Publications by authors named "Xinyue Zhang"

467 Publications

Rapid screening of hepatotoxic components in Uncariae Ramulus Cum Uncis based on "component-target-pathway" network.

J Pharm Biomed Anal 2022 Jul 26;219:114968. Epub 2022 Jul 26.

Tianjin University of Traditional Chinese Medicine, No. 10 Poyang Lake Road, West Zone, Tuanbo New City, Jinghai District, Tianjin 301617, China. Electronic address:

As a multi-base source traditional Chinese medicine, the hepatotoxicity of Uncariae Ramulus Cum Uncis (URCU) has been reported repeatedly in recent years. The lack of clarity of toxic components and toxicity mechanisms is a key issue that needs to be addressed. In this article, a "component-target-pathway" network strategy was established to firstly predicting the hepatotoxic components and the toxicity mechanism of URCU. Ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) and data post-processing technology were used to classify and identify the main components in Uncaria rhynchophylla (Miq.) Miq. ex Havil. (UR) and Uncaria sinensis (Oliv.) Havil. (US). Then, the potential hepatotoxic components were screened by network pharmacology and molecular docking. As a result, 40 components and 39 ingredients were identified in UR and US, respectively. Cadambine, rhynchophylline, corynoxeine, isocorynoxeine, strictosamide and mitraphylline were screened as the potential hepatotoxic ingredients contained both in UR and US. The network pharmacology showed that the potential hepatotoxic components could affect the IL-17 signaling pathway by regulating related targets such as MAPK1 and MAPK14, which might lead to the occurrence of liver injury. This study not only provided a reasonable strategy for the rapid screening of hepatotoxic components in URCU, but also supplied reference and guidance for the rational clinical application and scientific supervision of URCU.
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http://dx.doi.org/10.1016/j.jpba.2022.114968DOI Listing
July 2022

Immunogenicity and safety of an enterovirus 71 vaccine in children aged 36-71 months: A double-blind, randomised, similar vaccine-controlled, non-inferiority phase III trial.

EClinicalMedicine 2022 Oct 29;52:101596. Epub 2022 Jul 29.

Wuhan Institute of Biological Products Co., Ltd, Wuhan, China.

Background: The enterovirus 71 (EV71) vaccine produced by Wuhan Institute of Biological Products Co., Ltd. (WIBP) (B-EV71) has been given to children aged 6-35 months, and it has shown good safety, immunogenicity and efficacy. However, the administration of EV71 vaccine in children aged 36-71 months, which is another target population, needs further exploration.

Methods: We conducted a double-blind, randomised, controlled, non-inferiority phase III clinical trial in children aged 36-71 months, with a further comparison group of children aged 6-35 months in China. Children aged 6-71 months with no history of hand, foot and mouth disease or prior-vaccination of EV71 vaccine were eligible and recruited. Eligible participants aged 36-71 months were randomly assigned (1:1) to receive two doses of the B-EV71 vaccine (Older-B group) or the control EV71 vaccine (C-EV71 vaccine, produced by Institute of Medical Biology, Chinese Academy of Medical Sciences) (Older-C group), administered at a 30-day interval. Eligible participants aged 6-35 months were enrolled consecutively to receive two doses of the B-EV71 vaccine (Younger-B group) at a 30-day interval. Participants, investigators and those assessing outcomes were masked to the vaccine received. Non-inferiority analyses were conducted to compare the immunogenicity of EV71 vaccine in the Older-B group with that in the Older-C and Younger-B groups. Non-inferiority margins were 10% for seroconversion rate differences and 0.5 for geometric mean titre (GMT) ratios. The primary endpoints were the GMT level and seroconversion rate of anti-EV71 neutralising antibody 30 days after the second dose of vaccination. The primary analysis was performed in the per-protocol population. Safety analyses were conducted amongst participants receiving at least one dose of vaccine. This trial was registered at Chinadrugtrials.org.cn (#CTR20192345).

Findings: Between June 3 and June 30, 2020, 1600 participants were enrolled and assigned, including 625 participants in the Older-B group, 625 participants in the Older-C group and 350 participants in the Younger-B group. The seroconversion rate of anti-EV71 neutralising antibody in the Older-B group (99.66%; 95% CI: 99.18%-100.00%) was non-inferior to that of the Older-C (99.32%; 95% CI: 98.65%-99.98%) and Younger-B groups (100.00%; 95% CI: 100.00%-100.00%). The differences in seroconversion rates in the Older-B group to those in the Older-C and Younger-B groups were 0.34% (95%CI: -2.17%-2.86%) and -0.34% (95%CI: -2.78%-2.09%). The GMT of the anti-EV71 neutralising antibody in the Older-B group (693.87) was also non-inferior to that in the Older-C (289.37) and Younger-B groups (634.80). The ratios of GMTs in the Older-B group to those in the Older-C and Younger-B groups were 2.67 (95%CI: 2.00-3.00) and 1.00 (95%CI: 0.75-1.00), respectively. The incidence of any adverse event (AE) related to vaccination was similar amongst the three groups (34/625 [5.44%] in the Older-B group, 32/623 [5.14%] in the Older-C group, and 26/349 [7.45%] in the Younger-B group), with only 2 (0.57%) participants having grade 3 AEs in the Younger-B group. Fifteen (0.94%) participants from these three groups had reported serious AEs (SAEs), all of which were unrelated to vaccines.

Interpretation: EV71 vaccine produced by WIBP could extend to be administered to children aged 36-71 months against EV71 infection. However, the persistence of vaccine-induced immunities needs to be further investigated.

Funding: Hubei Province's young medical talent program (20191229), Hubei Province's young talent program (2021), Hubei Province's young public health talent program (2021); and the Wuhan Institute of Biological Products Co., Ltd.
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http://dx.doi.org/10.1016/j.eclinm.2022.101596DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9340505PMC
October 2022

Engineering monodispersed 2 nm SbS particles embedded in a porphyrin-based MOF-derived mesoporous carbon network an adsorption method to construct a high-performance sodium-ion battery anode.

Dalton Trans 2022 Jul 27. Epub 2022 Jul 27.

Department of Chemistry, Northeastern University, Shenyang 110819, People's Republic of China.

Sodium ion batteries (SIBs) are expected to replace lithium ion batteries (LIBs) as the next generation of large-scale energy storage applications because of their superior cost performance. However, the larger ionic radius of Na causes a remarkable volume expansion than that of Li during charge and discharge, which reduces the performance of the battery. In this work, we engineered a composite material in that monodispersed 2 nm SbS particles are uniformly loaded into a carbon matrix (SbS/CZM), which is obtained by carbonization of a zirconium-based MOF with adsorption of Sb. The obtained composite material has a high specific surface area in favor of mass transfer, and the porous structure can resist many volume changes in the circulation process. Moreover, the ultrafine SbS particles are well-distributed in the composite material, which increases the utilization of the active substance and is promising for the storage of Na. Based on its unique structure, the SbS/CZM composite shows a specific capacity of 550 mA h g at 100 mA g and an excellent cycling stability of 88.9% retention after 1000 cycles at 3 A g. The excellent electrochemical performance provides enlightenment for the rational design of hierarchical heterostructures for energy storage applications.
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http://dx.doi.org/10.1039/d2dt01898eDOI Listing
July 2022

The Efficacy and Underlying Mechanism of Berberine against Atherosclerosis: a Meta-analysis in Preclinical Animal Studies.

