Publications by authors named "Wen Chen"

1,734 Publications

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CTLA-4 promotes lymphoma progression through tumor stem cell enrichment and immunosuppression.

Open Life Sci 2021 6;16(1):909-919. Epub 2021 Sep 6.

Department of Pathology, The 8th Medical Center, Chinese PLA General Hospital, Beijing 100091, China.

The recurrence rate of lymphoma is very high, and tumor stem cells may be an important mechanism. Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) can inhibit antitumor immunity and promote cancer progression, but its role and mechanism in lymphoma are still unclear. Here we collected lymphoma tissue and peripheral blood from patients with diffuse large B-cell lymphoma (DLBCL). Results showed that CTLA-4 expression and CD44+ cell in the high-risk group were significantly higher than that in the low-risk group. Correlation analysis showed that CTLA-4 expression positively correlated with CD44+ cell in lymphoma tissue and regulatory T (Treg) cells in lymphocytes. experiment showed that CTLA-4 increased the ratio of lymphoma stem cells, and proliferation and invasion of lymphoma cells through TGF-β pathway. Moreover, CTLA-4 enhanced the proliferation of Treg cells induced by lymphoma cells. Animal experiments showed that CTLA-4 can promote transplanted lymphoma growth. Immunohistochemistry results showed that both Ki-67 and CD44+ cells increased significantly in the CTLA-4 group. TGF-β neutralization can significantly block these effects of CTLA-4. In conclusion, CTLA-4 promoted DLBCL progression through lymphoma stem cell enrichment and immunosuppression.
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http://dx.doi.org/10.1515/biol-2021-0094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8422981PMC
September 2021

Neutral bots probe political bias on social media.

Nat Commun 2021 Sep 22;12(1):5580. Epub 2021 Sep 22.

Observatory on Social Media, Indiana University, Bloomington, IN, USA.

Social media platforms attempting to curb abuse and misinformation have been accused of political bias. We deploy neutral social bots who start following different news sources on Twitter, and track them to probe distinct biases emerging from platform mechanisms versus user interactions. We find no strong or consistent evidence of political bias in the news feed. Despite this, the news and information to which U.S. Twitter users are exposed depend strongly on the political leaning of their early connections. The interactions of conservative accounts are skewed toward the right, whereas liberal accounts are exposed to moderate content shifting their experience toward the political center. Partisan accounts, especially conservative ones, tend to receive more followers and follow more automated accounts. Conservative accounts also find themselves in denser communities and are exposed to more low-credibility content.
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http://dx.doi.org/10.1038/s41467-021-25738-6DOI Listing
September 2021

Tissue-based metabolomics reveals metabolic signatures and major metabolic pathways of gastric cancer with help of transcriptomic data from TCGA.

Biosci Rep 2021 Sep 22. Epub 2021 Sep 22.

Zhengzhou University, Zhengzhou, China.

Purpose:  The aim of this study was to screen differential metabolites of gastric cancer (GC) and identify the key metabolic pathways of GC.

Methods: GC (n=28) and matched paracancerous (PC) tissues were collected, and LC-MS/MS analysis were performed to detect metabolites of GC and PC tissues. Metabolite pathways based on differential metabolites were enriched by MetaboAnalyst, and genes related to metabolite pathways were identified using the KEGGREST function of the R software package. Transcriptomics data from The Cancer Genome Atlas (TCGA) was analyzed to obtain differentially expressed genes (DEGs) of GC. Overlapping genes were acquired from metabonimics and transcriptomics data. Pathway enrichment analysis was performed using String. The protein expression of genes was validated by the Human Protein Atlas (HPA) database.

Results: A total of 325 key metabolites were identified, 111 of which were differentially expressed between the GC and PC groups. Seven metabolite pathways enriched by MetaboAnalyst were chosen, and 361 genes were identified by KEGGREST. A total of 2831 DEGs were identified from the TCGA cohort. Of these, 1317 were down-regulated, and 1636 were up-regulated. Twenty-two overlapping genes were identified between genes related to metabolism and DEGs. Glycerophospholipid (GPL) metabolism is likely associated with GC, of which AGPAT9 and ETNPPL showed lower expressed in GC tissues.

Conclusions: We investigated the tissue-based metabolomics profile of GC, and several differential metabolites were identified. GPL metabolism may affect on progression of GC.
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http://dx.doi.org/10.1042/BSR20211476DOI Listing
September 2021

Eyebrow Reconstruction With Temporal Hairline Relay Flap.

J Craniofac Surg 2021 Sep 20. Epub 2021 Sep 20.

No. 14 Department, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Abstract: Eyebrow is one of the most important features of the face; the absence of eyebrows will cause a heavy psychological burden to patients. Existing brow reconstruction techniques are not perfect for every case of eyebrow defect. In this study, a patient who suffered from eyebrows loss after radiotherapy for hemangioma underwent eyebrow reconstruction with the relay transfer of a temporal hairline flap. The entire procedure was performed in the outpatient operating room. The temporal hairline flap was transferred to the eyebrow region in a relay and survived well without necrosis. In the 2-month follow-up, the shape and density of the reconstructed eyebrows were satisfactory. The operation showed this technique was innovative, economic, and recommended as a suitable choice for eyebrow reconstruction, especially in those patients with poor hair transplantation recipient area.
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http://dx.doi.org/10.1097/SCS.0000000000008202DOI Listing
September 2021

Clinical Study of Stellate Ganglion Block Combined with General Anesthesia on Hemodynamics, Cognitive Function, and Gastrointestinal Function in Elderly Patients Undergoing Partial Hepatectomy.

Evid Based Complement Alternat Med 2021 7;2021:1426753. Epub 2021 Sep 7.

