Publications by authors named "Jian Xu"

2,762 Publications

  • Page 1 of 1

Engineering rotating apical-out airway organoid for assessing respiratory cilia motility.

iScience 2022 Aug 9;25(8):104730. Epub 2022 Jul 9.

Department of Biomedical Engineering, Carnegie Mellon University, 5000 Forbes Avenue, Pittsburgh, PA, USA.

Motile cilia project from the airway apical surface and directly interface with inhaled external environment. Owing to cilia's nanoscale dimension and high beating frequency, quantitative assessment of their motility remains a sophisticated task. Here we described a robust approach for reproducible engineering of apical-out airway organoid (AOAO) from a defined number of cells. Propelled by exterior-facing cilia beating, the mature AOAO exhibited stable rotational motion when surrounded by Matrigel. We developed a computational framework leveraging computer vision algorithms to quantify AOAO rotation and correlated it with the direct measurement of cilia motility. We further established the feasibility of using AOAO rotation to recapitulate and measure defective cilia motility caused by chemotherapy-induced toxicity and by CCDC39 mutations in cells from patients with primary ciliary dyskinesia. We expect our rotating AOAO model and the associated computational pipeline to offer a generalizable framework to expedite the modeling of and therapeutic development for genetic and environmental ciliopathies.
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http://dx.doi.org/10.1016/j.isci.2022.104730DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9356180PMC
August 2022

Postoperative Long-Term Outcomes and Independent Risk Factors of Non-Small-Cell Lung Cancer Patients With Propofol versus Sevoflurane Anesthesia: A Retrospective Cohort Study.

Front Pharmacol 2022 22;13:945868. Epub 2022 Jul 22.

Department of Anesthesiology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.

Existing studies have shown that the relationship between anesthetic agents and non-small-cell lung cancer (NSCLC) prognosis remains controversial. Therefore, this retrospective cohort study was designed to investigate the effects of propofol or sevoflurane anesthesia on the long-term oncologic outcomes of NSCLC patients. We identified 1,778 eligible patients (propofol-based total intravenous anesthesia (TIVA) group, = 686; sevoflurane-based inhalation anesthesia (INHA) group, = 1,092) out of 2,388 patients undergoing elective NSCLC surgery from June 2013 to June 2016 in the Harbin Medical University Cancer Hospital. The primary endpoints were five-year overall survival and recurrence-free survival. The secondary endpoints were independent risk factors of cancer recurrence or all-cause mortality. The data were analyzed with propensity score matching, Kaplan-Meier survival, and Cox multivariate analyses as appropriate. After propensity score matching, there were 672 patients in each group. The median follow-up period was 69 months (interquartile range: 68-70 months) for all patients. Five-year overall survival was 75.7% (95% confidence interval (CI) 72.4-79.1) in the TIVA group and 71.8% (68.4-75.4) in the INHA group ( = 0.160) (hazard ratio (HR), 0.86; 95% CI, 0.70-1.06; = 0.158), and five-year recurrence-free survival was 68.5% (65.0-72.2) and 62.7% (59.1-66.5 ( = 0.108) (HR, 0.90; 95% CI, 0.75-1.08; = 0.253), respectively. Subgroup analyses showed there were no significant difference in the overall survival or recurrence-free survival between the two groups in each TNM stage of NSCLC. The independent risk factors included age ≥60 years, male, blood transfusion, segmental/wedge resection and pneumonectomy, thoracotomy, postoperative complications, lung adenocarcinoma, TNM stages, high CEA and CYFRA211 levels, and postoperative radiotherapy. Our data indicated no difference between the propofol-based TIVA and sevoflurane-based INHA in terms of five-year overall survival and recurrence-free survival after NSCLC surgery.
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http://dx.doi.org/10.3389/fphar.2022.945868DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9354745PMC
July 2022

Human activities induce potential aquatic threats of micropollutants in Danjiangkou Reservoir, the largest artificial freshwater lake in Asia.

Sci Total Environ 2022 Aug 4:157843. Epub 2022 Aug 4.

College of Environmental Science and Engineering, Tongji University, Shanghai 200092, China; State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012, China. Electronic address:

Freshwater biodiversity and ecosystem services may decline because of toxicant input, and other environmental variables often co-occur with contaminants to jeopardize the freshwater ecosystem. In this study, Danjiangkou Reservoir (DJKR) in central China was selected as the target research area to investigate the impact of multiple categories of micropollutants coupled with other stressors on the reservoir ecosystem. A total of 140 samples were collected from 28 sites in DJKR, and 124 micropollutants, including pesticides, organophosphate esters (OPEs), psychoactive substances, antiviral drugs, and pharmaceutical and personal care products, were quantified. A total of 108 micropollutants were detected in the water samples, with sum concentrations ranging from 82.35 ng·L to 1436.57 ng·L, and 71 of them had a detection frequency above 50 %, indicating the prevailing micropollutant contamination in the reservoir. The most severe pollution and risks were observed in the tributaries of DJKR. Pesticides (neonicotinoid and triazine) and OPEs were the major contributors to the ecological risk in the reservoir. Insecticides, herbicides, and OPEs accounted for the majority of the risks to fish, algae, and invertebrates, respectively. The determined priority pollutants should be paid increased attention. Environmental variables and human activities, such as human land use, induced the potential aquatic threats of micropollutants in DJKR. Results demonstrated that micropollutant pollution was one of the dominant pressures faced by aquatic organisms and human beings, and human activities played important roles as well.
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http://dx.doi.org/10.1016/j.scitotenv.2022.157843DOI Listing
August 2022

Occurrence, distribution, and ecological risk of psychoactive substances in typical lakes and rivers in Qinghai-Tibet Plateau.

