified in the carrier's sibling. In vitro functional studies showed that A33D was defective in the cAMP signaling pathway, whereas A259T MC3R had defective maximal binding and cAMP generation in response to NDP- and α-MSH, likely due to decreased cell surface expression. In addition, we showed that A33D and A259T were biased receptors and defect in constitutive activation of ERK1/2 signaling through MC3R might be a cause for morbid obesity. Our sequencing and co-segregation studies combined with comprehensive functional analysis demonstrated that A259T might be predisposing to obesity. Further investigations in larger cohorts will be needed in order to define this association and the specific phenotypic characteristics resulting from these mutations., (Copyright © 2021. Published by Elsevier B.V.)

Skeletogenesis is a complex process that requires a rigorous control at multiple levels during osteogenesis, such as signaling pathways and transcription factors. The skeleton among vertebrates is a highly conserved organ system, but teleost fish and mammals have evolved unique traits or have lost particular skeletal elements in each lineage. In present study, we constructed a skeletogenesis database containing 4101, 3715, 2996, 3300, 3719 and 3737 genes in Danio rerio, Oryzias latipes, Gallus gallus, Xenopus tropicalis, Mus musculus and Homo sapiens genome, respectively. Then, we found over 55% of the genes are conserved in the six species. Notably, there are 181 specific-genes in the human genome without orthologues in the other five genomes, such as the ZNF family (ZNF100, ZNF101, ZNF14, CALML6, CCL4L2, ZIM2, HSPA6, etc); and 31 genes are identified explicitly in fish species, which are mainly involved in TGF-beta, Wnt, MAPK, Calcium signaling pathways, such as bmp16, bmpr2a, eif4e1c, wnt2ba, etc. Particularly, there are 20 zebrafish-specific genes (calm3a, si:dkey-25li10, drd1a, drd7, etc) and one medaka-specific gene (c-myc17) that may alter skeletogenesis formation in the corresponding species. The database provides the new systematic genomic insights into skeletal development from teleosts to mammals, which may help to explain some of the complexities of skeletal phenotypes among different vertebrates and provide a reference for the treatment of skeletal diseases as well as for applications in the aquaculture industry., (Copyright © 2021. Published by Elsevier Inc.)

Background: Exposure to perfluoroalkyl acids (PFAAs) is known to be associated with metabolic disorders. However, whether PFAAs isomers are associated with metabolic syndrome (MetS) still remains unknown., Objectives: To explore the associations between serum PFAAs isomers and MetS., Methods: We recruited 1,501 adults from a cross-sectional study, the "Isomers of C8 Health Project in China" to investigate the associations between PFAAs isomers and MetS. A total of 20 PFAAs including the isomers of PFOS and PFOA were detected. Logistic regression models and restricted cubic spline models were used to evaluate the relationship of serum PFAAs isomers exposure with MetS and its components as well after adjusting for covariates., Results: The MetS prevalence in our study was 43.0%. The serum levels of both PFOS and PFOA isomers were higher in participants with MetS than that with non-MetS (p < 0.05). We found positive associations for per natural log-transformed ng/mL of branched perfluorooctane sulfonate (br-PFOS) (odds ratio (OR) = 1.18, 95% confidence interval (CI): 1.01, 1.38)) linear perfluoronanoic acid (n-PFOA) (OR = 1.35, 95% CI: 1.16, 1.58) and perfluoro-6-methylpheptanoic acid (6 m-PFOA) (OR = 1.32, 95% CI: 1.11, 1.57) with higher odds of MetS after covariates adjustment, while null association was observed for linear isomers of PFOS (OR = 1.09, 95% CI: 0.94, 1.25). We found a nonlinear dose-response relationship with a "threshold" effect in serum br-PFOS isomers with MetS, in which the odds of MetS increased quickly with increasing serum br-PFOS isomers under low exposure (p for nonlinearity = 0.030)., Conclusion: We report new evidence of associations between PFAAs isomers and MetS and the nonlinearity of dose-response relationship with br-PFOS isomers. Our findings indicate that more attention is needed to pay on the nonlinearity of dose-response relationship when investigate the association of PFAAs isomers with human health., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The surgical indications for liver hemangioma remain unclear., Methods: Data from 152 patients with hepatic hemangioma who underwent hepatectomy between 2004 and 2019 were retrospectively reviewed. We analyzed characteristics including tumor size, surgical parameters, and variables associated with Kasabach-Merritt syndrome and compared the outcomes of laparoscopic and open hepatectomy. Here, we describe surgical techniques for giant hepatic hemangioma and report on two meaningful cases., Results: Most (63.8%) patients with hepatic hemangioma were asymptomatic. Most (86.4%) tumors from patients with Kasabach-Merritt syndrome were larger than 15 cm. Enucleation (30.9%), sectionectomy (28.9%), hemihepatectomy (25.7%), and the removal of more than half of the liver (14.5%) were performed through open (87.5%) and laparoscopic (12.5%) approaches. Laparoscopic hepatectomy is associated with an operative time, estimated blood loss, and major morbidity and mortality rate similar to those of open hepatectomy, but a shorter length of stay. 3D image reconstruction is an alternative for diagnosis and surgical planning for partial hepatectomy., Conclusion: The main indication for surgery is giant (> 10 cm) liver hemangioma, with or without symptoms. Laparoscopic hepatectomy was an effective option for hepatic hemangioma treatment. For extremely giant hemangiomas, 3D image reconstruction was indispensable. Hepatectomy should be performed by experienced hepatic surgeons.