Department of Anesthesiology, Yuebei People's Hospital Affiliated to Shantou University Medical College, Shaoguan, Guangdong 512026, China.

Partial hepatectomy under general anesthesia is prone to hemodynamic alterations, and stress reactions are the main contributing factors to postoperative cognitive function in elderly partial hepatectomy patients. Postoperative cognitive dysfunction increases the incidence of postoperative complications and long-term morbidity and mortality in elderly patients. With the increasing trend of aging population and the gradual increase of elderly people undergoing surgical treatment, it is especially important to study the corresponding prevention and treatment measures. In this study, a total of 90 patients with primary liver cancer who received hepatectomy in our hospital from July 2020 to July 2021 were included as the research subject. The changes in hemorheology, stress-related indexes, cognitive function, postoperative pain, and gastrointestinal function were compared between the two groups The results showed that SGB combined with general anesthesia can effectively reduce hemodynamic fluctuations in elderly partial hepatectomy patients, alleviate surgical stress, promote postoperative recovery of cognitive function and gastrointestinal function with high safety, and is worthy of clinical promotion.
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http://dx.doi.org/10.1155/2021/1426753DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8443347PMC
September 2021

Naturally acquired HPV antibodies against subsequent homotypic infection: A large-scale prospective cohort study.

Lancet Reg Health West Pac 2021 Aug 16;13:100196. Epub 2021 Jul 16.

State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Strait Collaborative Innovation Center of Biomedicine and Pharmaceutics, School of Public Health, Xiamen University, Xiamen, Fujian, China.

Background: Although recent studies have suggested that naturally acquired Human papillomavirus (HPV) antibodies are partly protective against subsequent homotypic infection, the extent of protection remains indecisive. Here, we evaluate the protective effect of neutralizing and IgG antibodies simultaneously.

Methods: In a cohort of 3634 women aged 18-45 years from the control arm of a phase III trial of the HPV-16/18 bivalent vaccine, participants were tested for neutralizing antibodies by pseudovirion-based neutralization assay (PBNA) and IgG antibodies by enzyme-linked immunosorbent assay (ELISA) at baseline. HPV-16/18 incident and persistent infections were identified using cervical specimens periodically collected during the 5·5 years of follow-up. The protective effects of HPV-16/18 neutralizing and IgG antibodies against homotypic infection were assessed using a Cox proportional hazard model.

Findings: For the persistent infection (PI) endpoints of HPV-16/18 lasting for over 6/12 months, a prevalence of type-specific neutralizing antibodies was highly protective (6-month PI: hazard ratio (HR) = 0·16, 95% confidence interval (CI): 0·04, 0·65; 12-month PI: HR = 0·23, 95% CI: 0·06, 0·94), whereas a prevalence of IgG antibodies was associated with minor and non-significant protection (6-month PI: HR = 0·66, 95% CI: 0·40, 1·09; 12-month PI: HR = 0·66, 95% CI: 0·36, 1·20). After increasing the cut-off value to the median IgG level, the risk of 6-month PI was significantly lower in seropositive vs seronegative women (HR = 0·38, 95% CI: 0·18, 0·83).

Interpretation: Naturally acquired antibodies are associated with a substantially reduced risk of subsequent homotypic infection.

Funding: NSFC; The Fujian Province Health Education Joint Research Project; Xiamen Science and Technology Major Project; CIFMS; and Xiamen Innovax.
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http://dx.doi.org/10.1016/j.lanwpc.2021.100196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8403914PMC
August 2021

Use of Buried Guide Needle to Fix Inferior Eyelid Orbital Septum Fat for Tear Trough Depression Filling.

J Craniofac Surg 2021 Sep 14. Epub 2021 Sep 14.

No. 14 Department, Plastic Surgery Hospital, Chinese Academy of Medical Sciences, Beijing China.

Abstract: Fat fixation is a key step in filling tear trough depression with inferior eyelid orbital septum fat. The ideal position for inferior eyelid fat fixation is to cross the tear trough ligament causing tear trough depression and the orbicularis retaining ligament, with the distal end fixed at the farthest end of the dissected lacuna deep down the inferior orbicularis oculi muscle. Traditional suturing is difficult in the deep narrow lacunae, but a buried guide needle can be used to suture and fix the fat in the deepest lacuna. In this study, 264 patients who underwent tear trough filling using a buried guide needle to fix the released inferior eyelid orbital septum fat from 2017 to 2020 were followed up. The preoperative and postoperative imaging findings were compared to evaluate the effectiveness of the operation and postoperative complications. The inferior eyelid bulging, loose skin, and tear trough depression significantly improved than that before the operation. None of the patients had any severe complications, such as inferior eyelid ectropion, lagophthalmos, scar hyperplasia, and diplopia, in the long term (6 months) postoperatively. Five patients showed mild eyelid-eyeball separation and recovered in 1 month. Four patients had diplopia, and 3 patients had chemosis; all recovered in 7 days. The tear trough depression was not corrected completely in 2 patients. The operation showed satisfactory results in the improvement of tear trough depression in addition to alleviation of inferior eyelid bulging and loose inferior eyelid skin that is caused by the traditional inferior eyelid pouch removal.
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http://dx.doi.org/10.1097/SCS.0000000000008131DOI Listing
September 2021

Malware detection based on semi-supervised learning with malware visualization.

Math Biosci Eng 2021 07;18(5):5995-6011

School of Cyber Science and Engineering, Sichuan University, China.