J Cardiovasc Pharmacol 2022 May 30. Epub 2022 May 30.

Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China. Tel: 13121306161; Email:

Abstract: Atherosclerosis is the primary cause of many cardiovascular diseases, and an increasing number of studies have shown that Berberine could delay plaque formation and development. Therefore, we aimed to evaluate its effects and explore its mechanisms in this meta-analysis. We searched PubMed, Embase, Cochrane Library, CNKI, Wanfang and VIP databases for original preclinical studies to conduct meta-analysis. Twelve articles (16 studies; 312 ApoE-/- mice) were included, and all the studies scored 3-5 points according to SYRCLE's risk of bias tool. Berberine could significantly decrease plaque area and plaque macrophage content (plaque area, SMD=-2.02, 95%CI: -2.80 to -1.24, P=0.000; plaque macrophage content, SMD=-4.28, 95%CI: -7.67 to -0.88, P=0.013), lower the levels of TC, TG, LDL (TC, SMD=-1.47, 95%CI: -2.20 to -0.74, P=0.000; TG, SMD=-0.77, 95%CI: -1.21 to -0.33, P=0.000; LDL, SMD=-0.61, 95%CI: -1.11 to -0.11, P=0.000), change the secretion of inflammatory cytokines (IL-1β, SMD=-2.29, 95%CI: -3.40 to -1.18, P=0.000; IL-6, SMD=-1.48, 95%CI: -2.11 to -0.85, P=0.008; TNF-α, SMD=-1.98, 95%CI: -3.01 to -0.94, P=0.000; IL-10, SMD=1.78, 95%CI: 0.76 to 2.80, P=0.015), but there were no significant differences in HDL levels and plaque lipid content (HDL, SMD=0.02, 95%CI: -0.35 to 0.40, P=0.021; plaque lipid content, SMD=-6.85, 95%CI: -21.09 to 7.39, P=0.007). The results were robust across a range of sensitivity analyses. Therefore, the results indicate that Berberine is a promising drug for the treatment of atherosclerosis through regulating lipid metabolism, inflammation and plaque composition. However, some potential mechanisms remain to be further elucidated.
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http://dx.doi.org/10.1097/FJC.0000000000001308DOI Listing
May 2022

Effects of insomnia and levels of depression and anxiety symptoms on quality of life in people with epilepsy.

BMC Psychiatry 2022 07 25;22(1):497. Epub 2022 Jul 25.

Department of Neurology, The First Hospital of Jilin University, Changchun, China.

Objectives: The association between insomnia and quality of life (QOL) in epilepsy is poorly understood and may involve interactive variables. We aimed to investigate whether and how insomnia, levels of depression and anxiety symptoms interact to influence QOL in people with epilepsy (PWE).

Methods: A consecutive cohort of 179 PWE was enrolled. We collected data on insomnia, levels of depression and anxiety symptoms, and QOL. The Insomnia Severity Index (ISI), Depression Inventory for Epilepsy (NDDI-E), Generalized Anxiety Disorder-7 (GAD-7), and QOL in Epilepsy Inventory (QOLIE-31) were used. The direct, indirect, and total effects of insomnia on QOL were estimated based on a moderated mediation model.

Results: Depression symptom levels mediated the association between insomnia and QOL (B = 0.09 SE = 0.03, p = 0.01). Depression symptom levels accounted for 34.7% of the total effect of insomnia on QOL. The mediating effect of depression symptom levels was positively moderated by anxiety symptom levels (B = 0.09, SE = 0.03, p = 0.01).

Conclusion: The effect of insomnia on QOL can be partially explained by the mediation of depression symptom levels. Additionally, improving anxiety symptoms may attenuate the indirect effect of insomnia on QOL through depression symptom levels.
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http://dx.doi.org/10.1186/s12888-022-04154-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9317410PMC
July 2022

A novel missense variant c.71G > T (p.Gly24Val) of the CRYBA4 gene contributes to autosomal-dominant congenital cataract in a Chinese family.

Int Ophthalmol 2022 Jul 16. Epub 2022 Jul 16.

Department of Medical Genetics, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, China.

Purpose: To investigate the potential genetic defects in a five-generation Chinese family with autosomal dominant congenital cataract (ADCC).

Methods: Whole exome sequencing was performed to search the variants in the candidate genes associated with congenital cataract. Sanger sequencing was used to validate the variants and examine their co-segregation in the patients and their relatives. The potential effect of the variants was analyzed using several bioinformatic methods and further examined through Western blotting and co-immunoprecipitation.

Results: A missense variant c. 71 G > T (p. Gly24Val) in the CRYBA4 gene, a known ADCC candidate gene, was identified to be heterozygously present in the patients and co-segregate with cataract in the family. The mutation was absent in all of the searched databases, including our in-house exome sequences of 10,000 Chinese. The alignments of the amino acid sequences of CRYBA4 in a variety of species revealed that the amino acid residue Gly24 was evolutionarily highly conserved, and the in silico analysis predicted that the missense mutation of Gly24Val was damaging for the protein structure and function of CRYBA4. Then, the in vitro expression analysis further revealed that the Gly24Val mutation in CRYBA4 inhibited its binding with CRYBB1. The impaired interaction of β-crystallin proteins may affect their water-solubility and contribute to the formation of precipitates in lens fiber cells.

Conclusion: We identified a novel missense variant in the CRYBA4 gene as a pathogenic mutation of ADCC in a Chinese family. Our finding expanded the CRYBA4 variation spectrum associated with congenital cataracts.
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http://dx.doi.org/10.1007/s10792-022-02386-3DOI Listing
July 2022

Effects of surface treatment and shade on the color, translucency, and surface roughness of high-translucency self-glazed zirconia materials.

J Prosthet Dent 2022 Jul 8. Epub 2022 Jul 8.

Associate Professor, Department of General Dentistry, Peking University School and Hospital of Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Beijing, PR China. Electronic address:

Statement Of Problem: The impact of different surface treatments and shades on the color, translucency, and surface roughness of high-translucency self-glazed zirconia materials is unclear.

Purpose: The purpose of this in vitro study was to investigate the effects of different external surface treatments (self-glazed, milled, polished, and glazed), intaglio surface treatments (milled and airborne-particle abraded), and shades (A1 and A3 shades) on the color, translucency, and surface roughness of high-translucency self-glazed zirconia materials, as well as the correlations among optical parameters, translucency, and surface roughness.

Material And Methods: Eighty shade A1 and 80 shade A3 disks were fabricated with a thickness of 0.80 ±0.02 mm and divided into 16 groups (n=10). Different external and intaglio surface treatments were applied to the specimens. CIELab values were measured with a spectrophotometer, and color differences (ΔE) and relative translucency parameter (RTP) were calculated. Total transmittance (Tt%) and reflectance (R%) were tested with a spectrophotometer equipped with an integrating sphere. Surface roughness (Ra and Rz) (μm) was measured with a noncontact 3-dimensional laser scanning microscope. One specimen from each group was subjected to scanning electron microscope (SEM) examination. Data were analyzed with ANOVA and the Tukey post hoc test. The correlation among optical parameters, translucency, and surface roughness was investigated by using Pearson correlation analysis (α=.05).