The physicochemical mechanism of starch digestion is very complicated since it may be affected by the non-valence interactions of the amylase inhibitor with the substrate or the enzyme. The role of hydrophobic interaction in the process of starch digestion is not clear. In this study, pluronics (PLs) with different hydrophobicity were used as model amphiphilic compounds to study their inhibition on starch digestion using multi-spectroscopic methods. The results showed that the hydrophobic nature of PLs changed starch structure, but it had a greater effect on the structure of α-amylase by exposing more tryptophan residues and increasing α-helix and β-sheet contents. Further investigation by using different chain-length fatty acids confirmed the results. The finding in this study is informative to design and fabricate α-amylase inhibitors for controlling starch digestion at the molecular level., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: A cylindrical piezoelectric element and a specific multi-channel circular microelectromechanical systems (MEMS)-transducer array of ultrasonic system were used for ultrasonic energy generation and ablation. A relatively long time is required for the heat to be conducted to the target position. Ultrasound thermal therapy has great potential for treating deep hyperplastic tissues and tumors, such as breast cancer and liver tumors., Methods: Ultrasound ablation technology produces thermal energy by heating the surface of a target, and the heat gradually penetrates to the target's interior. Beamforming was performed to observe energy distribution. A resonance method was used to generate ablation energy for verification. Energy was generated according to the coordinates of geometric graph positions to reach the ablation temperature., Results: The mean resonance frequency of Channels 1-8 was 2.5 MHz, and the cylindrical piezoelectric ultrasonic element of Channel A was 4.2546 Ω at 5.7946 MHz. High-intensity ultrasound has gradually been applied in clinical treatment. Widely adopted, ultrasonic hyperthermia involves the use of high-intensity ultrasound to heat tissues at 42-45 °C for 30-60 min., Conclusion: In the ultrasonic energy method, when the target position reaches a temperature that significantly reduces the cell viability (46.9 °C), protein surface modification occurs on the surface of the target.