The traditional signature-based detection method requires detailed manual analysis to extract the signatures of malicious samples, and requires a large number of manual markers to maintain the signature library, which brings a great time and resource costs, and makes it difficult to adapt to the rapid generation and mutation of malware. Methods based on traditional machine learning often require a lot of time and resources in sample labeling, which results in a sufficient inventory of unlabeled samples but not directly usable. In view of these issues, this paper proposes an effective malware classification framework based on malware visualization and semi-supervised learning. This framework includes mainly three parts: malware visualization, feature extraction, and classification algorithm. Firstly, binary files are processed directly through visual methods, without assembly, decompression, and decryption; Then the global and local features of the gray image are extracted, and the visual image features extracted are fused on the whole by a special feature fusion method to eliminate the exclusion between different feature variables. Finally, an improved collaborative learning algorithm is proposed to continuously train and optimize the classifier by introducing features of inexpensive unlabeled samples. The proposed framework was evaluated over two extensively researched benchmark datasets, i.e., Malimg and Microsoft. The results show that compared with traditional machine learning algorithms, the improved collaborative learning algorithm can not only reduce the cost of sample labeling but also can continuously improve the model performance through the input of unlabeled samples, thereby achieving higher classification accuracy.
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http://dx.doi.org/10.3934/mbe.2021300DOI Listing
July 2021

Malware detection based on semi-supervised learning with malware visualization.

Math Biosci Eng 2021 07;18(5):5995-6011

School of Cyber Science and Engineering, Sichuan University, China.

The traditional signature-based detection method requires detailed manual analysis to extract the signatures of malicious samples, and requires a large number of manual markers to maintain the signature library, which brings a great time and resource costs, and makes it difficult to adapt to the rapid generation and mutation of malware. Methods based on traditional machine learning often require a lot of time and resources in sample labeling, which results in a sufficient inventory of unlabeled samples but not directly usable. In view of these issues, this paper proposes an effective malware classification framework based on malware visualization and semi-supervised learning. This framework includes mainly three parts: malware visualization, feature extraction, and classification algorithm. Firstly, binary files are processed directly through visual methods, without assembly, decompression, and decryption; Then the global and local features of the gray image are extracted, and the visual image features extracted are fused on the whole by a special feature fusion method to eliminate the exclusion between different feature variables. Finally, an improved collaborative learning algorithm is proposed to continuously train and optimize the classifier by introducing features of inexpensive unlabeled samples. The proposed framework was evaluated over two extensively researched benchmark datasets, i.e., Malimg and Microsoft. The results show that compared with traditional machine learning algorithms, the improved collaborative learning algorithm can not only reduce the cost of sample labeling but also can continuously improve the model performance through the input of unlabeled samples, thereby achieving higher classification accuracy.
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http://dx.doi.org/10.3934/mbe.2021300DOI Listing
July 2021

A Simple and Efficient Solution to Eliminate Evaporation in Mammalian Embryo Cultures.

Cell Reprogram 2021 Sep 3. Epub 2021 Sep 3.

VitaVitro Biotech Co., Ltd., Shenzhen, China.

The aim of this brief report is to offer a solution for a problem that compromises the quality of -produced mammalian embryos. The harmful effects of evaporation-induced osmotic changes in mammalian embryo cultures have been recognized only recently. In this technical report, we describe a modified embryo culture dish (Humdish) that provides consistent >97% humidity and fully eliminates osmotic changes in the commonly used drop-under-oil culture systems from day 0 to 6. As an additional benefit, the Humdish also increases the temperature stability of cultures. If subsequent laboratory and clinical experiments prove its value, our suggested approach may help to improve the environment and quality of all preimplantation stage mammalian embryos, including the most sensitive ones produced from artificial gametes or by somatic cell nuclear transfer.
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http://dx.doi.org/10.1089/cell.2021.0061DOI Listing
September 2021

Redistribution of mineral phases of incineration bottom ash by size and magnetic separation and its effects on the leaching behaviors.

Environ Pollut 2021 Aug 24;290:118015. Epub 2021 Aug 24.

The Residues and Resource Reclamation Centre, Nanyang Environment and Water Research Institute, Nanyang Technological University, 1 Cleantech Loop, CleanTech One, 637141, Singapore; School of Civil and Environmental Engineering, Nanyang Technological University, 50 Nanyang Avenue, 639798, Singapore. Electronic address:

Size and magnetic separation of incineration bottom ash (IBA) are common for ferrous metals recovery, however, their influences on the mineral phase and the element redistribution, and subsequently the induced variation of metal leaching potential herein remain limited understanding. The lack of research in this field may misunderstand IBA performances, cause confused results for comparison among various studies, and potentially lead to biased conclusions. We herein quantitatively investigate the effects of size and magnetic separation on the IBA based on element distribution, leaching behavior, morphology, and mineralogy with statistical analysis. For preparation, sieving was performed with the original IBA (to obtain 7 size-fractions termed as OR1-7, respectively), followed by magnetic separation of each, to further yield magnetic fractions (MF1-7) to discriminate nonmagnetic fractions (NF1-7). In this study, we show that size and magnetic separation may pose significant yet different impacts on different fractions, which would affect their leaching potential concerning their respective downstream applications.
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http://dx.doi.org/10.1016/j.envpol.2021.118015DOI Listing
August 2021

Pradefovir Treatment in Patients with Chronic Hepatitis B: Week 24 Results from a Multicenter, Double-blind, Randomized, Noninferiority, Phase 2 Trial.

Clin Infect Dis 2021 Sep 6. Epub 2021 Sep 6.

Department of Quality management, The 5th medical center of Chinese PLA General Hospital, Beijing, China.

Objectives: Pradefovir is a liver-targeted prodrug of adefovir, a nucleotide analog with antiviral activity against hepatitis B virus (HBV) DNA polymerase. This phase 2 study compared the efficacy and safety of oral pradefovir (30mg, 45mg, 60mg, and 75mg) versus tenofovir disoproxil fumarate (TDF; 300mg) and aimed to identify the most appropriate dose of pradefovir for the forthcoming phase 3 study.