Ecotoxicol Environ Saf 2022 Aug 1;242:113928. Epub 2022 Aug 1.

State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012, China; Center for Environmental Health Risk Assessment and Research, Chinese Research Academy of Environmental Sciences, Beijing 100012, China; State Environmental Protection Key Laboratory of Ecological Effect and Risk Assessment of Chemicals, Chinese Research Academy of Environmental Sciences, Beijing 100012, China. Electronic address:

The occurrence, distribution, and ecological risks of psychoactive substances (PSs) in Qinghai-Tibet Plateau (QTP) was investigated in this study. The surface water samples were collected in July in 2020 from five major water bodies, and 9 PSs were determined by liquid chromatography-mass spectrometry. The mean concentrations of the total PSs were 2.19-96.86 ng/L in lakes and 4.56-34.47 ng/L in rivers. Amphetamine (AMP) was the predominant contaminant both in lakes and rivers with a mean concentration of 12.21 ± 22.76 ng/L and 9.83 ± 6.14 ng/L, respectively. The compositions of PSs in lakes and rivers were significantly different. AMP, methadone (MTD), 3,4-methylenedioxyamphetamine (MDA), and ketamine (KET) were the most detected contaminants in lakes, while in rivers AMP, MDA, heroin (HER), and methamphetamine (METH) were the most detected ones. Concentrations of AMP and MTD, the two predominant drugs, varied spatially, with the decreasing concentration of AMP in the order of Huangshui River > Yamzhog Yumco Lake > Qinghai Lake > Lhasa River > Namco Lake, and of MTD in the order of Qinghai Lake > Namco Lake > Huangshui River > Yamzhog Yumco Lake. The risk quotients (RQs) of PSs ranged from 4.44 × 10 to 4.32 × 10, indicating a low risk of PSs in the aquatic ecosystem in QTP. Compared with other research in the world, the contamination of psychoactive substances in the Qinghai-Tibet Plateau was at relatively low levels with low ecological risks.
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http://dx.doi.org/10.1016/j.ecoenv.2022.113928DOI Listing
August 2022

Isolation of Monocyte-Macrophage Lineage Cells from Rat Bones by Secondary Adherence Method.

J Vis Exp 2022 Jul 13(185). Epub 2022 Jul 13.

School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University;

With a decrease of bone mineral density, bones are more likely to fracture, thus negatively affecting a patient's quality of life. The growth and development of bones are mainly regulated by osteoblasts and osteoclasts. It has been widely accepted that osteoclasts are derived from bone marrow monocyte-macrophage cells (BMMs). BMMs and other hematopoietic stem cells are located in the bone marrow cavity. Therefore, isolating single stable BMMs from different and heterogeneous cell populations is a huge challenge. Here we present a protocol for the isolation of BMMs from SD rats, called the secondary adherence method. Adherent cells cultured for 24-48 h in primary culture were collected. Flow cytometric analysis showed that approximately 37.94% of the cells were CD11b/c+ (monocyte-macrophage surface antigen). Tartrate resistant acid phosphatase (TRAP) staining and western blot analysis demonstrated that BMMs could differentiate into osteoclasts in vitro. The above findings suggested that the secondary adherence cells could be considered as a suitable cellular model for osteoclast differentiation research.
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http://dx.doi.org/10.3791/64053DOI Listing
July 2022

Diagnostic Value of Multimodal Magnetic Resonance Imaging in Discriminating Between Metastatic and Non-Metastatic Pelvic Lymph Nodes in Cervical Cancer.

Int J Gen Med 2022 22;15:6279-6288. Epub 2022 Jul 22.

Department of Radiology, Ningbo Women & Children's Hospital, Ningbo, People's Republic of China.

Background: The status of pelvic lymph node (PLN) metastasis affects treatment and prognosis plans in patients with cervical cancer. However, it is hard to be diagnosed in clinical practice.

Purpose: The present study aimed to evaluate the diagnostic value of multimodal magnetic resonance imaging (MRI) in discriminating between metastatic and non-metastatic pelvic lymph nodes (PLNs) in cervical cancer.

Methods: This retrospective study analyzed MRIs of 209 PLNs in 25 women with pathologically proven cervical cancer. All PLNs had been assessed by pre-treatment multimodal MRIs, and their status was finally confirmed by histopathology. In conventional MRI, lymph node characteristics were compared between metastatic and non-metastatic PLNs. Signal intensity, time-intensity curve (TIC) patterns minimal and mean apparent diffusion coefficients (ADC) were compared between them in DWI. In DCE-MRI, quantitative (K, K and V) analyses were performed on DCE-MRI sequences, and their predictive values were analyzed by ROC curves.

