Publications by authors named "Yan Huang"

3,081 Publications

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Draft Genome Sequence of the Extremely Haloalkaliphilic and Homoacetic Bacterium Natroniella acetigena Z-7937.

Microbiol Resour Announc 2022 Aug 11:e0047222. Epub 2022 Aug 11.

Graduate School of Agriculture, Hokkaido University, Sapporo, Japan.

Natroniella acetigena Z-7937 (= DSM 9952) is a heterotrophic homoacetogenic natronophile. The draft genome sequence is 2.6 Mb in 116 contigs, with a G+C content of 34.1%.
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http://dx.doi.org/10.1128/mra.00472-22DOI Listing
August 2022

First-in-human phase I study of TQ-B3139 (CT-711) in advanced non-small cell lung cancer patients with ALK and ROS1 rearrangements.

Eur J Cancer 2022 Aug 5;173:238-249. Epub 2022 Aug 5.

Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. Electronic address:

Background: TQ-B3139 is a novel ALK tyrosine kinase inhibitor (TKI) against a broad range of ALK mutations. The aim of this first-in-human phase I trial was to investigate the safety, tolerability, pharmacokinetics, and clinical efficacy of TQ-B3139 in ALK or ROS1 positive advanced NSCLC patients.

Methods: Following a 3 + 3 design, patients received escalating daily dose of TQ-B3139 (50-800 mg) continuously in 28-day cycles. Expansion stage started at dose of 200 mg twice daily (BID). The primary objectives were the safety, dose-limited toxicities (DLT) and recommended phase II dose (RP2D); secondary objectives included pharmacokinetics and antitumor activity. Non-obligatory tumor samples at baseline were collected and sequenced.

Results: The study enrolled 63 patients. Fifty-nine (93.4%) patients experienced treatment-related adverse events (TRAEs), mostly grade 1-2 vomiting (79.3%), diarrhea (76.1%) or nausea (68.2%). 1 (1/6) DLT occurred at 600 mg BID and 1 (1/3) at 800 mg BID. Based on safety and pharmacokinetics data, the RP2D was selected as 600 mg BID. At a dose level ≥200 mg BID, the overall response rate (ORR) was 76.7% (33/43), and the median progression free survival (mPFS) was 25.2 months (95%CI 11.9-NR) for TKI-naive patients. For TKI-treated patients, the ORR was 37.5% (6/16), and the mPFS was 5.4 months (95%CI 3.6-9.1). The ORR was 66.7% (2/3) in patients with ROS1 fusion at dose level ≥200 mg BID. In patients with measurable brain metastases, the intracranial ORR was 70% (7/10), with median intracranial PFS of 15.9 months. In TKI-treated patients, variant 3 and TP53 alteration were associated with poor PFS.

Conclusions: TQ-B3139 was well-tolerated and exhibited promising anti-tumor activities in patients with ALK and ROS1 positive advanced NSCLC.

Clinical Trial Number: NCT03099330.
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http://dx.doi.org/10.1016/j.ejca.2022.06.037DOI Listing
August 2022

Efficacy of Low Molecular Weight Heparin in Preventing Perinatal Venous Thrombosis: A Meta-Analysis.

Comput Math Methods Med 2022 26;2022:1248577. Epub 2022 Jul 26.

Department of Pharmacy, Hainan Women and Children's Medical Center, Haikou 570216, China.

Background: There have been controversies about the preventive effect of low molecular weight heparin (LMWH) on venous thrombosis (VT) in the perinatal period. This study is aimed at exploring the effectiveness of LMWH in preventing perinatal VT through meta-analysis.

Methods: Databases such as CNKI, China Biology Medicine disc (CBMdisc), Wanfang, PubMed, MEDLINE, Embase, and Central were searched. Inclusion criteria were as follows: (1) subjects: women at high risk of perinatal VT; (2) experimental group and control group; (3) intervention measures: the experimental group was given LMWH, while the control group was given placebo or standard heparin or physical therapy; (4) outcomes: perinatal VT events or bleeding events; and (5) randomized controlled trials (RCTs). Jadad scale was used to evaluate the literature quality. The Mantel-Haenszel method was used to calculate the odds ratio (OR) and 95% confidence interval (CI). The chi-square test was used to analyze the heterogeneity of the included literature. Subgroup analysis was used to explore the source of heterogeneity. Publication bias was evaluated via funnel plot and Egger test.

Results: The incidence of perinatal VT in the LMWH group was lower than that in the control group (OR = 0.16, 95% CI (0.08, 0.32), < 0.00001). There was no heterogeneity among literatures ( = 0.77, = 0%) and no publication bias. The incidence of postpartum VT in the LMWH group was lower than that in the control group (OR = 0.14, 95% CI (0.07, 0.30), < 0.00001). There was no heterogeneity among literatures ( = 0.69, = 0%) and no publication bias. The incidence of perinatal bleeding in the LMWH group was higher than in the control group (OR = 1.72, 95% CI (1.06, 2.77), = 0.03). There was no heterogeneity among literatures ( = 0.25, = 26%) and no publication bias.

Conclusion: LMWH can reduce the incidence of perinatal VT in high-risk women but increase the risk of bleeding. The use of LMWH to prevent perinatal VT should be closely monitored.
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http://dx.doi.org/10.1155/2022/1248577DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9345706PMC
August 2022

Chinese contribution to , , , and from 2011 to 2020: a 10-year bibliometric study.

Ann Transl Med 2022 May;10(9):505

Department of Cardiac Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.

Background: (), , (), and () are collectively known as "the Top Four Medical Journals (TFMJ)" in China. Through the analysis of Chinese scholars' publications in the TFMJ in the recent 10 years, this study aimed to clarify the current situation of high-quality medical research conducted by Chinese scholars and institutions.

Methods: Data were retrieved and downloaded manually from PubMed (2011-2020). Information on the publication year, journal, author, affiliation, and citation, etc. were extracted and analyzed using R software.

Results: A total of 761 articles were involved in the final analysis. The number of articles published by Chinese scholars in the TFMJ was 135/29,942 (0.45%) in , 124/14,033 (0.88%) in , 314/16,117 (1.94%) in , and 188/15,242 (1.23%) in (P<0.001). Besides, the letter was the main research type, which was up to 44.54%, and the original research only accounted for 17.47%. The most popular subspecialty and subject were infectious diseases and COVID-19, respectively. The most productive researcher was Chen Wang, and Bin Cao was the most cited Chinese scholar. The most productive institute was Chinese Academy of Medical Sciences and Peking Union Medical College. The most cited study was "Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China".