Methods: Treatment-naive and experienced (not on treatment >6 months) patients with chronic hepatitis B were eligible.

Results: A total of 240 participants were randomized and treated in the study (48 per group). Approximately 80% were HBeAg positive and 10% had liver cirrhosis. The reductions from baseline in HBV DNA levels achieved at week 24 were 5.40, 5.34, 5.33, and 5.40 log10 IU/ml with pradefovir doses of 30mg, 45mg, 60mg, and 75mg, respectively, compared to 5.12 log10 IU/ml with TDF. However, HBeAg loss was attained by more participants who received 45mg, 60mg or 75mg pradefovir than those receiving TDF (12%, 6%, 9% vs. 3%). The TDF group exhibited a more significant increase in serum creatinine than the pradefovir 30mg or 45mg groups, and serum phosphate levels were comparable among all groups. Most adverse events were mild (grade 1). No treatment-related severe adverse events were reported. Overall, adverse events and laboratory abnormalities were comparable to the TDF group.

Conclusions: Pradefovir exhibited comparable reductions in HBV DNA levels to TDF. All treatments were safe and well tolerated.
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http://dx.doi.org/10.1093/cid/ciab763DOI Listing
September 2021

The Pathogenesis of Eosinophilic Asthma: A Positive Feedback Mechanism That Promotes Th2 Immune Response Filaggrin Deficiency.

Front Immunol 2021 13;12:672312. Epub 2021 Aug 13.

Pulmonary and Critical Care Medicine College of Chinese PLA General Hospital, 8th Medical Center of Chinese PLA General Hospital, Beijing, China.

Eosinophilic asthma (EA) is a common subtype of asthma and often progresses to severe disease. In order to understand its pathogenesis, targeted next-generation gene sequencing was performed on 77 Chinese EA patients and 431 Chinese healthy controls to obtain differential genomic variations. Among the 41 Single Nucleotide Polymorphisms (SNPs) screened for mutation sites in more than 3 patients, filaggrin gene rs192116923 T>G and rs75235053 C>G were newly found to be associated with EA patients with atopic dermatitis (AD) (P <0.001) and severe EA (P=0.032), respectively. Filaggrin has been shown to be mainly expressed in epithelial cells and plays an important role in formation of an effective skin barrier. Bioinformatic analysis indicated rs192116923 T>G may increase the binding of Smad3 to transmit TGF-β1 signaling, and thereby inhibit filaggrin expression, and rs75235053 C>G may add new splicing sites to reduce filaggrin monomers. It has been known that the level of Th2 cytokine IL-4 is increased in EA patients, and IL-4 increases airway epithelial permeability and enhances inflammatory response through some unclear mechanisms. To figure out whether filaggrin is involved in immune responses in asthma, we have treated human respiratory epithelial cell line BEAS-2B cells with IL-4 and found that the expression levels of filaggrin and E-cadherin decreased significantly in a time and dose-dependent manner, suggesting that IL-4 increased airway epithelial permeability by reducing filaggrin and adhesion molecule. In addition, in our study, IL-4 increased the expression of epithel-derived inflammatory cytokines IL-33 and TSLP which further enhanced the Th2 inflammatory response. To investigate the role of filaggrin in development of EA, knockdown filaggrin with siRNA revealed a decrease in E-cadherin levels, which were further down-regulated by IL-4 stimulation. Knockdown of filaggrin alone did not affect the levels of IL-33 and TSLP, but further exacerbated the decrease of IL-33/TSLP caused by IL-4, suggesting that filaggrin may involve in IL-4R signaling pathway to regulate the level of IL-33/TSLP. In conclusion, in the Th2 cytokine milieu of asthma, deficient mutation in airway epithelial cells may increase the epithelial permeability and the expression of IL-33/TSLP which positively feedback the Th2 inflammation response.
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http://dx.doi.org/10.3389/fimmu.2021.672312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8414997PMC
August 2021

miR-195-5p regulates cell proliferation, apoptosis, and invasion of thyroid cancer by targeting telomerase reverse transcriptase.

Bioengineered 2021 12;12(1):6201-6209

Department Of Head And Neck Surgery, Jiangxi Provincial Cancer Hospital, Jiangxi Cancer Hospital of Nanchang University, Jiangxi Provincial Key Laboratory of Translational Medicine and Oncology, Jiangxi Cancer Center, Nanchang, Jiangxi, China.

In most human primary cancers, the expression, or telomerase activity, of telomerase reverse transcriptase () is detectable. However, the mechanism ofactivity within oncogenesis of thyroid cancer remains largely unknown. In this study, we identified miR-195-5p as having involvement in cell proliferation, apoptosis, and invasion in human thyroid cancer. MTT was used to measure cell proliferation, Transwell chamber was used to measure invasion. Western blotting was used to detect the expressions of TERT, PCNA, and Ki67. Target gene prediction software predicted that TERT may be the target gene of miR-195-5p. Luciferase reporting system was used to identify the targeting relationship. A significant increase of in TERT expression was observed by immunohistochemistry compared with normal tissue, however, a decrease in miR-195-5p expression using qRT-PCRand western blot compared with normal cells. Functional analysis demonstrates that miR-195-5p negatively correlated withand inhibitedexpression through its interaction with the3'-untranslatedregion (3'-UTR). Overexpression of miR-195-5p was shown to inhibit proliferation and invasion, and promote apoptosis of CAL-62 thyroid cancer cells. miR-195-5p-mediatedeffects were rescued by the overexpression of. Altogether, our data demonstrate that miR-195-5p regulates cell proliferation, apoptosis, and invasion in human thyroid cancer via, providing evidence of a new potential therapeutic target for further investigation.
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http://dx.doi.org/10.1080/21655979.2021.1963908DOI Listing
December 2021

Association between Alzheimer's disease and risk of cancer: A retrospective cohort study in Shanghai, China.