Results: The effects of external surface treatments, intaglio airborne-particle abrasion, and shades on ΔE, RTP, and Ra values of the disks were significantly different (P<.001). The smoothest external polishing surface had the greatest RTP and color difference (P<.001). Shade A3 disks had lower RTP and Tt% values than shade A1 disks (P<.001). ΔE had a highly positive relationship with the RTP (A1: r=0.884, P<.001; A3: r=0.859, P<.001). SEM images demonstrated that surface treatments affected the surface texture of monolithic zirconia ceramics.

Conclusions: Different surface treatments affected the surface roughness, translucency, and final color of zirconia materials. The smoothest external polishing surface had the greatest RTP and color difference. Different shades influenced the translucency, as the darker the disk shade, the lower the translucency. The RTP was appropriate as an auxiliary indicator for evaluating the color of a dental ceramic.
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http://dx.doi.org/10.1016/j.prosdent.2022.05.014DOI Listing
July 2022

Learning Curve of USgHIFU Ablation for Uterine Fibroids: A Multi-Center Prospective Study.

J Ultrasound Med 2022 Jul 8. Epub 2022 Jul 8.

State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, China.

Objectives: To verify the stability of high-intensity focused ultrasound (HIFU) technology and the feasibility of training programs with learning curve cumulative summation (LC-CUSUM).

Methods: A total of 12 physicians and 720 cases were equally assigned to the learning group and the control group, with 6 physicians and 360 cases per group. The learning group was treated by physicians without HIFU experience and the control group was treated by experienced physicians. Nonperfused volume (NPV) ratio was assessed by contrast-enhanced magnetic resonance imaging. Technical failure was defined as NPV ratio of uterine fibroids <70% and/or major complication, while <80% was set as a stricter standard of training qualification. LC-CUSUM was used to analyze the learning curve.

Results: Physicians with or without HIFU experience in both groups achieved matchable NPV ratios, where a NPV ratio of 92.52% (16.06) was achieved by experienced physicians and 93.82% (16.95) by inexperienced physicians. No major complication was observed. The results of LC-CUSUM analysis showed that, with the standards of the NPV ratio of 70% or 80%, the learning group mastered the technique on the 11th case and the 16th case, respectively, while the control group was stable.

Conclusions: HIFU technology stayed stable in operation, with good safety and sound effectiveness, and was easy to learn. NPV ratio of 70% was considered as an appropriate indicator of training qualification. HIFU has remarkable prospects in achieving a NPV ratio of ≥80% without safety being compromised.
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http://dx.doi.org/10.1002/jum.16056DOI Listing
July 2022

Poly(maleic anhydride-alt-1-octadecene)-based bioadhesive nanovehicles improve oral bioavailability of poor water-soluble gefitinib.

Drug Dev Ind Pharm 2022 Jul 14:1-8. Epub 2022 Jul 14.

State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.

The poor water solubility and inadequate oral bioavailability of gefitinib (Gef) remain a critical issue to achieve the therapeutic outcomes. Herein, we designed a poly(maleic anhydride-alt-1-octadecene) (PMA/C18) based lipid nanovehicle (PLN) to improve the intestinal absorption and oral bioavailability of poorly water-soluble Gef. PLN was nanometer-sized particles, and Gef was dispersed in the PLN formulation as amorphous or molecular state. At 4 h of oral administration, the tissue concentration of Gef in duodenum, jejunum, and ileum was profoundly enhanced 3.37-, 8.94-, and 8.09-fold by PLN when comparing to the counterpart lipid nanovehicle. Moreover, the oral bioavailability of Gef was significantly enhanced 2.48-fold by the PLN formulation when comparing to the free drug suspension. Therefore, this study provides an encouraging bioadhesive delivery platform to improve the oral delivery of poorly water-soluble drugs.
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http://dx.doi.org/10.1080/03639045.2022.2098316DOI Listing
July 2022

Comprehensive Analysis of Gut Microbiota and Fecal Bile Acid Profiles in Children With Biliary Atresia.

Front Cell Infect Microbiol 2022 17;12:914247. Epub 2022 Jun 17.

Department of Neonatal Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.

Background: Biliary atresia (BA) is the most common cholestatic liver disease in neonates. Herein, we aimed at characterizing the gut microbiota and fecal bile acid profiles of BA patients, defining the correlations between them, and evaluating the relationship between the clinical pathogenesis and changes in the gut microbiota and bile acid profiles.

Methods: A total of 84 fecal samples from BA patients (n = 46) and matched healthy controls (HCs, n = 38) were subjected to sequencing by 16S rRNA gene amplification, and fecal bile acid were analyzed by targeted metabolomics.

Findings: Compared with the controls, a structural separation of the intestinal flora of BA patients was uncovered, which was accompanied by changes in the composition of fecal bile acids. In the BA group, , , and were enriched in patients without cholangitis ( < 0.05). and were more abundant in patients without recurrent cholangitis episodes ( < 0.05), while and were enriched in patients with multiple recurrences of cholangitis ( < 0.05). Postoperative jaundice clearance was associated with and ( < 0.05), and tauroursodeoxycholic acid was associated with jaundice clearance ( < 0.001).

Conclusion: BA patients are characterized by different compositions of gut microbiota and bile acids, and their interaction is involved in the process of liver damage in BA, which may be closely related to the occurrence of postoperative cholangitis and jaundice clearance.
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http://dx.doi.org/10.3389/fcimb.2022.914247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9247268PMC
July 2022

Relapses of Anti-NMDAR, Anti-GABABR and Anti-LGI1 Encephalitis: A Retrospective Cohort Study.

Front Immunol 2022 9;13:918396. Epub 2022 Jun 9.

Department of Neurology, The First Hospital of Jilin University, Changchun, China.

Objective: To investigate the relapse rate and study the factors that may predict the subsequent relapse in anti-NMDAR, anti-GABABR and anti-LGI1 encephalitis in Northeast China.

Methods: In the retrospective cohort study, we consecutively enrolled patients with anti-N1MDAR, anti-GABABR and anti-LGI1 encephalitis between March 2015 and November 2021. The patients were followed up for at least 6 months. The outcome variable was a binary variable of relapse or not. Predictors of relapse were identified.

Results: A total of 100 patients were enrolled. Relapse occurred in 26 (26%) patients after a median follow-up of 18 months since the first event. The relapse rates of anti - NMDAR, anti - GABABR and anti - LGI1 encephalitis were 25%, 33.3%, and 28.6%, respectively. The multivariable analysis results suggested that immunotherapy delay at the acute phase was independently associated with an increased risk of relapse in total patients (HR = 2.447, 95% CI = 1.027 - 5.832; P = 0.043). Subgroup analysis results showed that antibody titer was associated with the likelihood of relapse in anti-LGI1 encephalitis. The higher the concentration, the more likely it was for patients to have relapse (p=0.019).