Conclusions: The presence of Chinese scholars in the TFMJ has grown, but there is still much room to improve. A Matthew effect in China's high-level scientific research was demonstrated.
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http://dx.doi.org/10.21037/atm-21-6793DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9347039PMC
May 2022

Sarcopenia defined by skeletal muscle mass index at the third lumbar vertebra is a prognostic factor for extensive-stage small cell lung cancer patients: a retrospective study.

J Thorac Dis 2022 Jul;14(7):2645-2651

Department of Medical Oncology, Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China.

Background: Small cell lung cancer (SCLC) is one of the most aggressive types of lung cancer and reliable indicators are needed for improved patient management. The evaluation of skeletal muscle index of the third lumbar vertebra (L3MI) based on computed tomography (CT) is used to estimate patient prognosis in multiple cancers. However, its function in extensive-stage SCLC remains controversial. Considering that the maintenance of muscle mass may affect the survival of cancer patients. Herein, a retrospective study was conducted to investigate whether sarcopenia defined by skeletal muscle mass index at the third lumbar vertebra is a prognostic factor in extensive-stage SCLC cancer patients.

Methods: This retrospective analysis included extensive-stage SCLC patients diagnosed at the Sun Yat-sen University Cancer Center from January 2009 to March 2017 with platinum-based chemotherapy. Clinical data were collated for further examination, and CT or positron emission tomography (PET)/CT datasets were analyzed for body mass index (BMI) and L3MI. Follow-up data were collected by contacting patients or their families. Overall survival (OS) was defined as the interval between the date of treatment started and the date of death or censoring. The Kaplan-Meier product limit method and log-rank tests were used to assess differences in OS between the high L3MI and low L3MI groups. Cox regression analysis was used to identify independent factors of OS.

Results: For the 139 extensive-stage SCLC patients, the median follow-up time was 26.1 months (range, 0.4 to 79.4 months). The median OS was 9.5 months. There were no differences in age, inflammatory factors, nor progression after first-line treatment between the high L3MI and low L3MI groups. Kaplan-Meier analysis showed that the OS of the high L3MI group was significantly longer than that of the low L3MI group (14.045 9.985 months; P=0.007), and multivariate analysis identified high L3MI to be an independent prognostic factor for predicting longer OS in extensive-stage SCLC patients [hazard ratio (HR), 0.623; 95% confidence interval (CI), 0.405-0.960; P=0.032].

Conclusions: Sarcopenia defined by L3MI is a prognostic factor for extensive-stage SCLC patients and early intervention of muscle mass maintaining may achieve better cancer management.
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http://dx.doi.org/10.21037/jtd-22-782DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9344420PMC
July 2022

Paclitaxel exposure-toxicity analysis reveals a pharmacokinetic determinant for dose-limiting neutropenia in East-Asian solid tumor patients: results from two prospective, phase II studies.

Cancer Chemother Pharmacol 2022 Aug 3. Epub 2022 Aug 3.

Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, No. 651 East Dongfeng Road, Guangzhou, 510060, China.

Purpose: The time of a paclitaxel (PTX) concentration remains above 0.05 μM (Tc > 0.05) has been associated with PTX-induced adverse effects in Caucasians, while limited studies were reported in Asians. This study was aimed to explore the characteristics of Tc > 0.05 and the relationship between PTX exposure and toxicity in East-Asian patients.

Methods: This study was based on two prospective phase II clinical trials and patients with advanced nasopharyngeal cancer (NPC) and non-small cell lung cancer (NSCLC) who were naïve to PTX were included independently. Eligible patients receive PTX (175 mg/m) and carboplatin (AUC = 5) treatment every 3 weeks. PTX pharmacokinetic analysis was accessed. The relationship between PTX exposure and toxicities after first cycle as well as clinical efficacy was evaluated.

Results: A total of 93 NPC and 40 NSCLC patients were enrolled. PTX exposure was consistent in two trials with average Tc > 0.05 duration of 38.8 h and 38.4 h, respectively. Average Tc > 0.05 in patients with grade 3/4 neutropenia was significantly higher than those without severe neutropenia in NPC patients (P = 0.003) and NSCLC patients (P = 0.007). Cut-off value of Tc > 0.05 were identified from the NPC cohort and then verified in the NSCLC cohort, dividing patients into high exposure Tc > 0.05 group (> 39 h) and low exposure group (≤ 39 h). Incidence of grade 3/4 neutropenia were significantly higher in the high exposure group in NPC cohort (43.3% vs 10.0%, P < 0.001) and NSCLC cohort (42.1% vs 9.5%, P = 0.028). No significant relationship between Tc > 0.05 and efficacy were observed.

Conclusion: Patients with PTX Tc > 0.05 duration above 39 h experience more severe neutropenia than those under 39 h. Prospective studies are needed to verify this threshold.
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http://dx.doi.org/10.1007/s00280-022-04456-wDOI Listing
August 2022

Effect of light-emitting diodes with different color rendering indexes on the ocular tissues of rat.

Int J Ophthalmol 2022 18;15(7):1035-1043. Epub 2022 Jul 18.

Department of Ophthalmology and Optometry, Fujian Medical University, Fuzhou 350004, Fujian Province, China.

Aim: To compare the damage of light-emitting diodes (LEDs) with different color rendering indexes (CRIs) to the ocular surface and retina of rats.

Methods: Totally 20 Sprague-Dawley (SD) rats were randomly divided into four groups: the first group was normal control group without any intervention, other three groups were exposed by LEDs with low (LED-L), medium (LED-M), and high (LED-H) CRI respectively for 12h a day, continuously for 4wk. The changes in tear secretion (Schirmer I test, SIt), tear film break-up time (BUT), and corneal fluorescein sodium staining (CFS) scores were compared at different times (1d before experiment, 2 and 4wk after the experiment). The histopathological changes of rat lacrimal gland and retina were observed at 4wk, and the expressions of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in lacrimal gland were detected by immunofluorescence method.

Results: With the increase of light exposed time, the CFS value of each light exposed group continued to increase, and the BUT and SIt scores continued to decrease, which were different from the control group, and the differences between the light exposed groups were statistically significant. Hematoxylin-eosin (HE) results showed that the lacrimal glands of each exposed group were seen varying degrees of acinar atrophy, vacuole distribution, increasing of eosinophil granules, ; the retina showed obvious reduction of photoreceptor cell layer and changes in retinal thickness; LED-L group has the most significant change in all tests. Immunofluorescence suggested that the positive expressions of TNF-α and IL-6 in the lacrimal glands of each exposed group were higher than those of the control group.