Purpose: to describe the methodology of transurethral seminal vesiculoscopy and the anatomy of the area of the verumontanum, and to determine the safety of this procedure, especially in terms of postoperative complications., Methods: This retrospective observational study enrolled 144 patients with intractable hematospermia from May 2011 and August 2019. A 4.5/6.5-Fr vesiculoscope was inserted into the seminal vesicle to deal with the positive findings. The solution of quinolones was used to rinse each seminal vesicle., Results: In this study, Transurethral seminal vesiculoscopy was successfully performed in 139 patients (96.53%). Hematospermia was alleviated or disappeared in 116 (80.56%) patients by less than half a year after surgery. Common intraoperative manifestations were hemorrhage, stones, utricle polyps and cysts. The surgical approach in our study were categorized into four types, including 24 (16.7%), 73 (50.7%), 42 (29.2%), and 5 (3.5%) cases in Type A (natural opening of the ejaculatory duct), B (trans-duct fenestration), C (trans-utricle fenestration), and D (not founded), respectively. Sexual function change was recorded in 12 patients of 111 patients, all by the method of trans-utricle fenestration, including 8 (7.21%), 3 (2.70%), and 1 (0.90%) patients in shorter intravaginal ejaculatory latency time, worse erection hardness and loss of orgasm, respectively., Conclusion: Transurethral seminal vesiculoscopy is an effective and safe procedure for the management of hematospermia. The anatomy of the distal seminal tract should be understood more deeply and Wu'method (uncover-curtain method) needs to be promoted to verify its universality and safety. Besides, the complications of the function dysfunction should be discussed in the future in multi-center clinical trials.

Background: Recent studies suggest that household endotoxin and allergens can modify the impact of air pollutants on development of asthma; however, epidemiological evidence is limited and conflicting., Objectives: To investigate whether pet ownership modified the association between ambient air pollution and asthma in children., Methods: We conducted a population-based cross-sectional study, the Seven Northeast Cities Study in China and recruited a total of 59,754 children from 94 schools during 2012-2013. Long-term air pollutant concentrations, including airborne particulate matter with a diameter of 1 μm or less (PM 1 ), PM 2.5 , PM 10 , and nitrogen dioxide (NO 2 ) from 2009 to 2012 were estimated using a random forest model. We collected information of respiratory health in children using the Epidemiologic Standardization Project Questionnaire of the American Thoracic Society (ATS-DLD-78-A). Regression models were used to evaluate associations between pet ownership and air pollution on asthma after adjusting for potential covariates., Results: Exposure to increasing levels of air pollutants was associated with higher prevalence of asthma, but associations were significantly attenuated in children who owned pets. For example, compared to children without pets, those who owned pets did not have an increased risk of symptoms of asthma (odds ratio, 1.01, 95% confidence interval: 0.78, 1.30), wheeze (0.96, 95% confidence interval [CI]: 0.76, 1.21), and cough (1.01, 95% CI: 0.87, 1.18) for each 10 µg/m 3 increase in PM 1 (P -int  < 0.05). Similar trends were observed for other air pollutants. Dog and bird ownership decreased the associations of asthma and cough with air pollutant exposure. The main findings were consistent with a series of sensitivity analyses., Conclusion: Current pet ownership may reduce the adverse impact of long-term air pollution on childhood asthma. Longitudinal studies are needed to confirm this finding which could have important implications for public health., (© 2021 The Authors. Clinical and Translational Allergy published by John Wiley and Sons Ltd on behalf of European Academy of Allergy and Clinical Immunology.)