Conclusion: The general relapse rate of anti-NMDAR, anti-GABABR and anti-LGI1 encephalitis was 26%. The risk of subsequent relapse was elevated in those with delayed immunotherapy in the first episode. In subgroup of anti-LGI1 encephalitis, higher antibody titer was the risk factors of relapse. Thus, timely and aggressive immunotherapy may be beneficial for patients to prevent subsequent relapse.
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http://dx.doi.org/10.3389/fimmu.2022.918396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9218051PMC
June 2022

Factors for recurrence in acute central serous chorioretinopathy patients underwent one-third dose verteporfin photodynamic therapy.

Photodiagnosis Photodyn Ther 2022 Jun 23;39:102984. Epub 2022 Jun 23.

Department of Ophthalmology, Shenyang Fourth People's Hospital, Shenyang 110031, China. Electronic address:

Purpose: To investigate the factors for recurrence in acute central serous chorioretinopathy (aCSC) for patients who underwent one-third dose verteporfin photodynamic therapy (PDT).

Materials And Methods: A retrospective study was performed in aCSC patients treated with one-third dose PDT and followed up for 36 months. Demographic information and clinical features were compared. A logistic regression model was used to evaluate the associated factor of aCSC recurrence.

Results: There were 162 patients with aCSC included in current study. 36-month after one-third dose PDT, good recovery was identified in 131 patients (80.86%), whereas 31 cases (19.14%) developed recurrence. Significant between-group differences were observed in baseline age, the right, left and both eyes, best-corrected visual acuity (BCVA), presenting with pigment epithelium detachment (PED), retinal pigment epithelium (RPE) damage and subfoveal choroidal thickness (SCT) level (P = 0.005, P < 0.001, P < 0.001, P < 0.001, P = 0.006, and P < 0.001, respectively). The recurrence of aCSC was associated with presenting with PED (odds ratio = 1.78; 95% CI, 1.45-1.98; P < 0.001), RPE damage (OR = 1.13; 95%CI: 1.08-1.23; P < 0.001), baseline BCVA (OR = 0.96; 95%CI: 0.95 - 0.99; P = 0.001), and SCT level (OR = 1.18; 95%CI: 1.02-1.20; P < 0.001).

Conclusion: In acute CSC after treatment of one-third dose PDT, recurrence is associated with RPE damage, baseline BCVA and SCT level. Our findings will assist clinicians to evaluate aCSC in clinical practice and provide insights into the prevention of recurrence.
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http://dx.doi.org/10.1016/j.pdpdt.2022.102984DOI Listing
June 2022

Facial emotion perception abilities are related to grey matter volume in the culmen of cerebellum anterior lobe in drug-naïve patients with first-episode schizophrenia.

Brain Imaging Behav 2022 Jun 25. Epub 2022 Jun 25.

Nanjing Brain Hospital, Nanjing Medical University, Nanjing, 210029, China.

Impaired capability for understanding and interpreting the expressions on other people's faces manifests itself as a core feature of schizophrenia, contributing to social dysfunction. With the purpose of better understanding of the neurobiological basis of facial emotion perception deficits in schizophrenia, we investigated facial emotion perception abilities and regional structural brain abnormalities in drug-naïve patients with first-episode schizophrenia, and then examined the correlation between them. Fifty-two drug-naive patients with first-episode schizophrenia and 29 group-matched healthy controls were examined for facial emotion perception abilities assessed with the Facial Emotion Categorization and performed magnetic resonance imaging. The Facial Emotion Categorization data were inserted into a logistic function model so as to calculate shift point and slope as outcome measurements. Voxel-based morphometry was applied to investigate regional grey matter volume (GMV) alterations. The relationship between facial emotion perception and GMV was explored in patients using voxel-wise correlation analysis within brain regions that showed a significant GMV alterations in patients compared with controls. The schizophrenic patients performed differently on Facial Emotion Categorization tasks from the controls and presented a higher shift point and a steeper slope. Relative to the controls, patients showed GMV reductions in the superior temporal gyrus, middle occipital gyrus, parahippocampa gyrus, posterior cingulate, the culmen of cerebellum anterior lobe, cerebellar tonsil, and the declive of cerebellum posterior lobe. Importantly, abnormal performance on Facial Emotion Categorization was found correlated with GMV alterations in the culmen of cerebellum anterior lobe in schizophrenia. This study suggests that reduced GMV in the culmen of cerebellum anterior lobe occurs in first-episode schizophrenia, constituting a potential neuropathological basis for the impaired facial emotion perception in schizophrenia.
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http://dx.doi.org/10.1007/s11682-022-00677-yDOI Listing
June 2022

Comparison of the Effects of 5-Hydroxymethylfurfural in Milk Powder Matrix and Standard Water on Oxidative Stress System of Zebrafish.

Foods 2022 Jun 20;11(12). Epub 2022 Jun 20.

Hubei Key Laboratory of Edible Wild Plants Conservation and Utilization, Hubei Normal University, Huangshi 435002, China.

5-Hydroxymethylfurfural (5-HMF) and furfural (FF) are products of the maillard reaction (MR) in milk powder and their safety is controversial. The concentration changes of 5-HMF and FF after a period of cold storage were determined by high-performance liquid chromatography (HPLC). Then, we compared the toxicity effects of 5-HMF (2, 20, or 200 μM) in milk powder matrix and standard water on the oxidative stress system of zebrafish embryos. The results showed that the concentration of 5-HMF was stable, and the concentration of FF degraded over time. 5-HMF-exposed zebrafish embryos had a LC value of 961 μM for 120 h. High-concentration of 5-HMF exposure resulted in developmental toxicity and induced oxidative stress. 5-HMF exposure resulted in low expression of gene at 200 μM in both matrices. Moreover, , , , and genes were differentially highly expressed in other groups or showed no significant difference. Residual levels in all groups were well below the exposed dose, with a maximum value of only 0.4‱. These results provided a theoretical basis for understanding the effects of 5-HMF exposure in milk powder matrix on the oxidative stress system and suggested that the presence of 5-HMF in our daily consumption of milk powder does not produce significant toxic effects and need not be overstressed.
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http://dx.doi.org/10.3390/foods11121814DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9223135PMC
June 2022

Atmospheric-Temperature Chain Reaction towards Ultrathin Non-Crystal-Phase Construction for Highly Efficient Water Splitting.

Chemistry 2022 Jun 20:e202200683. Epub 2022 Jun 20.

College of Materials Science and Engineering, Institute for Graphene Applied Technology Innovation, Qingdao University, Qingdao, 266071, P. R. China.