Results: Of 209 PLNs, 22 (10.53%) were metastases and 187 (89.47%) were non-metastases at histopathologic examination. Considering a comparison of lymph node characteristics, the short axis size, the long axis size, and the boundary differed significantly between the two groups (<0.05).The differences in ADC, TIC types, K and V between metastatic and non-metastatic PLNs were significant as well (<0.05). The good diagnostic performance of multimodal MRI was shown in discriminating between metastatic and non-metastatic PLNs, with the sensitivity of 85.0% (17/20), specificity of 97.3% (184/189), and accuracy of 96.2% (201/209). ROC analyses showed that the diagnostic accuracy of ADC, K and V for discriminating between metastatic and non-metastatic PLNs in cervical cancer was 83.7%, 91.4%, and 92.4% with the cut-off values of 0.72 × 10mm/s, 0.52 min, and 0.53 min, respectively.

Conclusion: Multimodal MRI showed good diagnostic performance in determining PLN status in cervical cancer.
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http://dx.doi.org/10.2147/IJGM.S372154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9326496PMC
July 2022

The Association of Internet Use Intensity and Lifestyle Behaviors During the COVID-19 Pandemic: A Cross-Sectional Study in Chinese Adults.

Front Public Health 2022 13;10:934306. Epub 2022 Jul 13.

School of Media and Communication, Shanghai Jiao Tong University, Shanghai, China.

The COVID-19 pandemic substantially increased the intensity of internet use in humans, which has made public opinion around health and public perceptions of it more vital, and this phenomenon has had a significant impact on human lifestyle behavior. This study used cross-sectional data during the COVID-19 pandemic to explore how internet use intensity influenced lifestyle behaviors among adults, and compared the differences between samples of different ages. The findings showed that the internet use intensity among adults increased the probability of physical activity, staying up late, and high-quality eating behaviors, and that they had a statistically significant positive association. Such associations were also found in independent younger, middle-aged, and older samples. However, the internet use intensity elevated the probability of body weight gain only in the independent samples of younger, middle-aged, and older adults. Besides, internet use intensity was able to increase the probability of smoking & drinking only among the younger sample. Notably, the effect of internet use intensity on lifestyle behaviors, including body weight gain, physical activity, staying up late, and a high-quality diet, was strongest among the elderly, followed by the middle-aged, and weakest among the younger. In the process of rural and urban governance regarding citizens' health, public health agencies should remind citizens to spend a reasonable amount of time on internet use to reduce the probability of unhealthy lifestyle behaviors and improve their physical health.
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http://dx.doi.org/10.3389/fpubh.2022.934306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9326102PMC
August 2022

Customized whole brain-covering 3D GRASE in multi-delay pseudo-continuous arterial spin labeling for duplex distinct hemodynamic mapping contrasts of brain tissues and circulation pathways.

Phys Med Biol 2022 Jul 29. Epub 2022 Jul 29.

UIH America, Inc, 9230 Kirby Drive, Houston, 77054, UNITED STATES.

GRASE is widely employed in ASL as an efficient readout sequence. Hemodynamic parameter mappings of perfusion, such as CBF and ATT, can be derived via multi-delay ASL acquisitions. Multi-delay ASL perfusion imaging inevitably suffers limited SNR since a motion-sensitized vessel suppressing module has to be employed to highlight perfusion signals. The present work reveals that in multi-delay ASL, manipulation of GRASE sequence on either EPI echo train for adjusted spatial resolutions or FSE echo train for modulated extent of T-blurring can significantly alter the mapping contrasts among tissues and among cerebral lobes under different pathways of blood circulation, and meanwhile regulates SNR. Four separate multi-delay ASL scans with different echo train designs in 3D whole-brain covering GRASE were carried out for healthy subjects to evaluate the variations in regard to the parameter quantifications and SNR. Based on the quantification mappings, the GRASE acquisition with moderate spatial resolution (3.5×3.5×4 mm) and segmented kscheme is recognized for the first time to be recommended for more unambiguous CBF and ATT contrasts between GM and WM in conjunction with more enhanced ATT contrast between anterior and posterior cerebral circulations, with reasonably good SNR. The technical proposal is of great value for the cutting-edge research of a variety of neurological diseases of global concerns.
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http://dx.doi.org/10.1088/1361-6560/ac8591DOI Listing
July 2022

Association between obstructive sleep apnea (OSA) and atrial fibrillation (AF): A dose-response meta-analysis.

Medicine (Baltimore) 2022 Jul 29;101(30):e29443. Epub 2022 Jul 29.

Department of Cardiology, Xijing Hospital, The Air Force Military Medical University, Xi'an Shaanxi, China.Supplemental Digital Content is available for this article.