BACKGROUND: Because Medicare plan coverage and costs change annually and older adults, the major beneficiaries of Medicare, are faced with multiple health conditions and changing medical needs, Medicare beneficiaries should evaluate their options during open enrollment every year. However, because of the complexity of plan selection, it may be challenging for Medicare beneficiaries to make an appropriate decision from among competing options. OBJECTIVES: To (a) identify factors that beneficiaries consider having influenced their plan selection decision and (b) describe the decision-making process according to the consumer decision-making model (CDM). The 2 research questions guiding this study included (a) factors Medicare beneficiaries considered having influenced their Medicare plan selection decision and (b) characteristics of decision-making processes employed by Medicare beneficiaries. METHODS: This is a phenomenological qualitative study. Semistructured in-person or telephone interviews with Alabama residents who have Medicare as the sole insurance provider were conducted between June and August 2019. Participant recruitment continued until reaching the saturation point. Each interview session consisted of structured questions identifying characteristics of participants and open-ended questions used to elicit participant Medicare plan decisionmaking process and factors affecting their decision. Data were analyzed using content analysis with a process of qualitative inductive coding. RESULTS: Twenty participants were interviewed. Twenty codes were identified and categorized into 5 themes regarding the factors influencing plan selection decisions by beneficiaries. When making a plan selection, participants were influenced by plan attributes (including cost, coverage, access to doctors, region, quality rating, and transportation); information resources and personal assistance; knowledge about Medicare; status and changes in personal situation; and experience with Medicare. Additionally, we identified 7 codes relating to beneficiary characteristics during decision-making processes, including being proactive, setting priorities, limiting choices, evaluating plans against personal needs, acquiescing to recommendations, sticking to the status quo, and weighing trade-offs. We consulted the CDM and created a conceptual model demonstrating a 5-step Medicare plan selection decision-making process and the factors influencing that process. DISCLOSURES: This study was supported by the Auburn University Undergraduate Research Program. The authors declare no conflicts of interest. CONCLUSIONS: This study created a step-by-step decision flowchart of Medicare plan selection to illustrate the complexity of the plan selection that Medicare beneficiaries must use. We uncovered the plan selection decision-making process among Medicare beneficiaries and factors affecting that process. Drawing from the CDM and the study findings, we developed a conceptual model. Findings will help researchers and community agencies target Medicare beneficiaries with different needs for assistance and design decision-making interventions/tools to help beneficiaries make rational decisions when selecting Medicare plans. These findings suggest that health care professionals should be involved in assistance programs to maximize efficiency of Medicare plan selection and to improve monitoring and consulting mechanisms to ensure the reliability of assistance information and services.

Background: Suprapancreatic lymphadenectomy is the essence of D2 radical gastric cancer surgery. The present study aimed to describe clockwise modularized laparoscopic lymphadenectomy in the suprapancreatic area., Methods: The data from gastric cancer patients who underwent surgical treatment from September 2016 to December 2018 were collected. Patients were divided into clockwise modularized lymphadenectomy (CML) and traditional open gastrectomy (OG) groups according to the surgical treatment strategy. The propensity score matching method was utilized to balance the baseline characteristics between the two groups., Results: Finally, 551 gastric cancer patients were included in the present study. Following propensity score matching, 106 pairs of patients in the CML group and OG group were included in the final analysis. The CML group had more total examined lymph nodes (36, IQR 28-44.74 vs. 29, IQR 29-39.5, p = 0.002) and no. 9 station nodes (2, IQR 1-5 vs. 2, IQR 1-3, p = 0.007) than the OG group. There was less intraoperative blood loss (30, IQR 20-80 ml vs. 80, IQR 50-80 ml, p < 0.001) and a longer surgical duration (262.5 min, IQR 220-303.25 min vs. 232, IQR 220-255 min, p < 0.001) in the CML group than in the OG group. The incidence of postoperative complications (19.8% vs. 16.0%, p = 0.591) and postoperative hospital stay (8, IQR 7-9 days vs. 8, IQR 7-9 days, p = 0.452) were comparable between the CML and OG groups., Conclusion: Laparoscopic lymphadenectomy for gastric cancer surgery is technically demanding. Clockwise modularized laparoscopic lymphadenectomy in the suprapancreatic area can attain similar effects as traditional open surgery and without an increase in postoperative adverse events.