Alzheimers Dement 2021 Sep 5. Epub 2021 Sep 5.

Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Introduction: We investigated the association between Alzheimer's disease (AD) and the risk of cancer in the Chinese population.

Methods: In this retrospective cohort study, multivariate Cox proportional hazard regression analysis was used to determine the correlation between AD and the risk of various cancers, as shown by hazard ratios (HRs) with 95% confidence intervals (CIs).

Results: Of 8097 AD patients, the HR for all subsequent cancers was 0.822 (95% CI, 0.728-0.928; P = .002). Among them, three specific cancers were associated with AD: lung cancer (HR, 0.656; 95% CI, 0.494- 0.871; P = .004), prostate and testicular cancer (HR, 0.414; 95% CI, 0.202-0.847; P = .016), and lymphoma (HR, 2.202; 95% CI, 1.005-4.826; P = .049).

Conclusion: Patients with AD might have a lower chance of developing several cancers, including lung cancer and prostate and testicular cancer. Meanwhile, a positive association between AD and a higher incident rate of lymphoma was observed.
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http://dx.doi.org/10.1002/alz.12436DOI Listing
September 2021

Correction to: CAFT: a deep learning-based comprehensive abdominal fat analysis tool for large cohort studies.

MAGMA 2021 Sep 4. Epub 2021 Sep 4.

Department of Diagnostic Radiology, Tan Tock Seng Hospital, 11 Jln Tan Tock Seng, Singapore, 308433, Singapore.

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http://dx.doi.org/10.1007/s10334-021-00956-7DOI Listing
September 2021

Development of models for cervical cancer screening: construction in a cross-sectional population and validation in two screening cohorts in China.

BMC Med 2021 09 3;19(1):197. Epub 2021 Sep 3.

Department of Cancer Epidemiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 South Panjiayuan Lane, Beijing, China.

Background: Current methods for cervical cancer screening result in an increased number of referrals and unnecessary diagnostic procedures. This study aimed to develop and evaluate a more accurate model for cervical cancer screening.

Methods: Multiple predictors including age, cytology, high-risk human papillomavirus (hrHPV) DNA/mRNA, E6 oncoprotein, HPV genotyping, and p16/Ki-67 were used for model construction in a cross-sectional population including women with normal cervix (N = 1085), cervical intraepithelial neoplasia (CIN, N = 279), and cervical cancer (N = 551) to predict CIN2+ or CIN3+. A base model using age, cytology, and hrHPV was calculated, and extended versions with additional biomarkers were considered. External validations in two screening cohorts with 3-year follow-up were further conducted (N = 3179, N = 3082).

Results: The base model increased the area under the curve (AUC, 0.91, 95% confidence interval [CI] = 0.88-0.93) and reduced colposcopy referral rates (42.76%, 95% CI = 38.67-46.92) compared to hrHPV and cytology co-testing in the cross-sectional population (AUC 0.80, 95% CI = 0.79-0.82, referrals rates 61.62, 95% CI = 59.4-63.8) to predict CIN2+. The AUC further improved when HPV genotyping and/or E6 oncoprotein were included in the base model. External validation in two screening cohorts further demonstrated that our models had better clinical performances than routine screening methods, yielded AUCs of 0.92 (95% CI = 0.91-0.93) and 0.94 (95% CI = 0.91-0.97) to predict CIN2+ and referrals rates of 17.55% (95% CI = 16.24-18.92) and 7.40% (95% CI = 6.50-8.38) in screening cohort I and II, respectively. Similar results were observed for CIN3+ prediction.

Conclusions: Compared to routine screening methods, our model using current cervical screening indicators can improve the clinical performance and reduce referral rates.
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http://dx.doi.org/10.1186/s12916-021-02078-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8414700PMC
September 2021

Oxidation of Primary Alcohols and Aldehydes to Carboxylic Acids via Hydrogen Atom Transfer.

Org Lett 2021 Sep 16;23(17):6648-6653. Epub 2021 Aug 16.

Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, Yunnan Provincial Center for Research and Development of Natural Products, School of Chemical Science and Technology, Yunnan University, Kunming, Yunnan 650091, People's Republic of China.

The oxidation of primary alcohols and aldehydes to the corresponding carboxylic acids is a fundamental reaction in organic synthesis. In this paper, we report a new chemoselective process for the oxidation of primary alcohols and aldehydes. This metal-free reaction features a new oxidant, an easy to handle procedure, high isolated yields, and good to excellent functional group tolerance even in the presence of vulnerable secondary alcohols and -butanesulfinamides.
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http://dx.doi.org/10.1021/acs.orglett.1c02188DOI Listing
September 2021

Programmable dual responsive system reconstructing nerve interaction with small-diameter tissue-engineered vascular grafts and inhibiting intimal hyperplasia in diabetes.

Bioact Mater 2022 Jan 25;7:466-477. Epub 2021 Jun 25.

Department of Cell Biology, Third Military Army Medical University, Chongqing, 400038, China.