Background: Refractory hypoxemia episodes are characteristic of obstructive sleep apnea (OSA). Patients with OSA suffer from oxidative stress in all systems. Atrial fibrillation (AF) is a type of arrhythmia that may be induced by OSA. In this study, we explored the dose-response relationship between OSA and AF. Our research provides the basis for a novel approach to AF prevention.

Methods: We screened four databases (PubMed, Embase, the Cochrane Library, and Web of Science) for observational studies on OSA and AF. Studies were collected from database establishment to November 2020. We performed a traditional subgroup meta-analysis. Linear and spline dose-response models were applied to assess the association between the apnea-hypopnea index, an indicator of OSA severity, and the risk of AF. Review Manager version 5.3 software and Stata 16.0 were used for the analysis.

Results: Sixteen observational studies were included in the study. We excluded a study from the conventional meta-analysis. In the subgroup analysis, the odds ratios for new onset AF for no obvious reason, new onset AF after surgical operations, such as coronary artery bypass grafting, and AF after ablation treatment were 1.71 (95% CI 1.37-2.13, P < .05), 2.65 (95% CI 2.32-3.01, P < .05), and 2.93 (95% CI 2.47-3.49, P < .05), respectively. Linear dose-response meta-analysis results revealed that the risk of AF increased with increasing apnea-hypopnea index value.

Conclusion: Through dose-response meta-analysis, we found a potential dose-response relationship between OSA severity and the risk of AF. This relationship should be considered in interventions aimed at AF prevention in the future.
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http://dx.doi.org/10.1097/MD.0000000000029443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9333485PMC
July 2022

Development of a natural language processing algorithm to extract seizure types and frequencies from the electronic health record.

Seizure 2022 Jul 20;101:48-51. Epub 2022 Jul 20.

Department of Neurology, University of Michigan, Ann Arbor, MI, United States.

Objective: To develop a natural language processing (NLP) algorithm to abstract seizure types and frequencies from electronic health records (EHR).

Background: Seizure frequency measurement is an epilepsy quality metric. Yet, abstraction of seizure frequency from the EHR is laborious. We present an NLP algorithm to extract seizure data from unstructured text of clinic notes. Algorithm performance was assessed at two epilepsy centers.

Methods: We developed a rules-based NLP algorithm to recognize terms related to seizures and frequency within the text of an outpatient encounter. Algorithm output (e.g. number of seizures of a particular type within a time interval) was compared to seizure data manually annotated by two expert reviewers ("gold standard"). The algorithm was developed from 150 clinic notes from institution #1 (development set), then tested on a separate set of 219 notes from institution #1 (internal test set) with 248 unique seizure frequency elements. The algorithm was separately applied to 100 notes from institution #2 (external test set) with 124 unique seizure frequency elements. Algorithm performance was measured by recall (sensitivity), precision (positive predictive value), and F1 score (geometric mean of precision and recall).

Results: In the internal test set, the algorithm demonstrated 70% recall (173/248), 95% precision (173/182), and 0.82 F1 score compared to manual review. Algorithm performance in the external test set was lower with 22% recall (27/124), 73% precision (27/37), and 0.40 F1 score.

Conclusions: These results suggest NLP extraction of seizure types and frequencies is feasible, though not without challenges in generalizability for large-scale implementation.
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http://dx.doi.org/10.1016/j.seizure.2022.07.010DOI Listing
July 2022

Higher Levels of Urinary Thiocyanate, a Biomarker of Cruciferous Vegetable Intake, Were Associated With Lower Risks of Cardiovascular Disease and All-Cause Mortality Among Non-smoking Subjects.

Front Nutr 2022 5;9:919484. Epub 2022 Jul 5.

Hubei Key Laboratory of Food Nutrition and Safety, Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: Epidemiologic studies on cruciferous vegetable (CV) intake and cardiovascular disease (CVD) were inconclusive.

Objective: To investigate the associations of urinary thiocyanate, a biomarker of CV intake, with CVD and all-cause mortality among non-smoking adults.

Methods: This prospective cohort study comprised 10,489 non-smoking adults (weighted mean age, 46.8 years; 43.4% male) from the National Health and Nutrition Examination Survey 2001-2014. Non-smokers were defined as subjects with serum cotinine < 3 ng/mL. Urinary thiocyanate was measured with ion chromatography tandem mass spectrometry at baseline, and CVD and all-cause mortality were identified through linkage to National Death Index until December 31, 2015. Cox proportional hazards model was applied to estimate the hazard ratios (HRs) with 95% confidence intervals (CIs) for CVD and all-cause mortality.

Results: A total of 800 deaths, of which 136 died of CVD, were ascertained within a median 7.8 years of follow-up. Urinary thiocyanate was positively correlated with total CV intake among non-smoking adults ( = 0.088, < 0.001). Comparing extreme quartiles, the multivariate-adjusted HRs for CVD and all-cause mortality were 0.50 (95% CI: 0.29-0.85) and 0.75 (95% CI: 0.60-0.92), respectively. Each 1 μg/g creatinine increment of log-transformed urinary thiocyanate was associated with a 25% (HR: 0.75; 95% CI: 0.62-0.91) reduced CVD mortality risk and 12% (HR: 0.88; 95% CI: 0.81-0.96) reduced all-cause mortality risk. The documented inverse associations persisted in sensitivity analyses.