Conclusion: LED exposure for 4wk can cause the pathological changes of lacrimal gland and retina of rats, and increase the expression of TNF-α and IL-6 in lacrimal gland, the degree of damage is negatively correlated with the CRI.
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http://dx.doi.org/10.18240/ijo.2022.07.01DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9318091PMC
July 2022

Oncologic Safety and Efficacy of Cell-Assisted Lipotransfer for Breast Reconstruction in a Murine Model of Residual Breast Cancer.

Aesthetic Plast Surg 2022 Aug 2. Epub 2022 Aug 2.

Department of Plastic and Reconstructive Surgery, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Korea.

Background: Cell-assisted lipotransfer (CAL) is a novel technique for fat grafting that combines the grafting of autologous fat and adipose-derived stromal cells (ASCs) to enhance fat graft retention; however, its oncologic safety is controversial.

Methods: Herein, we investigated the oncologic safety of CAL for breast reconstruction using a murine model of residual breast cancer. Various concentrations of 4T1 cells (murine breast cancer cells) were injected into female mastectomized BALB/c mice to determine the appropriate concentration for injection. One week after injection, mice were divided into control (100 μL fat), low CAL (2.5 × 10 ASCs/100 μL fat), and high CAL (1.0 × 10 ASCs/100 μL fat) groups, and fat grafting was performed. The injection of 5.0 × 10 4T1 cells was appropriate to produce a murine model of residual breast cancer.

Results: The weight of the fat tumor mass was significantly higher in the high CAL group than in the other groups (p < 0.05). However, the estimated tumor weight was not significantly different between the groups. Additionally, the fat graft survival rate was significantly higher in the high CAL group than in the control and low CAL groups (p < 0.05). No significant difference was noted in the percentage of Ki-67-positive cells, suggesting that tumor proliferation was not significantly different between the groups.

Conclusion: In summary, CAL significantly improved fat graft survival without affecting tumor size and proliferation in a murine model of residual breast cancer. These results highlight the oncologic safety of CAL for breast reconstruction.

No Level Assigned: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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http://dx.doi.org/10.1007/s00266-022-03021-3DOI Listing
August 2022

Draft Genome Sequence of the Alkaliphilic, Lithoautotrophic Homoacetogen Fuchsiella alkaliacetigena Z-7100.

Microbiol Resour Announc 2022 Aug 1:e0047122. Epub 2022 Aug 1.

Graduate School of Agriculture, Hokkaido University, Sapporo, Japan.

Fuchsiella alkaliacetigena is a spore-forming, alkaliphilic hydrogentrophic homoacetogen that was isolated from the soda lake Lake Tanatar III in Russia. The genome of the type strain Z-7100 (= DSM 24880) is 2.9 Mb, with a G+C content of 36.2%.
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http://dx.doi.org/10.1128/mra.00471-22DOI Listing
August 2022

Imbalanced T-Cell Subsets May Facilitate the Occurrence of Osteonecrosis of the Femoral Head.

J Inflamm Res 2022 22;15:4159-4169. Epub 2022 Jul 22.

Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, People's Republic of China.

Background: Osteonecrosis of the femoral head (ONFH) is a complex disease resulting in degeneration of the hip joint. The pathogenesis of ONFH is largely unknown, but alterations in immunological factors have been proposed to play a role.

Methods: We included 109 patients with ONFH and 109 age-, sex-, and body mass index-matched healthy controls in this study. The percentage of circulating CD3, CD4, and CD8 lymphocytes among the total lymphocytes was identified by flow cytometry and compared between the cases and controls. Subgroup analysis within each etiological group and correlation analysis of T-cell subset levels with disease duration were performed. Furthermore, we compared the expression patterns of CD4, RANKL, and FoxP3 in the femoral head of healthy and glucocorticoid (GC)-treated ONFH rats.

Results: The results showed that CD3 and CD4 T-cell counts and the CD4/CD8 ratio were significantly higher in patients with ONFH and that CD3 lymphocyte levels were negatively correlated with disease duration. The CD4 T-cell levels and CD4/CD8 ratios in the GC-ONFH etiological group were lower than those in the idiopathic-, traumatic-, and alcoholic-ONFH groups, while the CD8 T-cell levels were higher. Furthermore, the CD3, CD4, and CD8 T-cell counts and the CD4/CD8 ratio were higher in the GC-ONFH group than in the control group. Finally, we observed diminished levels of FoxP3/CD4 double-positive T regulatory cells and increased RANKL T-cell levels in the bone marrow of the femoral head in GC-ONFH rats.

Conclusion: The imbalance of T-cell subsets might be involved in the pathophysiological process of ONFH, and diminished CD4/FoxP3 T regulatory cells may be associated with increased RANKL T cells in the bone marrow of the femoral head in GC-ONFH, which may facilitate bone resorption and collapse of the femoral head.

Trial Registration: This study was registered in the Chinese Clinical Trial Registry (Registration number: ChiCTR2100042642).
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http://dx.doi.org/10.2147/JIR.S367214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9328079PMC
July 2022

Three-dimensional MoS-graphene aerogel nanocomposites for electrochemical sensing of quercetin.

Mikrochim Acta 2022 07 29;189(8):299. Epub 2022 Jul 29.

School of Chemistry and Chemical Engineering, Shandong University of Technology, Zibo, 255049, People's Republic of China.

A facile and novel electrochemical sensing platform is reported for quercetin determination with MoS nanoflowers-3D graphene aerogel (3D MoS-GA) nanocomposite as signal amplified material. The 3D MoS-GA nanocomposite was synthesized through a two-step hydrothermal method, in which MoS nanoflowers were prepared in advance. Characterizations of 3D MoS-GA were performed by scanning electron microscopy, transmission electron microscopy, Raman spectroscopy, X-ray diffraction, and X-ray photoelectron spectroscopy. The 3D MoS-GA-modified glassy carbon electrode (3D MoS-GA/GCE) was used to investigate the electrochemical behaviors of quercetin with electrochemical parameters calculated, reaction mechanism discussed, and experimental conditions optimized. Notably, the redox peak current densities of quercetin on 3D MoS-GA/GCE raised 5.14 and 6.40 times compared with those on a bare GCE. Furthermore, a novel electroanalytical approach was proposed for the sensitive determination of quercetin within the concentration range 0.01 ~ 5.0 μmol/L, accompanied by a low detection limit of 0.0026 μmol/L (at a working potential of 0.38 V vs. Ag/AgCl). The recovery for practical sample analysis ranges from 97.0 to 105%, and the relative standard deviation is less than 4.2%. This established method shows reliable performance in determination of quercetin in tablets and urine samples.
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http://dx.doi.org/10.1007/s00604-022-05336-zDOI Listing
July 2022

Hypothetical bromodomain-containing protein 5 is required for the growth of Toxoplasma gondii.