Background: Early diagnosis is very important for the clinical treatment of gastric cancer (GC) and colorectal cancer (CRC). We aimed to detect Golgi phosphoprotein 3 (GOLPH3) and evaluate its diagnostic value., Materials and Methods: Serum concentrations of GOLPH3 were detected by ELISA in 136 CRC patients, 102 GC patients, and 50 healthy controls at the Second Affiliated Hospital of Fujian Medical University from June 2016 to December 2019. Serum concentrations of CEA and CA19-9 were detected by ECLIA., Results: Serum concentrations of GOLPH3, CEA, and CA19-9 were higher in GC and CRC patients than in healthy controls ( P < 0.001). Serum GOLPH3 concentrations were increased in GC and CRC patients with tumors greater than 5 cm, poor differentiation, greater depth of tumor invasion, and increased lymphatic and distant metastases ( P < 0.05). In the GC and CRC groups, the AUCs of GOLPH3 were higher than those of CEA and CA19-9 ( P < 0.05), while the AUCs of the marker combination were higher than those of GOLPH3 ( P < 0.05), and postoperative serum GOLPH3 levels were lower than preoperative levels ( P < 0.001). Serum GOLPH3 concentrations in CRC patients correlated positively with CEA and CA19-9 concentrations ( P < 0.05)., Conclusion: Serum GOLPH3 concentrations in GC and CRC patients are related to TNM stage. GOLPH3 may represent a novel biomarker for the diagnosis of GC and CRC. The combination of serum GOLPH3, CEA, and CA19-9 concentrations can improve diagnostic efficiency for GC and CRC. GOLPH3 is expected to become an indicator for the early diagnosis and evaluation of surgical effects., Competing Interests: Conflicts of interest relevant to this article were not reported., (Copyright © 2021 Chun-Xiao Wang et al.)

Abstract: This study conducts a correlation exploration of CYP2C19 gene polymorphism and clopidogrel resistance in Han Chinese patients with cerebral infarction in Guizhou Region.A total of 270 Han Chinese patients with cerebral infarction, who were hospitalized in our hospital from January 2016 to January 2018, are selected. These patients were divided into 2 groups, clopidogrel resistance group (n = 60) and clopidogrel sensitive group (n = 210). According to the TEG results, the CYP2C19 gene polymorphism detection was carried out by using the PCR-RFLP method, while IL-6 level in the patient's blood was measured by using the ELISA method.The resistance group occupies 22.22%. The platelet inhibition ratio of the resistance group was 23 ± 7%, which was significantly lower than that of the sensitive group (65 ± 13%), and the difference was statistically significant (P < .05). The Logisitic regression analysis revealed that the history of diabetes, history of high blood pressure, increase in low density lipoprotein and CYP2C19 mutant gene were independent risk factors of clopidogrel resistance. After treatment, the serum IL-6 level of patients in the resistance group was 17.21 ± 0.98 ng/L, which was significant higher than that of patients in the sensitive group (11.21 ± 0.68 ng/L), and the difference was statistically significant (P < .05).Patients with cerebral infarction in Guizhou region have a higher occurrence rate of clopidogrel resistance. Clopidogrel resistance not only will weaken the anti-inflammatory action of the drug, but also correlates with the patient's CYP2C19 mutant gene and blood lipid level., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

An unprecedented asymmetric aza-Claisen rearrangement between enantioenriched α-chiral allylamines and allenones was found to proceed in the absence of catalysts and additives at room temperature. The rearrangement, followed by hydrolysis, provides convenient access to structurally diverse δ-chiral β-diketones in good to excellent yields with excellent retention of enantiopurity. This protocol proved powerful for the construction of an all-carbon quaternary stereocenter with high enantiopurity.

Traditional thermal tempering was applied to lithium disilicate (LD) glass-ceramic specimens with bar-like and disc-like shapes. The tempering process was conducted by heating the specimens to a temperature below the dynamic softening point, and then rapid cooling in silicone oil with different temperatures ranging from room-temperature to 300 °C to regulate the cooling rate. Effect of the oil-temperature on mechanical behavior of the tempered glass-ceramic was investigated. For the tempering at the lower oil-temperature (e.g., at room-temperature), it was found that the LD glass-ceramic specimens with both the bar-like and disc-like shapes could be remarkably strengthen and toughen, however, obvious anisotropy in fracture toughness was displayed by the specimens with the bar-like shape. With increasing the oil-temperature up to 250 °C, the mechanical anisotropy of the bar-like specimens could be significantly alleviated without much loss of the strengthening effect. The results can provide references for improving reliability of mechanical behavior for the tempered LD glass-ceramic by regulating the cooling condition according to specimen geometry., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