Conclusion: Increased levels of urinary thiocyanate, a candidate biomarker of CV intake, were associated with low risks of CVD and total mortality among non-smoking adults. This prospective biomarker-based study provided further evidence to support the cardiovascular benefits of CVs.
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http://dx.doi.org/10.3389/fnut.2022.919484DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9294399PMC
July 2022

A PtPdCoCuNi high-entropy alloy nanocatalyst for the hydrogenation of nitrobenzene.

RSC Adv 2022 Jul 7;12(31):19869-19874. Epub 2022 Jul 7.

School of Chemistry and Chemical Engineering, In-situ Center for Physical Sciences, Frontiers Science Center for Transformative Molecules, Shanghai Jiao Tong University Shanghai 200240 China

High-entropy alloys (HEAs) with multiple elements in near-equiatomic proportions hold great promise in heterogeneous catalysis because of their exceptional physicochemical properties governed by synergy. Herein, we prepared PtPdCoCuNi HEA nanoparticles a one-step colloid-based route and tested their catalytic performance for nitrobenzene hydrogenation to aniline. The SiO supported PtPdCoCuNi displays 93.9% yield of aniline at 80 °C, which is 2.11 times that of PtPd/SiO. Even at room temperature, a 47.4% yield of aniline is attained with the PtPdCoCuNi/SiO catalyst. DRIFTS experiments indicate formation of isolated Pt and Pd sites after alloying the transition metals and evidence a stronger interaction between the HEA catalyst and nitrobenzene. Both XPS data and DFT calculations disclose charge transfer to Pt and Pd species, which eventually enhance the interaction between nitrobenzene and the isolated metal sites and the hydrogenation activity as well. The experimental and theoretical results shed light on mechanistic understanding of the unique catalytic performance of the HEA nanocatalyst and pave a new avenue to realize the high catalytic performance of nitrobenzene hydrogenation over well-isolated noble metal sites with specific geometries.
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http://dx.doi.org/10.1039/d2ra03145kDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9260516PMC
July 2022

Knockdown of Circ_0000798 Impedes Cell Growth and Motility of Renal Cell Carcinoma Cells Through Functioning as miRNA Sponge for miR-589-5p.

Biochem Genet 2022 Jul 20. Epub 2022 Jul 20.

Department of Urology Surgery, Yiwu City Center Hospital, No.699 Jiangdong Road, Yiwu, 322000, Zhejiang, China.

GSE137836 and GSE100186 shows that upregulated hsa_circRNA_0000798 (circ_0000798) is associated with the development and progression of renal cell carcinoma (RCC). However, its biological functions in RCC cells remain unclarified. Here, we planned to explore its action and action of mechanism in RCC cells. Real-time quantitative PCR detected RNA expression and western blotting and immunohistochemistry measured protein expression. In vitro assays, including MTT, EdU, Transwell, and plate colony, scratch wound, apoptosis, and cell cycle assays, and in vivo xenograft tumor model were launched to measure cell dysfunctions. Dual-luciferase reporter assay and RNA pull-down were employed to identify target relationship. Circ_0000798 is upregulated in RCC patients' tumors and cells, and high circ_0000798 is associated with shorter overall survival. RNA interference of circ_0000798 impedes cell metabolic viability and abilities of DNA synthesis, colony formation, wound healing, migration, and invasion in RCC cells but also induces cell cycle arrest and apoptosis. Moreover, circ_0000798 interference could delay tumor growth in vivo. Proliferation markers Ki67 and Bcl-2 were depressed by inhibiting circ_0000798, accompanied with promoted levels of apoptosis proteins Bax and cleaved caspase-3. Of note, circ_0000798 functions as microRNA (miR) sponge for miR-589-5p and thus controls the expression of miR-589-5p-targeting Ras-GTPase-activating protein-binding protein 1 (G3BP1), a newly identified tumor-promoting gene in RCC. Their expressions are linearly correlated with each other in these tumor samples. Circ_0000798 might function oncogenic role in RCC and its downregulation could combat RCC cell growth and motility via targeting miR-589-5p/G3BP1 axis.
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http://dx.doi.org/10.1007/s10528-022-10248-xDOI Listing
July 2022

The Heaviest Bottleable Metallylone: Synthesis of a Monatomic, Zero-Valent Lead Complex ("Plumbylone").

Angew Chem Int Ed Engl 2022 Jul 18:e202209442. Epub 2022 Jul 18.

Department of Chemistry: Metalorganics and Inorganic Materials, Technische Universität Berlin, Strasse des 17. Juni 115, Sekr. C2, 10623, Berlin, Germany.