Vet Parasitol 2022 Jul 22;309:109767. Epub 2022 Jul 22.

Key Laboratory of Animal Parasitology of Ministry of Agriculture, Laboratory of Quality and Safety Risk Assessment for Animal Products on Biohazards (Shanghai) of Ministry of Agriculture, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China. Electronic address:

Bromodomain (BRD) is a highly conserved structural module domain, found in various proteins, including chromatin-related proteins, nucleus acetyltransferases, and transcription-associated proteins. Toxoplasma gondii, a zoonotic protozoan, encodes at least 12 predicted BRD-containing proteins (BDPs). Here, we investigated the subcellular location and regulatory role of a hypothetical protein BDP that we named TgBDP5. The BRD of TgBDP5 did not contain the conserved Asn and Tyr residues required for acetyl-lysine recognition. TgBDP5 localized in the nucleus of the parasite and remained unchanged during parasite replication. Conditional ablation of TgBDP5 through an auxin-inducible degron-based knockdown strategy caused a growth defect in parasite replication. Depletion of TgBDP5 led to changes in the expression level of 179 genes, suggesting it as an important target for drugs acting against T. gondii.
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http://dx.doi.org/10.1016/j.vetpar.2022.109767DOI Listing
July 2022

Caveolin-1 Alleviates Acetaminophen-Induced Hepatotoxicity in Alcoholic Fatty Liver Disease by Regulating the Ang II/EGFR/ERK Axis.

Int J Mol Sci 2022 Jul 8;23(14). Epub 2022 Jul 8.

Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei 230032, China.

Acetaminophen (APAP) is a widely used antipyretic analgesic which can lead to acute liver failure after overdoses. Chronic alcoholic fatty liver disease (AFLD) appears to enhance the risk and severity of APAP-induced liver injury, and the level of angiotensin II (Ang II) increased sharply at the same time. However, the underlying mechanisms remain unclear. Caveolin-1 (CAV1) has been proven to have a protective effect on AFLD. This study aimed to examine whether CAV1 can protect the APAP-induced hepatotoxicity of AFLD by affecting Ang II or its related targets. In vivo, the AFLD model was established according to the chronic-plus-binge ethanol model. Liver injury and hepatic lipid accumulation level were determined. The levels of Angiotensin converting enzyme 2 (ACE2), Ang II, CAV1, and other relevant proteins were evaluated by western blotting. In vitro, L02 cells were treated with alcohol and oleic acid mixture and APAP. CAV1 and ACE2 expression was downregulated in APAP-treated AFLD mice compared to APAP-treated mice. The overexpression of CAV1 in mice and L02 cells alleviated APAP-induced hepatotoxicity in AFLD and downregulated Ang II, p-EGFR/EGFR and P-ERK/ERK expression. Immunofluorescence experiments revealed interactions between CAV1, Ang II, and EGFR. The application of losartan (an Ang II receptor antagonist) and PD98059 (an ERK1/2 inhibitor) alleviated APAP-induced hepatotoxicity in AFLD. In conclusion, our findings verified that CAV1 alleviates APAP-aggravated hepatotoxicity in AFLD by downregulating the Ang II /EGFR/ERK axis, which could be a novel therapeutic target for its prevention or treatment.
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http://dx.doi.org/10.3390/ijms23147587DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9317714PMC
July 2022

Improvement of irradiation-induced fibroblast damage by α2-macroglobulin through alleviating mitochondrial dysfunction.

Pharm Biol 2022 Dec;60(1):1365-1373

NMPA Key Laboratory for Quality Control of Blood Products, Institute of Health Service and Transfusion Medicine, Academy of Military Medical Sciences, Beijing, PR China.

Context: α2-Macroglobulin (α2-M) is believed to be a potential anti-irradiation agent, but related mechanisms remains unclear.

Objective: We investigated the irradiation protective effect of α2-M.

Materials And Methods: A total of 10 Gy dose of irradiation was used to damage human skin fibroblasts. The influence of α2-M (100 µg/mL) on the proliferation, migration, invasion and apoptosis of fibroblasts was observed using Cell Counting Kit-8 (CCK8), wound healing, transwell, and flow cytometry. Malondialdehyde, superoxide dismutase and catalase was measured using related ELISA kits. The levels of mitochondrial membrane potential and calcium were detected using flow cytometry. The expression of transient receptor potential melastatin 2 (TRPM2) was investigated through western blotting and immunofluorescence staining.

Results: High purity of α2-M was isolated from Cohn fraction IV. α2-M significantly increased cell proliferation, migration, invasion, but suppressed cell apoptosis after irradiation. The promotion of cell proliferation, migration and invasion by α2-M exceeded over 50% compared group irradiation. The increased cell ratio in the S phase and decreased cell ratio in the G2 phase induced by irradiation were remarkably reversed by α2-M. α2-M markedly suppressed the increased oxidative stress level caused by irradiation. The mitochondrial damage induced by irradiation was improved by α2-M through inhibiting mitochondrial membrane potential loss, calcium and TRPM2 expression.

Discussion And Conclusions: α2-M significantly promoted the decreased fibroblast viability and improved the mitochondria dysfunction caused by irradiation. α2-M might present anti-radiation effect through alleviating mitochondrial dysfunction caused by irradiation. This study could provide a novel understanding about the improvement of α2-M on irradiation-induced injury.
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http://dx.doi.org/10.1080/13880209.2022.2096077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9336502PMC
December 2022

Hepatitis B Virus Reactivation Increased the Risk of Developing Hepatic Failure and Mortality in Cirrhosis With Acute Exacerbation.

Front Microbiol 2022 7;13:910549. Epub 2022 Jul 7.

Department of Infectious Diseases, Hubei Clinical Research Center for Precise Diagnosis and Therapy of Liver Cancer, Taihe Hospital, Hubei University of Medicine, Shiyan, China.

Background And Aims: Hepatitis B virus (HBV) reactivation is a serious condition and has been extensively described in chemotherapeutic immunosuppressive population. However, little is known about HBV reactivation in immunocompetent patients with chronic hepatitis B (CHB). In this study, we evaluated the prevalence and the clinical significance of HBV reactivation in CHB patients with acute exacerbations.

Method: Patients were screened from two prospective multicenter observational cohorts (CATCH-LIFE cohort). A total of 1,020 CHB patients with previous antiviral treatment history were included to assess the prevalence, risk factors, clinical characteristics of HBV reactivation, and its influence on the progression of chronic liver disease.