To investigated the molecular epidemiology and in vitro antifungal susceptibility of Cryptococcus isolates from West China Hospital from HIV and non-HIV patients between 2009 and 2015. A total of 132 C. neoformans and C. gattii were subjected to antifungal susceptibility testing by E-test method. Among the 132 isolates, 42 C. neoformans and C. gattii were analyzed by mating type and URA5-RFLP. A total of 113 C. neoformans and C. gattii were subjected to multi-locus sequence typing (MLST). MLST results revealed that ST5 was the major molecular type. The wild-type (WT) phenotype was seen in 91.5-100% of C. neoformans isolates for amphotericin B, 5-flucytosine, fluconazole, and voriconazole. However, 72.3% (94/130) of C. neoformans isolates were non-wild-type (non-WT) to itraconazole by E-test method. In the sixth study year, the geometric mean, MIC 50 and MIC 90 of fluconazole were the highest (P < 0.001). Among 132 patients. 52 were coinfected with HIV and 80 were HIV-negative. Isolates from HIV and non-HIV patients showed no differences in susceptibility to amphotericin B (P = 0.544), 5-flucytosine (P = 0.063), fluconazole (P = 0.570), voriconazole (P = 0.542), and itraconazole (P = 0.787). Our study showed that Cryptococcus in southwest China showed a low degree of genetic diversity. The increased MIC values of fluconazole are noted. Cryptococcus isolates from HIV and non-HIV patients have shown no differences in susceptibility to five antifungal agents.

Second-harmonic generation (SHG) in plasmonic nanostructures has been investigated for decades due to their wide applications in photonic circuit, quantum optics and biosensing. Development of large-scale, uniform, and efficient plasmonic nanostructure system with tunable modes is desirable for their feasible utilizations. Herein, we design an efficient inch-scale SHG source by a solution-processed method instead of traditional high-cost processes. By assembling the gold nanoparticles with the porous anodic alumina templates, multiresonance in both visible and near-infrared regions can be achieved in hexagonal plasmonic nanostructure arrays, which provide strong electric field enhancement at the gap region. Polarization-independence SHG radiation has been realized owing to the in-plane isotropic characteristic of assembled unit. The tilt-angle dependent and angle-resolved measurement showed that wide-angle nonlinear response is achieved in our device because of the gap geometry of ball-in-bowl nanostructure with nonlinear emission electric dipoles distributed on the concave surface, which makes it competitive in practical applications. Our progress not only makes it possible to produce uniform inch-scale nonlinear arrays through low-cost solution process; and also advances the understanding of the SHG radiation in plasmonic nanostructures.

Introduction: Marfan syndrome (MFS) is characterized by ectopia lentis (EL) and elongated axial length (AL). The characteristics of AL in young patients with MFS and bilateral EL before the lens surgery are not fully understood., Methods: This study reviewed MFS patients under 20 years old with bilateral EL from January 2015 to October 2020. The Z-scores were introduced in terms of the number of standard deviations from the mean of age-matched normative data. Using Z-scores, the distribution of AL and influence factors were evaluated. The correlations between AL and other biometrics were analyzed., Results: We reviewed 183 patients and enrolled both eyes. The mean age was 8.44 ± 4.69 years. About 36% of the patients were children under 6 years old. The median AL increased from 23.16 mm under 5 years old to 26.20 mm in the 16-20 age group, and when plotted, the trend presented a logarithmic curvature (R2 = 0.145, p < 0.001). The median Z-AL score was 1.24. One-third of eyes had Z-score <0. About 20% of the patients had AL difference over 1 mm between the right and left eyes, and the right one had longer Z-AL scores (p = 0.013). The eye complicated with megalocornea (10, 7.04%) had larger Z-AL scores (4.72 ± 3.51 vs. 1.10 ± 2.25, p = 0.002). A positive correlation was found between Z-AL and Z-corneal curvature radius (r = 0.265, p < 0.001)., Conclusion: Young patients with bilateral EL but small AL should not be excluded from MFS without systematic examination. The age-adjusted Z-score will facilitate further study of the individual variations in AL across different ages., (© 2021 The Author(s). Published by S. Karger AG, Basel.)