The elusive plumbylone {[Si (Xant)Si ]Pb } 3 stabilized by the bis(silylene)xanthene chelating ligand 1, [Si (Xant)Si =PhC(NtBu) Si(Xant)Si(NtBu) CPh], and its isolable carbonyl iron complex {[Si (Xant)Si ]Pb Fe(CO) } 4 are reported. The compounds 3 and 4 were obtained stepwise via reduction of the lead(II) dibromide complex {[Si (Xant)Si ]PbBr } 2, prepared from the bis(silylene)xanthene 1 and PbBr , employing potassium naphthalenide and K Fe(CO) , respectively. While the genuine plumbylone 3 is rather labile even at -60 °C, its Pb →Fe(CO) complex 4 turned out to be relatively stable and bottleable. However, solutions of 4 decompose readily to elemental Pb and {[Si (Xant)Si ]Fe(CO) } 5 at 80 °C. Reaction of 4 with [Rh(CO) Cl] leads to the formation of the unusual dimeric [(OC) RhPb(Cl)Fe(CO) ] complex 6 with trimetallic Rh-Pb-Fe bonds. The molecular and electronic structures of 3 and 4 were established by Density Functional Theory (DFT) calculations.
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http://dx.doi.org/10.1002/anie.202209442DOI Listing
July 2022

Cardiac glycosides from the roots of Streblus asper Lour. with activity against Epstein-Barr virus lytic replication.

Bioorg Chem 2022 Oct 9;127:106004. Epub 2022 Jul 9.

School of Traditional Chinese Pharmacy, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China; Jiangsu Food and Pharmaceutical Science College, Huaian 223003, China. Electronic address:

Cardiac glycosides (CGs) show potential broad-spectrum antiviral activity by targeting cellular host proteins. Herein are reported the isolation of five new (1-5) and eight known (7-13) CGs from the roots of Streblus asper Lour. Of these compounds 1 and 7 exhibited inhibitory action against EBV early antigen (EA) expression, with half-maximal effective concentration values (EC) being less than 60 nM, and they also showed selectivity, with selectivity index (SI) values being 56.80 and 103.17, respectively. Preliminary structure activity relationships indicated that the C-10 substituent, C-5 hydroxy groups, and C-3 sugar unit play essential roles in the mediation of the inhibitory activity of CGs against EBV. Further enzyme experiments demonstrated that these compounds might inhibit ion pump function and thereby change the intracellular signal transduction pathway by binding to Na/K-ATPase, as validated by simulated molecular docking. This study is the first report that CGs can effectively limit EBV lytic replication, and the observations made in this study may be of value for lead compound development.
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http://dx.doi.org/10.1016/j.bioorg.2022.106004DOI Listing
October 2022

PIK3CB promotes oesophageal cancer proliferation through the PI3K/AKT/mTOR signalling axis.

Cell Biol Int 2022 Sep 16;46(9):1399-1408. Epub 2022 Jul 16.

Department of Thoracic Surgery, Chongqing University Cancer Hospital, Chongqing, China.

PIK3CB is abnormally expressed in various carcinomas and affects the proliferation, invasion and drug resistance of cancer cells. However, its role in oesophageal squamous cell carcinoma (ESCC) is still unclear. In this study, PIK3CB was found to be highly expressed in ESCC tissues and cells and positively correlated with the poor prognosis of ESCC. Silencing PIK3CB inhibited the proliferation of ESCC cells, arrested the cell cycle, and promoted apoptosis. Mechanistic studies showed that the tumour-promoting effect of PIK3CB was achieved through PI3K/AKT/mTOR signalling pathway activation. Moreover, the high PIK3CB expression level in ESCC may be closely associated with the hypomethylation status of the gene promoter. In conclusion, PIK3CB promotes ESCC by activating the PI3K/AKT/mTOR signalling axis. PIK3CB may be a potential target in ESCC.
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http://dx.doi.org/10.1002/cbin.11847DOI Listing
September 2022

Exposure to perfluoroalkyl substances and neurodevelopment in 2-year-old children: A prospective cohort study.

Environ Int 2022 Jul 7;166:107384. Epub 2022 Jul 7.

Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, China; School of Public Health, Shanghai Jiao Tong University School of Medicine, 227 South Chongqing Road, Shanghai 200052, China. Electronic address:

Background: Humans are widely exposed to per- and polyfluoroalkyl substances (PFAS). As fetal stage is a critical window for neurodevelopment, it is important to know if in utero exposure to PFAS affects fetal neurodevelopment. However, previous human studies are both limited and inconsistent.

Objectives: To investigate the relationship between PFAS exposure during early pregnancy and the neurodevelopmental status at 2 years of age in a prospective cohort study.

Methods: We measured 10 PFAS in maternal plasma samples collected prior to 16 weeks of gestation in the Shanghai Birth Cohort Study between 2013 and 2016. Childhood neurodevelopment was assessed at 2 years of age using the Bayley Scales of Infant and Toddler Development-Third Edition (BSID-III). Associations with domain specific scores for individual PFAS were assessed by multiple linear regression and binary logistic regression when scores were dichotomized. Quantile-based g-computation was used to estimate the joint effects of PFAS mixture.