Results: The prevalence of HBV reactivation was 51.9% in CHB patients with acute exacerbations who had antiviral treatment history in our study. Among the 529 patients with HBV reactivation, 70.9% of them were triggered by discontinued antiviral treatment and 5.9% by nucleos(t)ide analogs (NUCs) resistance. The prevalence of antiviral treatment disruption and NUCs resistance in patients with HBV reactivation is much higher than that in the patients without (70.9% vs. 0.2%, and 5.9% vs. 0, respectively, both  < 0.001). Stratified and interaction analysis showed that HBV reactivation was correlated with high short-term mortality in cirrhosis subgroup (HR = 2.1,  < 0.001). Cirrhotic patients with HBV reactivation had a significantly higher proportion of developing hepatic failure (45.0% vs. 20.3%,  < 0.001), acute-on-chronic liver failure (ACLF; 31.4% vs. 21.8%,  = 0.005), and short-term death (14.0% vs. 5.9% for 28-day, and 23.3% vs. 12.4% for 90-day, both  < 0.001) than those without. HBV reactivation is an independent risk factor of 90-day mortality for cirrhosis patients (OR = 1.70,  = 0.005), as well as hepatic encephalopathy, ascites, and bacterial infection.

Conclusion: This study clearly demonstrated that there was a high prevalence of HBV reactivation in CHB patients, which was mainly triggered by discontinued antiviral treatment. The HBV reactivation strongly increased the risk of developing hepatic failure, ACLF and short-term death in HBV-related cirrhotic patients, which may suggest that HBV reactivation would be a new challenge in achieving the WHO target of 65% reduction in mortality from hepatitis B by 2030.
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http://dx.doi.org/10.3389/fmicb.2022.910549DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9300993PMC
July 2022

qHBsAg for the Identification of Liver Histological Abnormalities in HBeAg-Negative Chronic Hepatitis B Patients with Normal and Mildly Elevated ALT Levels.

Can J Gastroenterol Hepatol 2022 14;2022:8695196. Epub 2022 Jul 14.

Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.

Backgrounds: Noninvasive detection of histological abnormalities remains challenging in patients with HBeAg-negative chronic HBV infection with normal or mildly elevated levels of alanine aminotransferase (ALT). This study aimed to assess the utility of serum quantitative hepatitis B surface antigen (qHBsAg) in identifying significant histological lesions in this population.

Methods: This is a single-center study with retrospective analysis of 392 treatment-naive patients of HBeAg-negative chronic HBV infection with normal or mildly elevated levels of ALT.

Results: In this cohort, significant necroinflammation and fibrosis were found in 69.4% and 61.5% of patients, respectively. Patients with qHBsAg >1000 IU/mL ( = 236) had more hepatic inflammation of ≥2 (75.4% vs. 60.9%, < 0.01) or fibrosis ≥ 2 (66.1% vs. 54.5%, < 0.05) compared to those without ( = 156). Serum HBsAg (cutoff point = 1000 IU/mL), aspartate aminotransferase (AST) level (cutoff point = 25 IU/L), age (cutoff point = 40 years), and HBV family history were identified as independent predictors of significant histological abnormalities in multivariate logistic analysis.

Conclusions: A significantly higher proportion of patients with histological abnormalities were found in patients with qHBsAg >1000 IU/mL than those without. The qHBsAg level together with age, AST, and family history of HBV infection could be used as an algorithm to help noninvasive patient selection for antiviral therapy.
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http://dx.doi.org/10.1155/2022/8695196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9303505PMC
July 2022

The Role of ASIC1a in Inflammatory Immune Diseases: A Potential Therapeutic Target.

Front Pharmacol 2022 8;13:942209. Epub 2022 Jul 8.

Anhui Provincial Laboratory of Inflammatory and Immunity Disease, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, China.

It is acknowledged that chronic inflammation is associated with a rise in extracellular proton concentrations. The acid-sensing ion channel 1a (ASIC1a) belongs to the extracellular H-activated cation channel family. Recently, many studies have been conducted on ASIC1a and inflammatory immune diseases. Here, in this review, we will focus on the role of ASIC1a in several inflammatory immune diseases so as to provide new perspectives for clinical treatment.
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http://dx.doi.org/10.3389/fphar.2022.942209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9304623PMC
July 2022

Steamed and its Saponins Inhibit the Migration and Induce the Apoptosis of Neutrophils in a Zebrafish Tail-Fin Amputation Model.

Front Pharmacol 2022 7;13:946900. Epub 2022 Jul 7.

Leiden University-European Center for Chinese Medicine and Natural Compounds, Institute of Biology Leiden, Leiden University, Leiden, Netherlands.

(PN) is a Chinese medicinal herb that is traditionally used to treat inflammation and immune-related diseases. Its major active constituents are saponins, the types and levels of which can be changed in the process of steaming. These differences in saponins are causally relevant to the differences in the therapeutic efficacies of raw and steamed PN. In this study, we have prepared the extracts of steamed PN (SPNE) with 70% ethanol and investigated their immunomodulatory effect using a zebrafish tail-fin amputation model. A fingerprint-effect relationship analysis was performed to uncover active constituents of SPNE samples related to the inhibitory effect on neutrophil number. The results showed that SPNE significantly inhibited the neutrophil number at the amputation site of zebrafish larvae. And SPNE extracts steamed at higher temperatures and for longer time periods showed a stronger inhibitory effect. Ginsenosides Rh, Rk, Rh, 20()-Rg, and 20()-Rg, of which the levels were increased along with the duration of steaming, were found to be the major active constituents contributing to the neutrophil-inhibiting effect of SPNE. By additionally investigating the number of neutrophils in the entire tail of zebrafish larvae and performing TUNEL assays, we found that the decreased number of neutrophils at the amputation site was due to both the inhibition of their migration and apoptosis-inducing effects of the ginsenosides in SPNE on neutrophils. Among them, Rh and 20()-Rg did not affect the number of neutrophils at the entire tail, suggesting that they only inhibit the migration of neutrophils. In contrast, ginsenosides Rk, Rh, 20()-Rg, and SPNE did not only inhibit the migration of neutrophils but also promoted neutrophilic cell death. In conclusion, this study sheds light on how SPNE, in particular the ginsenosides it contains, plays a role in immune modulation.
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http://dx.doi.org/10.3389/fphar.2022.946900DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9302486PMC
July 2022

S-Doping Promotes Pyridine Nitrogen Conversion and Lattice Defects of Carbon Nitride to Enhance the Performance of Zn-Air Batteries.

ACS Appl Mater Interfaces 2022 Aug 22;14(30):34793-34801. Epub 2022 Jul 22.

State Key Laboratory of Advanced Welding and Joining, Harbin Institute of Technology (Shenzhen), Shenzhen 518055, China.