Combining the self-sacrifice of a highly crystalline substance to design a multistep chain reaction towards ultrathin active-layer construction for high-performance water splitting with atmospheric-temperature conditions and an environmentally benign aqueous environment is extremely intriguing and full of challenges. Here, taking cobalt carbonate hydroxides (CCHs) as the initial crystalline material, we choose the Lewis acid metal salt of Fe(NO ) to induce an aqueous-phase chain reaction generating free CO ions with subsequent instant FeCO hydrolysis. The resultant ultrathin (∼5 nm) amorphous Fe-based hydroxide layer on CCH results in considerable activity in catalyzing the oxygen evolution reaction (OER) and hydrogen evolution reaction (HER), yielding 10/50 mA ⋅ cm at overpotentials of 230/266.5 mV for OER and 72.5/197.5 mV for HER. The catalysts can operate constantly in 1.0 M KOH over 48 and 45 h for the OER and HER, respectively. For bifunctional catalysis for alkaline electrolyzer assembly, a cell voltage as low as 1.53 V was necessary to yield 10 mA cm (1.7 V at 50 mA cm ). This work rationally builds high-efficiency electrochemical bifunctional water-splitting catalysts and offers a trial in establishing a controllable nanolevel ultrathin lattice disorder layer through an atmospheric-temperature chemical route.
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http://dx.doi.org/10.1002/chem.202200683DOI Listing
June 2022

Network Pharmacology Analysis and Experimental Verification Strategies Reveal the Action Mechanism of Danshen Decoction in Treating Ischemic Cardiomyopathy.

Evid Based Complement Alternat Med 2022 2;2022:7578055. Epub 2022 May 2.

State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Macau, China.

Background: Danshen Decoction comprises , , and . It can promote blood circulation and remove blood stasis, and is commonly used in the treatment of gastric and duodenal ulcers, coronary heart disease, angina pectoris, etc. This research is based on network pharmacology and is experimentally verified to explore the potential mechanism of Danshen Decoction in the treatment of ischemic cardiomyopathy (ICM).

Methods: The effective components and targets of Danshen Decoction were firstly extracted from Traditional Chinese Medicine Systems Pharmacology (TCMSP) Database and Analysis Platform, the drug-component-target-disease network was then constructed, the protein-protein interaction (PPI) network was constructed, the Gene Ontology (GO) enrichment analysis was carried out, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway was analyzed in order to find the potential active components and therapeutic mechanisms. Finally, the hypoxia/reoxygenation model in H9c2 cells was established to verify the predicted active components and therapeutic mechanisms.

Results: The results showed that Danshen Decoction has 67 potential active components and 109 therapeutic targets in treating ICM. These targets were rich in a variety of gene functions and different signaling pathways; the main gene targets include TP53, c-Jun, and Akt1. Go enrichment analysis showed that response to drug, membrane raft, and G protein-coupled amine receiver activity rank first in each process, and the main signaling pathways include PI3K-Akt signaling pathway. Through molecular docking and experimental verification of the major active components and core therapeutic targets, the active components of Danshen Decoction demonstrated an ability to reduce the cell damage caused by hypoxia/reoxygenation in H9c2 cells by regulating the core therapeutic target including Akt1, c-Jun, and TP53.

Conclusion: Danshen Decoction has the effect of treating ICM in multiple ways, which is consistent with the results of network pharmacology. This laid a foundation for further study in exploring the active principles and pharmacological mechanism of Danshen Decoction.
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http://dx.doi.org/10.1155/2022/7578055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9205745PMC
May 2022

Synergistic effect of oxidation etching and phase transformation triggered by controllable ion-bath microenvironments toward constructing ultra-thin porous nanosheets for accelerated industrial water splitting at high current density.

J Colloid Interface Sci 2022 Nov 2;625:50-58. Epub 2022 Jun 2.

College of Materials Science and Engineering, Institute for Graphene Applied Technology Innovation, Qingdao University, Qingdao 266071, China; College of Materials Science and Engineering, Linyi University, Linyi, Shandong, 276000, China. Electronic address:

Precisely tailoring the structure of inorganic materials at the micron and nanometer scales, especially in collaboration with component customization to design efficient, stable and low-cost transition-metal-based catalysts for industrial electrocatalytic water splitting (EWS) is a key renewable energy technology, but still facing a daunting challenge. Here, the controllable escape of Ni atom is adopted to disturb the hydrothermal ion-bath environment, thereby resulting in the coexistence of high valence Ni and Fe ions. Combined with a one-step hydrothermal coordination strategy, the timeline-adjusted ion-bath microenvironment can effectively trigger the phase transformation of carbonate hydroxide hydrate nanosheets (NFCH) to nickel ferrite intercalated NFCH ultra-thin porous nanosheets (NF-CH-O). Thanks to the high-energy phase boundary synergistic effect and the rapid mass transfer advantages of ultra-thin porous nanostructures, the as-prepared NF-CH-O nanosheets exhibit remarkable oxygen and hydrogen evolution reaction (OER/HER) catalytic activity and stability, with low overpotentials of 207/191 mV at 50 mA cm, respectively, as well as the activity retention for 100 h. The alkaline water electrolyzer set up with NF-CH-O as both anodic and cathodic electrodes only requires a cell potential of 1.688 V to reach 50 mA cm in a continuous operation of 100 h. More impressively, NF-CH-O only requires overpotentials of 266, 292 mV and 1.877 V to drive high current densities up to 500 mA cm for OER, HER and EWS, respectively, and exhibits excellent stability with a reduction in the activity of less than 10% over cycles of more than 65 h. This work highlights the room-temperature controllable ion-bath oxidative etching strategy to design efficient bifunctional catalysts with ultra-thin porous structure and high-current-density activity. Meanwhile, combined with the advantages of direct growth on the substrate for mass production, such meticulous consideration of nanostructured design will be more competitive in the H-production industry.
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http://dx.doi.org/10.1016/j.jcis.2022.05.162DOI Listing
November 2022

Pearl-inspired graphene oxide-collagen microgel with multi-layer mineralization through microarray chips for bone defect repair.

Mater Today Bio 2022 Jun 30;15:100307. Epub 2022 May 30.

Department of Plastic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

Biomineralization of natural polymers in simulated body fluid (SBF) can significantly improve its biocompatibility, osteoconductivity, and osteoinductivity because of the hydroxyapatite (HAp) deposition. Nevertheless, the superficial HAp crystal deposition hamper the deep inorganic ions exchange in porous microgels, thus gradually leading to a nonuniform regeneration effect. Inspired by the pearl forming process, this article uses the microarray chips to fabricate the multi-layer mineralized graphene oxide (GO)-collagen (Col)-hydroxyapatite (HAp) microgel, denoted as MMGCH. These fabricated MMGCH microgels exhibit porous structure and uniform HAp distribution. Furthermore, the suitable microenvironment offered by microgel promotes the time-dependent proliferation and osteogenic differentiation of stem cells, which resulted in upregulated osteogenesis-related genes and proteins, such as alkaline phosphatase, osteocalcin, and collagen-1. Finally, the MMGCH microgels possess favorable bone regeneration capacities both in cranial bone defects and mandibular bone defects via providing a suitable microenvironment for host-derived cells to form new bone tissues. This work presents a biomimetic means aiming to achieve full-thickness and uniform HAp deposition in hydrogel for bone defect repair.
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http://dx.doi.org/10.1016/j.mtbio.2022.100307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9189211PMC
June 2022

Human midbrain dopaminergic neuronal differentiation markers predict cell therapy outcomes in a Parkinson's disease model.