Small-diameter tissue-engineered vascular grafts (sdTEVGs) with hyperglycemia resistance have not been constructed. The intimal hyperplasia caused by hyperglycemia remains problem to hinder the patency of sdTEVGs. Here, inspired by bionic regulation of nerve on vascular, we found the released neural exosomes could inhibit the abnormal phenotype transformation of vascular smooth muscle cells (VSMCs). The transformation was a prime culprit causing the intimal hyperplasia of sdTEVGs. To address this concern, sdTEVGs were modified with an on-demand programmable dual-responsive system of ultrathin hydrogels. An external primary Reactive Oxygen Species (ROS)-responsive Netrin-1 system was initially triggered by local inflammation to induce nerve remolding of the sdTEVGs overcoming the difficulty of nerve regeneration under hyperglycemia. Then, the internal secondary ATP-responsive DENND1A (guanine nucleotide exchange factor) system was turned on by the neurotransmitter ATP from the immigrated nerve fibers to stimulate effective release of neural exosomes. The results showed nerve fibers grow into the sdTEVGs in diabetic rats 30 days after transplantation. At day 90, the abnormal VSMCs phenotype was not detected in the sdTEVGs, which maintained long-time patency without intima hyperplasia. Our study provides new insights to construct vascular grafts resisting hyperglycemia damage.
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http://dx.doi.org/10.1016/j.bioactmat.2021.05.034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8379357PMC
January 2022

Pembrolizumab associated Stevens-Johnson syndrome with porokeratosis in a patient in the setting of primary hepatocellular carcinoma.

Australas J Dermatol 2021 Aug 31. Epub 2021 Aug 31.

Department of Dermatology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.

Pembrolizumab is a humanised therapeutic antibody against the PD-1 receptor. It has been used in various advanced cancer immunotherapies. Here, we report an extremely rare case of a 32-year-old man who developed Stevens-Johnson syndrome (SJS) with porokeratosis simultaneously during pembrolizumab treatment for primary hepatocellular carcinoma (T3N1M1).
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http://dx.doi.org/10.1111/ajd.13704DOI Listing
August 2021

IKKε knockout alleviates angiotensin II-induced apoptosis and excessive autophagy in vascular smooth muscle cells by regulating the ERK1/2 pathway.

Exp Ther Med 2021 Oct 23;22(4):1051. Epub 2021 Jul 23.

Department of Thoracic and Cardiovascular Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, P.R. China.

Inhibitor of nuclear factor-κB kinase subunit ε (IKKε) is an important signal regulator in the formation of abdominal aortic aneurysm (AAA). However, the underlying mechanism remains to be elucidated. Therefore, the present study aimed to investigate the mechanism underlying IKKε function in AAA formation by studying apoptosis and autophagy in angiotensin II (Ang II)-induced vascular smooth muscle cells (VSMCs). AngII was used to stimulate VSMCs for 24 h to simulate the process of AAA formation. VSMCs were transfected with IKKε small interfering RNA to investigate the effect of IKKε on AAA formation, cell apoptosis and autophagy. IKKε deficiency led to reduced mitochondrial damage and apoptosis in VSMCs in the early stage of apoptosis , as demonstrated using a JC-1 probe. IKKε deficiency also reduced autophagy and decreased the formation of autophagic vacuoles in VSMCs, demonstrated using transmission electron microscopy. The decrease in apoptosis caused by IKKε knockdown was reversed when the autophagic flow was blocked using bafilomycin A1. Western blot analysis further revealed that IKKε deficiency negatively regulated the ERK1/2 signaling pathway to reduce autophagy. Collectively, the results of the present study revealed that IKKε played a key role in apoptosis by inducing excessive autophagy, thereby potentially contributing to AAA formation. These findings further revealed the mechanism underlying IKKε function in the formation of AAA.
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http://dx.doi.org/10.3892/etm.2021.10485DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8353624PMC
October 2021

Extended mining of the oil biosynthesis pathway in biofuel plant Jatropha curcas by combined analysis of transcriptome and gene interactome data.

BMC Bioinformatics 2021 Aug 18;22(Suppl 6):409. Epub 2021 Aug 18.

CAS Key Laboratory of Tropical Plant Resources and Sustainable Use, Xishuangbanna Tropical Botanical Garden, Chinese Academy of Sciences, Kunming, 650223, Yunnan, China.

Background: Jatropha curcas L. is an important non-edible oilseed crop with a promising future in biodiesel production. However, little is known about the molecular biology of oil biosynthesis in this plant when compared with other established oilseed crops, resulting in the absence of agronomically improved varieties of Jatropha. To extensively discover the potentially novel genes and pathways associated with the oil biosynthesis in J. curcas, new strategy other than homology alignment is on the demand.

Results: In this study, we proposed a multi-step computational framework that integrates transcriptome and gene interactome data to predict functional pathways in non-model organisms in an extended process, and applied it to study oil biosynthesis pathway in J. curcas. Using homologous mapping against Arabidopsis and transcriptome profile analysis, we first constructed protein-protein interaction (PPI) and co-expression networks in J. curcas. Then, using the homologs of Arabidopsis oil-biosynthesis-related genes as seeds, we respectively applied two algorithm models, random walk with restart (RWR) in PPI network and negative binomial distribution (NBD) in co-expression network, to further extend oil-biosynthesis-related pathways and genes in J. curcas. At last, using k-nearest neighbors (KNN) algorithm, the predicted genes were further classified into different sub-pathways according to their possible functional roles.

Conclusions: Our method exhibited a highly efficient way of mining the extended oil biosynthesis pathway of J. curcas. Overall, 27 novel oil-biosynthesis-related gene candidates were predicted and further assigned to 5 sub-pathways. These findings can help better understanding of the oil biosynthesis pathway of J. curcas, as well as paving the way for the following J. curcas breeding application.
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http://dx.doi.org/10.1186/s12859-021-04319-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8375076PMC
August 2021

Synthesis of Highly Functionalized Pyridines: A Metal-Free Cascade Process.

Org Lett 2021 Sep 18;23(17):6669-6673. Epub 2021 Aug 18.

Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, Yunnan Provincial Center for Research and Development of Natural Products, School of Chemical Science and Technology, Yunnan University, Kunming, Yunnan 650091, P. R. China.

Herein, we report a new process for the synthesis of highly functionalized pyridines based on a tandem Pummerer-type rearrangement, aza-Prins cyclization, and elimination-induced aromatization. This formal [5+1] cyclization provides pyridines in good yields with easily accessible starting materials. The synthetic potential of our new method is further demonstrated in the modification of the frameworks of BINOL and some natural products.
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http://dx.doi.org/10.1021/acs.orglett.1c02234DOI Listing
September 2021

Laparoscopic pectopexy: the learning curve and comparison with laparoscopic sacrocolpopexy.

Int Urogynecol J 2021 Aug 18. Epub 2021 Aug 18.

Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, No. 123, Dapi Road, Niaosong District, Kaohsiung City, 833401, Taiwan.

Introduction And Hypothesis: In addition to laparoscopic sacrocolpopexy (LS), laparoscopic pectopexy (LP) is a novel surgical method for correcting apical prolapse. The descended cervix or vaginal vault is suspended with a synthetic mesh by fixing the bilateral mesh ends to the pectineal ligaments. This study was aimed at developing a learning curve for LP and to compare it with results with LS.

Methods: We started laparoscopic/robotic pectopexy in our department in August 2019. This retrospective study included the initial 18 consecutive women with apical prolapse receiving LP and another group undergoing LS (21 cases) performed by the same surgeon. The medical and video records were reviewed.

Results: The age was older in the LP group than in the LS group (65.2 vs 53.1 years). The operation time of LP group was significantly shorter than that of the LS group (182.9 ± 27.2 vs 256.2 ± 45.5 min, p < 0.001). The turning point of the LP learning curve was observed at the 12th case. No major complications such as bladder, ureteral, bowel injury or uncontrolled bleeding occurred in either group. Postoperative low back pain and defecation symptoms occurred exclusively in the LS group. During the follow-up period (mean 7.2 months in LP, 16.2 months in LS), none of the cases had recurrent apical prolapse.

Conclusions: Laparoscopic pectopexy is a feasible surgical method for apical prolapse, with a shorter operation time and less postoperative discomfort than LS. LP may overcome the steep learning curve of LS because the surgical field of LP is limited to the anterior pelvis and avoids encountering the critical organs.
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http://dx.doi.org/10.1007/s00192-021-04934-4DOI Listing
August 2021

Magnetic Stiffening in 3D Cell Culture Matrices.

Nano Lett 2021 08 13;21(16):6740-6747. Epub 2021 Aug 13.

Radboud University, Institute for Molecules and Materials, Heyendaalseweg 135, 6525 AJ Nijmegen, The Netherlands.

The mechanical environment of a cell is not constant. This dynamic behavior is exceedingly difficult to capture in (synthetic) matrices. This paper describes a novel, highly adaptive hybrid hydrogel composed of magnetically sensitive magnetite nanorods and a stress-responsive synthetic matrix. Nanorod rearrangement after application of (small) magnetic fields induces strain in the network, which results in a strong (over 10-fold) stiffening even at minimal (2.5 wt %) nanorod concentrations. Moreover, the stiffening mechanism yields a fast and fully reversible response. In the manuscript, we quantitatively analyze that forces generated by the particles are comparable to cellular forces. We demonstrate the value of magnetic stiffening in a 3D MCF10A epithelial cell experiment, where simply culturing on top of a permanent magnet gives rise to changes in the cell morphology. This work shows that our hydrogels are uniquely suited as 3D cell culture systems with on-demand adaptive mechanical properties.
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http://dx.doi.org/10.1021/acs.nanolett.1c00371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8392345PMC
August 2021

Towards improved detection and identification of rust fungal pathogens in environmental samples using a metabarcoding approach.

Phytopathology 2021 Aug 12. Epub 2021 Aug 12.

Agriculture and Agri-Food Canada Central Experimental Farm, 98674, Science & Technology Branch, Ottawa, Ontario, Canada;

The dispersion of fungal inocula such as the airborne spores of rust fungi (Pucciniales) can be monitored by metabarcoding the internal transcribed spacer 2 (ITS2) of the rRNA gene in environmental DNAs. This is largely dependent upon a high-quality reference database (refDB) and primers with proper taxonomic coverage and specificity. For this study, a curated ITS2 reference database (named CR-ITS2-refDB) comprising representatives of the major cereal rust fungi and phylogenetically related species was compiled. Inter- and intra-specific variation analyses suggested that the ITS2 region had reasonable discriminating power for the majority of the species or species complexes in the database. evaluation of nine forward and seven reverse ITS2 primers, including three newly designed, revealed marked variation in DNA amplification efficiency for the rusts. The theoretical assessment of rust-enhanced (Rust2inv/ITS4var_H) and universal fungal (ITS9F/ITS4) ITS2 primer pairs was validated by profiling the airborne rust fungal communities from environmental samples using a metabarcoding approach. Species or subspecific level identification of the rusts was improved by using CR-ITS2-refDB, and the Automated Oligonucleotide Design Pipeline (AODP), which identified all mutations distinguishing highly conserved DNA markers amongst close relatives. A generic bioinformatics pipeline was developed, including all steps employed in this study from evaluation of primers to accurate identification of short metabarcodes at the level of interest for defining phytopathogens. The results highlighted the importance of primer selection, refDBs that are resolved to reflect phylogenetic relationships, and the use of AODP for improving the reliability of metabarcoding in phytopathogen biosurveillance.
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http://dx.doi.org/10.1094/PHYTO-01-21-0020-RDOI Listing
August 2021

Spatiotemporal distribution and sociodemographic and socioeconomic factors associated with primary and secondary syphilis in Guangdong, China, 2005-2017.