The efficient operation of Zn-air batteries (ZABs) requires highly active and stable reversible air catalysts. Studies have shown that heteroatom-doped carbonaceous nanomaterials are effective metal-free electrocatalysts for the oxygen evolution reaction (OER) and the oxygen reduction reaction (ORR). Herein, we design a facile and scalable catalyst doping scheme to manufacture S-doped carbon nitride (S-CN). Surprisingly, this metal-free catalyst exhibits excellent OER and ORR electrocatalytic activities in alkaline electrolytes, being comparable to those of commercial Pt/C. For the first time, it is proved by experiments that S doping can not only effectively increase the lattice defects of CN but also promote the conversion of pyrrolic nitrogen to pyridine nitrogen, thereby enhancing the bifunctional catalytic activity (OER and ORR). When the catalyst is used as an air electrode for rechargeable ZABs, its performance is obviously better than that provided by commercial Pt/C. Our findings and material design strategies are expected to provide new ideas for the synthesis of various high-performance carbon-based electrocatalysts.
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http://dx.doi.org/10.1021/acsami.2c09019DOI Listing
August 2022

The NPC Families Mediate BmNPV Entry.

Microbiol Spectr 2022 Jul 5:e0091722. Epub 2022 Jul 5.

State Key Laboratory of Silkworm Genome Biology, Southwest Universitygrid.263906.8, Chongqing, China.

Baculovirus is a powerful tool for biological control in agriculture and foreign gene expression and delivery in insect and mammalian cells. Baculovirus enters host cells by multiple endocytic pathways; however, the current understanding of the Bombyx mori nucleopolyhedrovirus (BmNPV) entry mechanism remains limited. Previous studies have identified NPC1 and NPC2 as important host factors for viral infection in insect cells, although their exact role in viral infection has not yet been determined. In this study, we demonstrate that the BmNPC1 protein is an important intracellular factor for BmNPV escape from the endosomal compartment, and the expression of BmNPC1 in Sf9 cells confers the virus the ability to enter into the nucleus of Sf9 cells. Additionally, the second luminal domain of BmNPC1 (BmNPC1-C) binds to the viral glycoprotein gp64, and preincubation of BmNPV with purified BmNPC1-C inhibits virus infection. Furthermore, knockout of the BmNPC2 protein results in reduced efficiency of viral fusion with the endosomal membrane, and BmNPC2 protein interacts directly with both viral envelope glycoprotein gp64 and the host BmNPC1 protein. BmNPC2 was found to be incorporated into progeny viral particles. Taken together, our results suggest that NPC2 protein incorporated into viral particles may facilitate viral infection through promoting the interaction of BmNPV and NPC1 in the endosome, thus enhancing viral fusion and escape from endosomes. These results, combined with those from previous studies, support that BmNPV hijacks two important cholesterol receptor members (NPC1 and NCP2) in the cholesterol intracellular transport pathway for viral entry into host cells. Baculovirus is an important biological factor for controlling insect populations and represents a powerful biological tool for gene delivery and expression. However, the host receptor of baculovirus is still unknown. In this study, we demonstrate that BmNPC1 protein is an important intracellular factor for BmNPV escape from the endosomal compartment, and the expression of BmNPC1 confers the ability of virus to enter into the host cell nucleus in nonpermissive Sf9 cells. BmNPC2 can bind to the virus and promote progeny virion infection through the NPC1-NPC2 endosome cholesterol transport pathway. We believe that our study on the BmNPV entry mechanism will further facilitate the application of baculovirus systems in eukaryotic gene delivery. Not only can the cholesterol transport pathway NPC1 protein be used by a variety of enveloped viruses, but the NPC2 protein can also be used by viruses to infect host cells. This will provide new insights into the study of enveloped virus infection mechanisms.
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http://dx.doi.org/10.1128/spectrum.00917-22DOI Listing
July 2022

Insights into male androgenetic alopecia using comparative transcriptome profiling: HIF-1 and Wnt/β-catenin signaling pathways.

Br J Dermatol 2022 Jul 21. Epub 2022 Jul 21.

Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China.

Background: The key pathophysiological changes in androgenetic alopecia (AGA) are limited to hair follicles (HFs) in frontal and vertex regions, except for the occipital region.

Objective: To identify biological differences among HF subpopulations.

Methods: Paired vertex and occipital HFs from 10 male AGA donors were collected for RNA-seq assay. Furthermore, hair follicle and cell experiments were conducted on the identified key genes to reveal their roles in AGA.

Results: Transcriptome profiles revealed that 506 mRNAs, 55 miRNAs, and 127 lncRNAs were differentially expressed (DE) in the AGA vertex HFs. Furthermore, pathway analysis of mRNAs and microRNAs revealed the involvement of the HIF-1, Wnt/β-catenin, and focal adhesion pathways. Differential expression of HIF-1 prolyl hydroxylase enzymes (EGLN1, EGLN3) and Wnt/β-catenin pathway inhibitors (PEDF, SFRP2) were experimentally validated. In vitro studies revealed that EGLN1/EGLN3/PEDF/SFRP2 reduction stimulated dermal papilla cell (DPC) proliferation. Ex vivo HF studies showed that EGLN1/EGLN3/PEDF downregulation promoted HF growth, postponed HF catagen transition, and prolonged the anagen stage, suggesting that these genes may be potentially utilized as therapeutic targets for AGA.

Conclusion: We characterized key transcriptome changes in male AGA HFs, and found that HIF-1 pathway-related genes (EGLN1/EGLN3) and Wnt pathway inhibitors (PEDF, SFRP2) may play important roles in AGA.
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http://dx.doi.org/10.1111/bjd.21783DOI Listing
July 2022

Evaluation of Clinical Outcomes of Icotinib in Patients With Clinically Diagnosed Advanced Lung Cancer With EGFR-Sensitizing Variants Assessed by Circulating Tumor DNA Testing: A Phase 2 Nonrandomized Clinical Trial.

JAMA Oncol 2022 Jul 21. Epub 2022 Jul 21.

State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Importance: The inability to obtain a pathological diagnosis in a certain proportion of patients with clinically diagnosed advanced lung cancer impedes precision treatment in clinical practice.

Objective: To evaluate the clinical outcome of first-line icotinib in patients with clinically diagnosed advanced lung cancer with unknown pathological status and positive epidermal growth factor receptor (EGFR)-sensitizing variants assessed by circulating tumor DNA (ctDNA).