Results: A total of 2257 mother-child pairs who had both PFAS and BSID measurements were included in our analyses. The means and standard deviations of comprehensive scores were 115 ± 22, 96 ± 15 and 108 ± 15 for cognition, language, and motor, respectively. In multiple linear regressions, we observed significant negative associations of perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDeA), perfluoroundecanoic acid (PFUnDA) with cognitive scores; PFNA, PFDeA, PFUnDA and perfluorohexanesulfonate (PFHxS) negatively with language scores; and PFNA and PFUnDA negatively with motor scores. Quantile-based g-computation showed that PFAS mixture was significantly associated with decreased cognitive and language scores, with an estimated β of -2.1 [95% confidence interval (CI): -3.5, -0.7)] and -2.0 (95% CI: -2.9, -1.0) per one quartile increase in PFAS mixture for cognitive and language domains, respectively. PFAS mixture was associated with increased odds of low cognition (adjusted odds ratio [OR] = 1.3, 95% CI:1.0, 1.6) and language scores (OR = 1.2, 95% CI: 1.1, 1.3).

Conclusions: PFAS exposure during early pregnancy was significantly associated with the adverse neurodevelopmental status at 2 years of age, which raises a serious public health concern.
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http://dx.doi.org/10.1016/j.envint.2022.107384DOI Listing
July 2022

Aortic valve opening in mock-loop with continuous-flow left ventricular assist device.

Int J Artif Organs 2022 Jul 11:3913988221111811. Epub 2022 Jul 11.

School of Medicine, Tsinghua University (School of Medicine) - RocketHeart Co. Ltd Joint Research Center for Artificial Heart, Tsinghua University, Beijing, China.

The appropriate opening of aortic valves is crucial for heart failure (HF) patients with left ventricular assist devices (LVADs). Nevertheless, up to the present time, aortic valve monitoring has not been performed in discharged patients. In this study, a mock-loop platform was developed to investigate the aortic valve performance in LVAD patients. An additional sluice valve was placed next to the aortic valve that when the sluice valve is manually closed, the aortic valve will remain closed; when the sluice valve is open, the aortic valve is opened or closed upon the pressures. The results showed that when the LVAD speed was below 2600 rpm, the aortic valve can be intermittently opened, while when the LVAD speed was over 2600 rpm, the aortic valve was persistently closed. The left ventricular end-systolic pressure (LVESP) was found to be an indicator of aortic valve closure that, upon the aortic valve closure LVESP suddenly decreased. The LVESP is suggested for future monitoring the status of the aortic valve for patients with implanted LVADs. The effects of heart failure (HF) degrees, circulation resistance, and aortic compliance on aortic valve closure were further studied. The results revealed that LVAD implantation in patients with early HF degrees will help to avoid persistent aortic valve closure.
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http://dx.doi.org/10.1177/03913988221111811DOI Listing
July 2022

Family Socioeconomic Status and Internalizing Problem Behavior Among Chinese Adolescents: The Chain Mediation Effect of Academic Performance and Peer Conflict.

Front Psychol 2022 23;13:902545. Epub 2022 Jun 23.

China Institute for Urban Governance, Shanghai Jiao Tong University, Shanghai, China.

This study aims to provide a new perspective on the relationship between family socioeconomic status (SES) and internalizing problem behavior (IPB) among adolescents. Many studies have focused on the relationship between family SES and IPB among adolescents; however, research on the underlying mechanism is still insufficient, and peer conflict has been ignored as a crucial social relationship factor for adolescents. This study identifies two new mediating variables and a chain mediating mechanism model between them. Using national longitudinal data from 2,467 adolescents aged 10-15 published in the China Family Panel Studies of wave 2018, this study found the following: (1) higher family SES can significantly reduce peer conflict and IPB among adolescents; (2) adolescents with better academic performance were less likely to be involved in peer conflict; (3) peer conflict mediated 30.41% of the relationship between family SES and adolescent's IPB; and (4) there was a chain mediating mechanism, and the mediating effect of peer conflict was much stronger than the mediating effect of both academic performance and the chain mediation pathways. This is the first study to develop a chain mediation model to examine the roles of academic achievement and peer conflict in the relationship between family SES and IPB. These findings are significant in that they highlight the importance of providing adolescents with proper emotional de-escalation and peer conflict resolution strategies, contributing to the management of adolescent mental health in urban governance and rural development.
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http://dx.doi.org/10.3389/fpsyg.2022.902545DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9260152PMC
June 2022

Platelet-to-Portal Vein Width Ratio and Platelet-to-Spleen Thickness Ratio Can Be Used to Predict Progressive Liver Fibrosis Among Patients With HBV Infection With HBeAg-Negativity and a Normal ALT Level.

Front Med (Lausanne) 2022 21;9:837898. Epub 2022 Jun 21.

Department of Infectious Disease, The People's Hospital of Yubei District of Chongqing City, Chongqing, China.

Background: Some people infected with the hepatitis B virus (HBV) with a normal level of alanine aminotransferase (ALT) are at risk of disease progression. We evaluated the value of platelet-to-portal vein width ratio (PPR) and platelet-to-spleen thickness ratio (PSR) to predict progressive liver fibrosis among patients with HBV infection with HBV e antigen (HBeAg)-negativity and a normal ALT level.