PLoS Negl Trop Dis 2021 Aug 12;15(8):e0009621. Epub 2021 Aug 12.

School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong, China.

Background: Previous studies exploring the factors associated with the incidence of syphilis have mostly focused on individual-level factors. However, recent evidence has indicated that social-level factors, such as sociodemographic and socioeconomic factors, also affect the incidence of syphilis. Studies on the sociodemographic and socioeconomic factors associated with syphilis incidence are scarce, and they have rarely controlled for spatial effects, even though syphilis shows spatial autocorrelation.

Methodology/principal Findings: Syphilis data from 21 cities in Guangdong province between 2005 and 2017 were provided by the National Notifiable Infectious Disease Reporting Information System. The incidence time series, incidence map, and space-time scanning data were used to visualize the spatiotemporal distribution. The spatial panel data model was then applied to explore the relationship between sociodemographic factors (population density, net migration rate, male:female ratio, and the number of health institutions per 1,000 residents), socioeconomic factors (gross domestic product per capita, the proportion of secondary/tertiary industry), and the incidence of primary and secondary syphilis after controlling for spatial effects. The incidence of syphilis increased slowly from 2005 (11.91 per 100,000) to 2011 (13.42 per 100,000) and then began to decrease, reaching 6.55 per 100,000 in 2017. High-risk clusters of syphilis tended to shift from developed areas to underdeveloped areas. An inverted U-shaped relationship was found between syphilis incidence and gross domestic product per capita. Moreover, syphilis incidence was significantly associated with population density (β = 2.844, P = 0.006), the number of health institutions per 1,000 residents (β = -0.095, P = 0.007), and the net migration rate (β = -0.219, P = 0.002).

Conclusions/significance: Our findings suggest that the incidence of primary and secondary syphilis first increase before decreasing as economic development increases further. These results emphasize the necessity to prevent syphilis in regions at the early stages of economic growth.
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http://dx.doi.org/10.1371/journal.pntd.0009621DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8407558PMC
August 2021

The in-plane metal contacted 5.1 nm Janus WSSe Schottky barrier field-effect transistors.

Nanotechnology 2021 Aug 11. Epub 2021 Aug 11.

Guangdong Guangxin Ion Beam Technology Co., Ltd, Guangzhou, Guangzhou, 510000, CHINA.

Edge contact between two-dimensional materials and metal can achieve small contact resistance because of strong interaction. In this work, we investigated the electronic transport of in-plane (IP) heterojunctions based on Ti/WSSe and Sn/WSSe using first principle calculations. The results showed that the interface bonding and metallization are found on the IP Ti/WSSe and Sn/WSSe contact interface, indicating that the Ohmic contacts are formed between Ti, Sn and WSSe. Then, we constructed double-gate model to investigate the performance of the IP Ti and Sn contacted 5.1 nm WSSe Schottky barrier field-effect transistors (SBFETs). The calculated on-state current of the IP Ti contacted 5.1 nm WSSe SBFETs is 406.3 μA/μm. While, the on-state current of the Sn contacted 5.1 nm WSSe SBFETs reachs up to 1104.2 μA/μm, which is far beyond the requirements of the requirements of International Technology Roadmap for Semiconductor (ITRS) HP application targets. Our study will provide a guide for high performance transistors based on IP metal/WSSe configurations in the future.
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http://dx.doi.org/10.1088/1361-6528/ac1cc2DOI Listing
August 2021

An activatable near-infrared fluorescent probe facilitated high-contrast lipophagic imaging in live cells.

Chem Commun (Camb) 2021 Sep 10;57(69):8664-8667. Epub 2021 Aug 10.

State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, P. R. China.

A new fluorescent probe (Q-lipo) was developed by conjugating a xanthene scaffold with a quinoline moiety for activatable imaging of lipophagy. Q-lipo with acidic pH activated near infrared fluorescence and the lipid droplet targeting ability allowed activatable fluorescence imaging and flow cytometry detection of lipophagy in live cells with high contrast. It was further utilized to study the effect of tumor-microenvironment related conditions on lipophagy. Q-lipo would provide a useful tool for studying lipophagy in live cells.
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http://dx.doi.org/10.1039/d1cc03259cDOI Listing
September 2021

Construction of Mode of Action for Cadmium-Induced Renal Tubular Dysfunction Based on a Toxicity Pathway-Oriented Approach.

Front Genet 2021 23;12:696892. Epub 2021 Jul 23.

Department of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou, China.

Although it is recognized that cadmium (Cd) causes renal tubular dysfunction, the mechanism of Cd-induced nephrotoxicity is not yet fully understood. Mode of action (MOA) is a developing tool for chemical risk assessment. To establish the mechanistic MOA of Cd-induced renal tubular dysfunction, the Comparative Toxicogenomics Database (CTD) was used to obtain genomics data of Cd-induced nephrotoxicity, and Ingenuity Pathway Analysis (IPA) software was applied for bioinformatics analysis. Based on the perturbed toxicity pathways during the process of Cd-induced nephrotoxicity, we established the MOA of Cd-induced renal tubular dysfunction and assessed its confidence with the tailored Bradford Hill criteria. Bioinformatics analysis showed that oxidative stress, DNA damage, cell cycle arrest, and cell death were the probable key events (KEs). Assessment of the overall MOA of Cd-induced renal tubular dysfunction indicated a moderate confidence, and there are still some evidence gaps to be filled by rational experimental designs.
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http://dx.doi.org/10.3389/fgene.2021.696892DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8343180PMC
July 2021
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