Design, Setting, And Participants: The Efficiency of Icotinib in Plasma ctDNA EGFR Mutation-Positive Patients Diagnosed With Lung Cancer (CHALLENGE) trial is a prospective, multicentered, open-label, single-arm phase 2 nonrandomized clinical trial conducted between July 1, 2017, and July 31, 2019. Patients with systemic treatment-naive, clinically diagnosed advanced peripheral lung cancer, unknown pathological status, and positive pretreatment plasma EGFR-sensitizing variants were eligible. A total of 391 potentially eligible Chinese patients from 19 centers in China were screened for ctDNA EGFR variants by 3 independent detection platforms (Super amplification refractory mutation system [SuperARMS] polymerase chain reaction, droplet digital polymerase chain reaction, and next-generation sequencing), and those with EGFR variants tested by any platform were included. Analyses were conducted from September 9 to December 31, 2021.

Interventions: Enrolled patients were treated with oral icotinib tablets (125 mg 3 times daily) until disease progression, death, or treatment discontinuation due to various reasons, such as toxic effects and withdrawing consent.

Main Outcomes And Measures: The primary end point was objective response rate (ORR). The secondary end points included progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and the concordance among the 3 detection platforms.

Results: Of 116 included patients, 76 (65.5%) were female, and the median (range) age was 64 (37-85) years. The median (IQR) follow-up duration was 36.3 (30.2-40.7) months. The ORR was 52.6% (95% CI, 43.1%-61.9%). The median PFS and OS were 10.3 months (95% CI, 8.3-12.2) and 23.2 months (95% CI, 17.7-28.0), respectively, and the DCR was 84.5% (95% CI, 76.6%-90.5%). The concordance rate among the 3 detection platforms was 80.1% (313 of 391), and the clinical outcomes in patients identified as positive by any platform were comparable.

Conclusions And Relevance: This prospective phase 2 nonrandomized clinical trial suggests that for patients with clinically diagnosed advanced lung cancer with unknown pathological status, ctDNA-based EGFR genotyping could help decision-making in particular clinical situations, while still warranting future larger-scaled real-world exploration.

Trial Registration: ClinicalTrials.gov Identifier: NCT03346811.
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http://dx.doi.org/10.1001/jamaoncol.2022.2719DOI Listing
July 2022

Evaluation of droplet digital PCR rapid detection method and precise diagnosis and treatment for suspected sepsis (PROGRESS): a study protocol for a multi-center pragmatic randomized controlled trial.

BMC Infect Dis 2022 Jul 19;22(1):630. Epub 2022 Jul 19.

Department of Infectious Diseases, Xinhua Children's Hospital, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Sepsis is still a major public health concern and a medical emergency due to its high morbidity and mortality. Accurate and timely etiology diagnosis is crucial for sepsis management. As an emerging rapid and sensitive pathogen detection tool, digital droplet PCR (ddPCR) has shown promising potential in rapid identification of pathogens and antimicrobial resistance genes. However, the diagnostic value and clinical impact of ddPCR tests remains to be studied in patients with suspected sepsis. PROGRESS trial is aimed to evaluate the clinical effectiveness of a novel ddPCR assay compared with standard practice.

Methods: PROGRESS is a multicenter, open-label, pragmatic randomized controlled trial (pRCT) set in ten hospitals, including departments of infectious disease and intensive care units. In this study, a total of 2292 patients with suspected sepsis will be randomly assigned to two arms: the ddPCR group and the control group with a ratio of 3:1. The primary outcome is the diagnostic efficacy, that is, the sensitivity and specificity of the ddPCR assay compared with the synchronous blood culture. Secondary outcomes include the mortality rates and the mean Sequential Organ Failure Assessment (SOFA) score at follow-up time points, the length of stay in the hospital, the time to directed antimicrobial therapy, duration of broad-spectrum antibiotic use, and the EQ-5D-5L score on day 90.

Discussion: It is the first multicenter pragmatic RCT to explore the diagnostic efficacy and clinical impact of the ddPCR assay in patients with suspected sepsis, taking advantage of both RCT's ability to establish causality and the feasibility of pragmatic approaches in real-world studies (RWS). This trial will help us to get a comprehensive view of the assay's capacity for precise diagnosis and treatment of sepsis. It has the potential to monitor the pathogen load change and to guide the antimicrobial therapy, making a beneficial impact on the prognosis of sepsis patients.

Trial Registration: ClinicalTrial.gov, NCT05190861. Registered January 13, 2022-'Retrospectively registered', https://clinicaltrials.gov/ct2/show/NCT05190861 .
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http://dx.doi.org/10.1186/s12879-022-07557-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9295283PMC
July 2022

A hackable, multi-functional, and modular extrusion 3D printer for soft materials.

Sci Rep 2022 Jul 19;12(1):12294. Epub 2022 Jul 19.

Department of Engineering, University of Cambridge, Cambridge, UK.

Three-dimensional (3D) printing has emerged as a powerful tool for material, food, and life science research and development, where the technology's democratization necessitates the advancement of open-source platforms. Herein, we developed a hackable, multi-functional, and modular extrusion 3D printer for soft materials, nicknamed Printer.HM. Multi-printhead modules are established based on a robotic arm for heterogeneous construct creation, where ink printability can be tuned by accessories such as heating and UV modules. Software associated with Printer.HM were designed to accept geometry inputs including computer-aided design models, coordinates, equations, and pictures, to create prints of distinct characteristics. Printer.HM could further perform versatile operations, such as liquid dispensing, non-planar printing, and pick-and-place of meso-objects. By 'mix-and-match' software and hardware settings, Printer.HM demonstrated printing of pH-responsive soft actuators, plant-based functional hydrogels, and organ macro-anatomical models. Integrating affordability and open design, Printer.HM is envisaged to democratize 3D printing for soft, biological, and sustainable material architectures.
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http://dx.doi.org/10.1038/s41598-022-16008-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9296631PMC
July 2022

Novel compound heterozygous cadherin 3 mutations in hypotrichosis and juvenile macular dystrophy.

Chin Med J (Engl) 2022 Jul 20. Epub 2022 Jul 20.

Department of Dermatology, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, Zhejiang 310052, China.

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http://dx.doi.org/10.1097/CM9.0000000000002190DOI Listing
July 2022

Mulberry Leaf Flavonoids Inhibit Liver Inflammation in Type 2 Diabetes Rats by Regulating TLR4/MyD88/NF-B Signaling Pathway.

Evid Based Complement Alternat Med 2022 6;2022:3354062. Epub 2022 Jul 6.

Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China.