J Clin Invest 2022 Jul;132(14)

Institute of Neuroscience, Key Laboratory of Primate Neurobiology, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China.

Human pluripotent stem cell-based (hPSC-based) replacement therapy holds great promise for the treatment of Parkinson's disease (PD). However, the heterogeneity of hPSC-derived donor cells and the low yield of midbrain dopaminergic (mDA) neurons after transplantation hinder its broad clinical application. Here, we have characterized the single-cell molecular landscape during mDA neuron differentiation. We found that this process recapitulated the development of multiple but adjacent fetal brain regions including the ventral midbrain, the isthmus, and the ventral hindbrain, resulting in a heterogenous donor cell population. We reconstructed the differentiation trajectory of the mDA lineage and identified calsyntenin 2 (CLSTN2) and protein tyrosine phosphatase receptor type O (PTPRO) as specific surface markers of mDA progenitors, which were predictive of mDA neuron differentiation and could facilitate high enrichment of mDA neurons (up to 80%) following progenitor cell sorting and transplantation. Marker-sorted progenitors exhibited higher therapeutic potency in correcting motor deficits of PD mice. Different marker-sorted grafts had a strikingly consistent cellular composition, in which mDA neurons were enriched, while off-target neuron types were mostly depleted, suggesting stable graft outcomes. Our study provides a better understanding of cellular heterogeneity during mDA neuron differentiation and establishes a strategy to generate highly purified donor cells to achieve stable and predictable therapeutic outcomes, raising the prospect of hPSC-based PD cell replacement therapies.
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http://dx.doi.org/10.1172/JCI156768DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9282930PMC
July 2022

Inhibition of histone acetyltransferase GCN5 by a transcription factor FgPacC controls fungal adaption to host-derived iron stress.

Nucleic Acids Res 2022 Jun 10. Epub 2022 Jun 10.

State Key Laboratory of Rice Biology, the Key Laboratory of Molecular Biology of Crop Pathogens and Insects, Institute of Biotechnology, Zhejiang University, Hangzhou, China.

Poaceae plants can locally accumulate iron to suppress pathogen infection. It remains unknown how pathogens overcome host-derived iron stress during their successful infections. Here, we report that Fusarium graminearum (Fg), a destructive fungal pathogen of cereal crops, is challenged by host-derived high-iron stress. Fg infection induces host alkalinization, and the pH-dependent transcription factor FgPacC undergoes a proteolytic cleavage into the functional isoform named FgPacC30 under alkaline host environment. Subsequently FgPacC30 binds to a GCCAR(R = A/G)G element at the promoters of the genes involved in iron uptake and inhibits their expression, leading to adaption of Fg to high-iron stress. Mechanistically, FgPacC30 binds to FgGcn5 protein, a catalytic subunit of Spt-Ada-Gcn5 Acetyltransferase (SAGA) complex, leading to deregulation of histone acetylation at H3K18 and H2BK11, and repression of iron uptake genes. Moreover, we identified a protein kinase FgHal4, which is highly induced by extracellular high-iron stress and protects FgPacC30 against 26S proteasome-dependent degradation by promoting FgPacC30 phosphorylation at Ser2. Collectively, this study uncovers a novel inhibitory mechanism of the SAGA complex by a transcription factor that enables a fungal pathogen to adapt to dynamic microenvironments during infection.
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http://dx.doi.org/10.1093/nar/gkac498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9226496PMC
June 2022

Immune-Associated Gene Signatures Serve as a Promising Biomarker of Immunotherapeutic Prognosis for Renal Clear Cell Carcinoma.

Front Immunol 2022 24;13:890150. Epub 2022 May 24.

Department of Radiation Oncology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

As the most common type of renal cell carcinoma (RCC), the renal clear cell carcinoma (ccRCC) is highly malignant and insensitive to chemotherapy or radiotherapy. Although systemic immunotherapies have been successfully applied to ccRCC in recent years, screening for patients who can benefit most from these therapies is still essential and challenging due to immunological heterogeneity of ccRCC patients. To this end, we implemented a series of deep investigation on the expression and clinic data of ccRCC from The Cancer Genome Atlas (TCGA) International Consortium for Cancer Genomics (ICGC). We identified a total of 946 immune-related genes that were differentially expressed. Among them, five independent genes, including SHC1, WNT5A, NRP1, TGFA, and IL4R, were significantly associated with survival and used to construct the immune-related prognostic differential gene signature (IRPDGs). Then the ccRCC patients were categorized into high-risk and low-risk subgroups based on the median risk score of the IRPDGs. IRPDGs subgroups displays distinct genomic and immunological characteristics. Known immunotherapy-related genes show different mutation burden, wherein the mutation rate of VHL was higher than 40% in the two IRPDGs subgroups, and SETD2 and BAP1 mutations differed most between two groups with higher frequency in the high-risk subgroup. Moreover, IRPDGs subgroups had different abundance in tumor-infiltrating immune cells (TIICs) with distinct immunotherapy efficacy. Plasma cells, regulatory cells (Tregs), follicular helper T cells (Tfh), and M0 macrophages were enriched in the high-risk group with a higher tumor immune dysfunction and rejection (TIDE) score. In contrast, the low-risk group had abundant M1 macrophages, mast cell resting and dendritic cell resting infiltrates with lower TIDE score and benefited more from immune checkpoint inhibitors (ICI) treatment. Compared with other biomarkers, such as TIDE and tumor inflammatory signatures (TIS), IRPDGs demonstrated to be a better biomarker for assessing the prognosis of ccRCC and the efficacy of ICI treatment with the promise in screening precise patients for specific immunotherapies.
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http://dx.doi.org/10.3389/fimmu.2022.890150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9171405PMC
May 2022

Precision environmental health monitoring by longitudinal exposome and multi-omics profiling.

Genome Res 2022 Jun 6;32(6):1199-1214. Epub 2022 Jun 6.

Department of Genetics, Stanford University School of Medicine, Stanford, California 94304, USA.

Conventional environmental health studies have primarily focused on limited environmental stressors at the population level, which lacks the power to dissect the complexity and heterogeneity of individualized environmental exposures. Here, as a pilot case study, we integrated deep-profiled longitudinal personal exposome and internal multi-omics to systematically investigate how the exposome shapes a single individual's phenome. We annotated thousands of chemical and biological components in the personal exposome cloud and found they were significantly correlated with thousands of internal biomolecules, which was further cross-validated using corresponding clinical data. Our results showed that agrochemicals and fungi predominated in the highly diverse and dynamic personal exposome, and the biomolecules and pathways related to the individual's immune system, kidney, and liver were highly associated with the personal external exposome. Overall, this data-driven longitudinal monitoring study shows the potential dynamic interactions between the personal exposome and internal multi-omics, as well as the impact of the exposome on precision health by producing abundant testable hypotheses.
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http://dx.doi.org/10.1101/gr.276521.121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9248886PMC
June 2022

Multiple optimizations of recombinant plasmid for improving expression of Hepatitis B core antigen in Escherichia coli.

Protein Expr Purif 2022 10 3;198:106127. Epub 2022 Jun 3.

YishengBio Co., Ltd., Beijing, 102629, China. Electronic address:

Hepatitis B core antigen (HBcAg) can self-assemble into virus-like particles (VLPs) when expressed in Escherichia coli. We optimized the different of the expression plasmid pBV220, including the ribosome bind site (RBS), spacer region, promoter and replication origin (ori), as well as the hbc gene dosage, to enhance HBcAg transcription and translation in E. coli. The optimized construct with a customized RBS6, 6 nt spacer, T7 promoter and pUCori significantly increased the levels of HBc36GFP fusion protein to 3.4-folds compared to the control. Thereafter, we substituted hbc36gfp gene with different copies of the hbc gene and tested the effects of gene dosage on HBcAg expression. The HBcAg-VLPs yield obtained using an engineered strain with three copies of hbc was 842.1 ± 46.8 μg/mL, which was 2.2-folds higher compared to that in the control strain. Thus, our study provides a simple and effective strategy for improving HBcAg expression in E. coli. Since the HBcAg-VLPs are promising carriers for presenting foreign antigen epitopes, an in vitro expression system that can generate high levels of HBcAg-VLPs can serve as a promising tool for developing novel HBV vaccines and drugs.
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http://dx.doi.org/10.1016/j.pep.2022.106127DOI Listing
October 2022

Impact of Adjuvant Chemotherapy on FIGO Stage I Ovarian Clear Cell Carcinoma: A Systematic Review and Meta-Analysis.

Front Oncol 2022 17;12:811638. Epub 2022 May 17.

Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetric and Gynecologic Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: Ovarian clear cell carcinoma (OCCC) is an uncommon subtype of epithelial ovarian carcinoma (EOC) that is often diagnosed at an earlier stage in younger women. It remains uncertain whether adjuvant chemotherapy improves the prognosis of patients with stage I OCCC.

Objective: This systematic review and meta-analysis aimed to assess the impact of adjuvant chemotherapy on survival in patients with stage I OCCC.

Search Strategy: Eligible studies were screened from PubMed, Web of Science, Embase, and the Cochrane Library up to October 10, 2021.

Selection Criteria: Studies that compared the oncological outcomes of adjuvant chemotherapy with observation were included.

Data Collection And Analysis: Six studies comprising a total of 4553 patients were enrolled in our study, of whom 3320 (72.9%) patients had undergone adjuvant chemotherapy and 1233 (27.1%) had not.

Main Results: The 5-year disease-free survival (DFS) and 5-year overall survival (OS) of stage I OCCC were 82.7% and 86.3%, respectively. In the overall population, adjuvant chemotherapy did not improve the 5-year DFS (83.2% vs 83.7%, OR 0.77, 95% CI 0.21-2.82, P=0.69) or 5-year OS (87.3% vs 83.6%, OR 1.30, 95% CI 0.86-1.98, P=0.22). Further subgroup analysis on stage IA/IB suggested that adjuvant chemotherapy did not impact 5-year DFS (OR 0.20, 95% CI 0.01-5.29, P=0.34) or 5-year OS (OR 1.52, 95% CI 0.78-2.98, P=0.22). For stage IC including 1798 patients, adjuvant chemotherapy revealed a significant survival benefit for 5-year OS (84.5% vs 83.3%, OR 1.44, 95% CI 1.08-1.94, P=0.01). Furthermore, the administration of adjuvant chemotherapy was found to be associated with a better 5-year OS (OR 4.98, 95% CI 1.12-22.22, P=0.04) in stage IC2/3. But no inferences regarding the effect of AC on stage IC2/3 can be made due to the limited size of the non-AC arm.

Conclusion: This study indicated that adjuvant chemotherapy did not improve the prognosis of stage IA and IB OCCC patients. However, for patients with stage IC, due to the retrospective, heterogenous and older data with limited sample size, the pooled results of our study should be interpreted with caution. More prospective studies on the role of adjuvant chemotherapy in stage I OCCC are warranted.

Systematic Review Registration: PROSPERO, CRD42021287749.
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http://dx.doi.org/10.3389/fonc.2022.811638DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9152288PMC
May 2022

Production of Gluconic Acid and Its Derivatives by Microbial Fermentation: Process Improvement Based on Integrated Routes.

Front Bioeng Biotechnol 2022 16;10:864787. Epub 2022 May 16.

School of Marine Science and Engineering, Qingdao Agricultural University, Qingdao, China.

Gluconic acid (GA) and its derivatives, as multifunctional biological chassis compounds, have been widely used in the food, medicine, textile, beverage and construction industries. For the past few decades, the favored production means of GA and its derivatives are microbial fermentation using various carbon sources containing glucose hydrolysates due to high-yield GA production and mature fermentation processes. Advancements in improving fermentation process are thriving which enable more efficient and economical industrial fermentation to produce GA and its derivatives, such as the replacement of carbon sources with agro-industrial byproducts and integrated routes involving genetically modified strains, cascade hydrolysis or micro- and nanofiltration in a membrane unit. These efforts pave the way for cheaper industrial fermentation process of GA and its derivatives, which would expand the application and widen the market of them. This review summarizes the recent advances, points out the existing challenges and provides an outlook on future development regarding the production of GA and its derivatives by microbial fermentation, aiming to promote the combination of innovative production of GA and its derivatives with industrial fermentation in practice.
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http://dx.doi.org/10.3389/fbioe.2022.864787DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9149244PMC
May 2022

Evaluation of physician experience in achieving non-perfused volume ratio of high-intensity focused ultrasound ablation for uterine fibroids: a multicentre study.

J Int Med Res 2022 May;50(5):3000605221102087

State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, China.

Objective: To evaluate the effect of different levels of physician experience on the high-intensity focused ultrasound (HIFU) ablation of uterine fibroids and to provide a reference for the use of non-perfused volume ratio (NPVR) standards during training.

Methods: This prospective multicentre study enrolled patients with uterine fibroids. The effect of the physician's level of experience on the outcomes under different NPVR standards and the learning curve of six centres without HIFU experience were analysed. The impact of patient demographic and clinical characteristics were also evaluated.

Results: A total of 1352 patients from 20 centres were included in the study. The median NPVRs were 92.00%, 88.10% and 92.86% in the no experience group, inexperienced group and experienced group, respectively. Posterior wall fibroids, lateral wall fibroids and fundus fibroids were inversely correlated with NPVR, while experienced physicians were positively correlated with NPVR. With NPVR ≥ 70% and NPVR ≥ 80% standards, physicians in the no experience group completed the learning curve on the 11th and 16th procedure, respectively. Physicians under a standard of an NPVR ≥ 90% did not complete the learning curve.

Conclusions: NPVR ≥ 80% is a standard that is worth using for HIFU treatment of uterine fibroids.
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http://dx.doi.org/10.1177/03000605221102087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9158416PMC
May 2022

A Novel Sandwich ELASA Based on Aptamer for Detection of Largemouth Bass Virus (LMBV).

Viruses 2022 04 30;14(5). Epub 2022 Apr 30.

College of Marine Sciences, South China Agricultural University, Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou 510642, China.