The incidence of liver-related complications in type 2 diabetes mellitus (T2DM) is rapidly increasing, which affects the physical and mental health of T2DM patients. Mulberry leaf flavonoids (MLF) were confirmed to have certain effects on lowering blood glucose and anti-inflammation. In this study, the high-fat diet (HFD) + STZ method was used to establish T2DM rat model and the MLF was administered by gavage for eight weeks. During the experiment, body weight and blood glucose level were measured at different time points. The pathological changes of rat liver were observed by H&E staining. The serum glucolipid metabolic indicators of serum, fasting insulin (FINS), and inflammatory factors levels were detected by ELISA. The expression levels of toll-like receptor 4 (TLR4), TNF receptor-associated factor 6 (TRAF6), myeloid differentiation factor 88 (MyD88), inhibitor of NF-B alpha (I), p-I, and nuclear factor kappa-B (NF-B)/p65 protein in liver tissue were measured by Western Blot. After 8 weeks' MLF treatment, the blood glucose of rats showed a downward trend; glycolipid metabolism level and insulin resistance were improved, which suggested that MLF could improve the disorder of glucose and lipid metabolism. The pathological damage and inflammation of the liver in T2DM rats were significantly improved, the levels of related serum inflammatory factors were reduced, and the expression of liver tissue-related proteins was downregulated. Our results indicated that MLF could reduce blood glucose and inhibit the development of liver inflammation. The mechanisms may be associated with the activation of TLR4/MyD88/NF-B signal pathway to reduce the levels of inflammatory factors in serum.
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http://dx.doi.org/10.1155/2022/3354062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9279020PMC
July 2022

Fibrillarin RNA methylase is an interacting protein of Cryptosporidium parvum calmodulin-like protein (CpCML).

Microb Pathog 2022 Jul 16;170:105679. Epub 2022 Jul 16.

Key Laboratory of Animal Parasitology of Ministry of Agriculture, Laboratory of Quality and Safety Risk Assessment for Animal Products on Biohazards (Shanghai) of Ministry of Agriculture, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, 200241, China. Electronic address:

Cryptosporidium parvum is an obligate protozoan parasite invading epithelial cells of small intestine of human and animals, and causing diarrheal disease. In apicomplexan parasites, calcium signaling can regulate many essential biological processes such as invasion and migration. As the main intracellular receptor for calcium ions, calmodulins control the activities of hundreds of enzymes and proteins. Calmodulin-like protein (CML) is an important member of the calmodulin family and may play a key role in C. parvum, however, the actual situation is still not clear. The present study aimed to identify the parasite interaction partner proteins of C. parvum calmodulin-like protein (CpCML). By constructing the cpcml bait plasmid, 5 potential CpCML - interacting proteins in C. parvum oocyst were screened by yeast-two-hybrid system (Y2H). Bimolecular fluorescence complementation (BiFC) and Co-immunoprecipitation (Co-IP) were performed as subsequent validations. Fibrillarin RNA methylase (FBL) was identified via this screening method as CpCML interacting protein in C. parvum. The identification of this interaction made it possible to get a further understanding of the function of CpCML and its contribution to the pathogenicity of C. parvum.
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http://dx.doi.org/10.1016/j.micpath.2022.105679DOI Listing
July 2022

The interaction mechanism of nickel ions with L929 cells based on integrative analysis of proteomics and metabolomics data.

Regen Biomater 2022 23;9:rbac040. Epub 2022 Jun 23.

State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, 2# Si Pailou, Nanjing 210096, China.

The aim of this article was to study the toxicity mechanism of nickel ions (Ni) on L929 cells by combining proteomics and metabolomics. First, iTRAQ-based proteomics and LC/MS metabolomics analyses were used to determine the protein and metabolite expression profiles in L929 cells after treatment with 100 μM Ni for 12, 24 and 48 h. A total of 177, 2191 and 2109 proteins and 40, 60 and 74 metabolites were found to be differentially expressed. Then, the metabolic pathways in which both differentially expressed proteins and metabolites were involved were identified, and three pathways with proteins and metabolites showing upstream and downstream relationships were affected at all three time points. Furthermore, the protein-metabolite-metabolic pathway network was constructed, and two important metabolic pathways involving 4 metabolites and 17 proteins were identified. Finally, the functions of the important screened metabolic pathways, metabolites and proteins were investigated and experimentally verified. Ni mainly affected the expression of upstream proteins in the glutathione metabolic pathway and the arginine and proline metabolic pathway, which further regulated the synthesis of downstream metabolites, reduced the antioxidant capacity of cells, increased the level of superoxide anions and the ratio of GSSG to GSH, led to oxidative stress, affected energy metabolism and induced apoptosis.
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http://dx.doi.org/10.1093/rb/rbac040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9258689PMC
June 2022

Fatigue Factor Assessment and Life Prediction of Concrete Based on Bayesian Regularized BP Neural Network.

Materials (Basel) 2022 Jun 25;15(13). Epub 2022 Jun 25.

Faculty of Urban Construction, Beijing University of Technology, Beijing 100124, China.

Concrete tensile properties usually govern the fatigue cracking of structural components such as bridge decks under repetitive loading. A fatigue life reliability analysis of commonly used ordinary cement concrete is desirable. As fatigue is affected by many interlinked factors whose effect is nonlinear, a unanimous consensus on the quantitative measurement of these factors has not yet been achieved. Benefiting from its unique self-learning ability and strong generalization capability, the Bayesian regularized backpropagation neural network (BR-BPNN) was proposed to predict concrete behavior in tensile fatigue. A total of 432 effective data points were collected from the literature, and an optimal model was determined with various combinations of network parameters. The average relative impact value (ARIV) was constructed to evaluate the correlation between fatigue life and its influencing parameters (maximum stress level Smax, stress ratio R, static strength , failure probability P). ARIV results were compared with other factor assessment methods (weight equation and multiple linear regression analyses). Using BR-BPNN, S-N curves were obtained for the combinations of R = 0.1, 0.2, 0.5; = 5, 6, 7 MPa; P = 5%, 50%, 95%. The tensile fatigue results under different testing conditions were finally compared for compatibility. It was concluded that Smax had the most significant negative effect on fatigue life; and the degree of influence of R, P, and , which positively correlated with fatigue life, decreased successively. ARIV was confirmed as a feasible way to analyze the importance of parameters and could be recommended for future applications. It was found that the predicted logarithmic fatigue life agreed well with the test results and conventional data fitting curves, indicating the reliability of the BR-BPNN model in predicting concrete tensile fatigue behavior. These probabilistic fatigue curves could provide insights into fatigue test program design and fatigue evaluation. Since the overall correlation coefficient between the prediction and experimental results reached 0.99, the experimental results of plain concrete under flexural tension, axial tension, and splitting tension could be combined in future analyses. Besides utilizing the valuable fatigue test data available in the literature, this work provided evidence of the successful application of BR-BPNN on concrete fatigue prediction. Although a more accurate and comprehensive method was derived in the current study, caution should still be exercised when utilizing this method.
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http://dx.doi.org/10.3390/ma15134491DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9267291PMC
June 2022
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