Largemouth bass virus (LMBV) is a major viral pathogen in largemouth bass culture, usually causing high mortality and heavy economic losses. Accurate and early detection of LMBV is crucial for diagnosis and control of the diseases caused by LMBV. Previously, we selected the specific aptamers, LA38 and LA13, targeting LMBV by systematic evolution of ligands by exponential enrichment (SELEX). In this study, we further generated truncated LA38 and LA13 (named as LA38s and LA13s) with high specificity and affinities and developed an aptamer-based sandwich enzyme-linked apta-sorbent assay (ELASA) for LMBV diagnosis. The sandwich ELASA showed high specificity and sensitivity for the LMBV detection, without cross reaction with other viruses. The detection limit of the ELASA was as low as 1.25 × 10 LMBV-infected cells, and the incubation time of the lysate and biotin labeled aptamer was as short as 10 min. The ELASA could still detect LMBV infection in spleen lysates at dilutions of 1/25, with good consistency of qRT-PCR. For the fish samples collected from the field, the sensitivity of ELASA was 13.3% less than PCR, but the ELASA was much more convenient and less time consuming. The procedure of ELASA mainly requires washing and incubation, with completion in approximately 4 h. The sandwich ELASA offers a useful tool to rapidly detect LMBV rapidly, contributing to control and prevention of LMBV infection.
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http://dx.doi.org/10.3390/v14050945DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9145880PMC
April 2022

Molecular diagnosis of adult patients with clinically unexplained hypokalemia without hypertension demonstrated a diagnostic yield of 30.5.

Clin Genet 2022 Sep 2;102(3):228-233. Epub 2022 Jun 2.

Department of Endocrinology and Metabolism, West China Hospital of Sichuan University, Chengdu, China.

Hypokalemia is a common disorder in clinical settings; however, nonmolecular diagnostic testing cannot explain some causes of hypokalemia. To determine the etiology of clinically unexplained hypokalemia without hypertension (CUHypoNH) and to obtain a diagnostic yield of monogenic hypokalemia without hypertension in adults (MHNHA), we enrolled 82 patients with CUHypoNH for whole-exome sequencing or targeted gene sequencing of genes associated with 4000 monogenic disorders. Through molecular diagnosis, 25 patients were diagnosed with monogenic hypokalemia, and a diagnostic yield of 30.5% was obtained. Among patients with MHNHA, 18 patients (18/82, 22.0% and 72% of MHNHA) with Gitelman syndrome accounted for the largest proportion. Among the 29 diagnostic variants found, eight mutations have not been reported previously; these include three point mutations, one frameshift mutation, and four exon deletions. Based on the clinical presentation of patients with CUHypoNH, the diagnostic yield of monogenic hypokalemia was the highest for chronic asymptomatic hypokalemia (8/11, 72.7%). Twenty-one patients had concomitant hypomagnesemia, when accompanied with hypocalciuria, the molecular diagnostic yield of Gitelman syndrome increased to 88.2%. Overall, this study on hospitalized adult patients explored the etiology of CUHypoNH using high-throughput sequencing. Molecular diagnosis of CUHypoNH is clinically significant in guiding precision treatment and improving disease prognosis.
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http://dx.doi.org/10.1111/cge.14168DOI Listing
September 2022

Mutations in DNA binding domain of p53 impede RSL1D1-p53 interaction to escape from degradation in human colorectal cancer cells.

Exp Cell Res 2022 Aug 18;417(1):113211. Epub 2022 May 18.

College of Bioscience and Biotechnology, Yangzhou University, Yangzhou, Jiangsu, 225009, China; Joint International Research Laboratory of Agriculture & Agri-Product Safety, The Ministry of Education of China, Yangzhou University, Yangzhou, Jiangsu, 225009, China; Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agrifood Safety and Quality, The Ministry of Agriculture of China, Yangzhou University (26116120), Yangzhou, Jiangsu, 225009, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu, 225009, China. Electronic address:

Different from the nucleolus-specific localization in some types of cancer cells, ribosomal L1 domain-containing protein 1 (RSL1D1) distributes throughout the nucleus in human colorectal cancer (CRC) cells. RSL1D1 directly interacts with DNA binding domain (aa 93-292) of wild-type p53 (p53-WT) and thereby recruits p53 to HDM2. The ensuing formation of RSL1D1/HDM2/p53 complex enhances p53 ubiquitination and decreases the protein level of p53 in CRC cells. In this study, we investigated the interaction between RSL1D1 and mutant p53 proteins. We first corroborated that aa 93-224 of p53 is a more precise domain for RSL1D1 binding and mutation in either aa 93-224 or aa 225-292 domain of p53 affects RSL1D1-p53 interaction. R175H mutated p53 does not interact with RSL1D1, whereas R273H mutated p53 still can bind to RSL1D1 but showing a remarkably decreased affinity than p53-WT. Although p53-R273H retains a weakened binding affinity with RSL1D1, it can hardly be recruited to HDM2 by RSL1D1 in HCT116 CRC cells. Accordingly, RSL1D1 loses its capacity to negatively regulate either R175H or R273H p53 mutant via directly interaction in HCT116 cells, thereby facilitating p53 mutants to accumulate and gain oncogenic function. Our findings help explain why mutant p53 proteins are more stable than p53-WT in CRC cells.
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http://dx.doi.org/10.1016/j.yexcr.2022.113211DOI Listing
August 2022

Molecular cytogenetic characterization of 16p11.2 microdeletions with diverse prenatal phenotypes: Four cases report and literature review.

Taiwan J Obstet Gynecol 2022 May;61(3):544-550

Center for Reproductive Medicine and Center for Prenatal Diagnosis, First Hospital, Jilin University, Changchun, 130021, China; Jilin Engineering Research Center for Reproductive Medicine and Genetics, Jilin University, Changchun, 130021, China. Electronic address:

Objective: Chromosome 16p11.2 deletions have been recognized as a genetic disorder with well-described postnatal phenotypes. However, the prenatal manifestations are atypical for lacking of enough evidence.

Case Report: Four pregnant women underwent amniocentesis for cytogenetic analysis and chromosomal microarray analysis (CMA) because of various indications for prenatal diagnosis: prenatal ultrasound abnormalities (cases 1, 2 and 4) and the childbearing history of cerebral palsy child (case 3). No overlapping phenotypes were observed in cases 1, 2 and 4, which might indicate phenotypic diversities in prenatal phenotypes for 16p11.2 microdeletion. All four fetuses showed normal karyotypic results while CMA identified 0.303-0.916 Mb microdeletions of 16p11.2, encompassing BP2-BP3 and BP4-BP5 regions separately. According to the parental CMA verification, case 1 carried a maternal inherited duplication in the region of Xp22.33 and a de novo deletion in the region of Xp21.1. All parents opted for the termination of pregnancies based upon genetic counselling.

Conclusion: Our findings enriched the intrauterine phenotypic features of 16p11.2 microdeletions, which would be beneficial for genetic counselling in clinic. In addition, preimplantation genetic testing was recognized as a first-tier approach for such carriers if they intended to conceive again.
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http://dx.doi.org/10.1016/j.tjog.2022.03.027DOI Listing
May 2022
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