Methods: HBV surface antigen (HBsAg)-positive and HBeAg-negative individuals with a normal ALT level were enrolled. The inflammation grade (G) and fibrosis stage(S) were analyzed according to pathological features. Then, two groups (
Results: Seventy-three individuals among 142 patients with HBsAg-positivity and HBeAg-negativity had a normal ALT level. Also, 83.56% (61/73) individuals showed progressive liver fibrosis (≥S2). The ALT level and aspartate aminotransferase (AST) between the two groups differed (21.01 ± 7.40 vs. 25.37 ± 7.90 U/L, = 0.08; 29.49 ± 13.56 vs. 30.16 ± 21.88 U/L, = 0.92, respectively). Portal-vein width, serum levels of albumin and globulin, AST-to-Platelet Ratio Index (APRI), and Fibrosis 4 (FIB-4) score were not significantly different between the two groups ( > 0.05). The platelet count, PPR, and PSR were significantly different between the two groups [(145.92 ± 14.55) ×10/L vs. (126.38 ± 23.85) ×10/L, = 0.008; 10.80 ± 1.30 vs. 9.01 ± 1.97, = 0.004; 4.21 ± 0.65 vs. 3.33 ± 0.89, = 0.02, respectively]. The PPR and PSR decreased gradually upon fibrosis aggravation ( < 0.05). Based on the cut off value of the PPR (9.07) and PSR (3.54), their sensitivity and specificity was 0.917 and 0.525, and 0.833 and 0.541, respectively.

Conclusion: The PPR and PSR can be employed to assess earlier fibrosis progression among patients with HBV infection with HBeAg-negativity and a normal ALT level.
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http://dx.doi.org/10.3389/fmed.2022.837898DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9253570PMC
June 2022

Prevalence and risk of atrial fibrillation in China: A national cross-sectional epidemiological study.

Lancet Reg Health West Pac 2022 Jun 11;23:100439. Epub 2022 Apr 11.

The Second Hospital of Hebei Medical University, Shijiazhuang 050004, China.

Background: Atrial fibrillation (AF) is the most common persistent cardiac arrhythmia. This study aimed to estimate its prevalence and explore associated factors in adults aged 18 years or older in China.

Methods: Study data were derived from a national sample from July 2020 to September 2021. Participants were recruited using a multistage stratified sampling method from twenty-two provinces, autonomous regions, and municipalities in China. AF was determined based on a history of diagnosed AF or electrocardiogram results.

Findings: A total of 114,039 respondents were included in the final analysis with a mean age of 55 years (standard deviation 17), 52·1% of whom were women. The crude prevalence of AF was 2·3% (95% confidence interval [CI] 1·7-2·8) and increased with age. The age-standardized AF prevalence was 1·6% (95% CI 1·6-1·7%) overall, and 1·7% (1·6-1·8%), 1·4% (1·3-1·5%), 1·6% (95% CI 1·5-1·7%), and 1·7% (1·6-1·9%) in men, women, urban areas, and rural areas, respectively. The prevalence was higher in the central regions (2·5%, 2·3-2·7%) than in the western regions (1·5%, 1·0-2·0%) and eastern regions (1·1%, 1·0-1·2%) in the overall population, either in the gender or residency subgroups. The associated factors for AF included age (per 10 years; odds ratio 1·41 [95% CI 1·38-1·46];  < 0·001), men (1·34 [1·24-1·45];  < 0·001), hypertension (1·22 [1·12-1·33];  < 0·001), coronary heart disease (1·44 [1·28-1·62];  < 0·001), chronic heart failure (3·70 [3·22-4·26];  < 0·001), valvular heart disease (2·13 [1·72-2·63];  < 0·001), and transient ischaemic attack/stroke (1·22 [1·04-1·43];  = 0·013).

Interpretation: The prevalence of AF was 1.6% in the Chinese adult population and increased with age, with significant geographic variation. Older age, male sex, and cardiovascular disease were potent factors associated with AF. It is crucial to increase the awareness of AF and disseminate standardized treatment in clinical settings to reduce the disease burden.

Funding: This research was supported the Nature Science Foundation of Hubei province (No: 2017CFB204).
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http://dx.doi.org/10.1016/j.lanwpc.2022.100439DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9252928PMC
June 2022

Carbon Nanotubes Grown on the Carbon Fibers to Enhance the Photothermal Conversion toward Solar-Driven Applications.

ACS Appl Mater Interfaces 2022 Jul 7;14(28):32404-32411. Epub 2022 Jul 7.

Institute of Low-Dimensional Materials Genome Initiative, College of Chemistry and Environmental Engineering, Shenzhen University, Shenzhen 518060, China.

Photothermal conversion is a directly, sustainable, and green path to use solar energy and the one of the most important keys is the photothermal conversion material. How to obtain the durable and effective material for photothermal conversion with low cost and facile preparation is still a great challenge. In this work, the carbon nanotubes (CNTs) are grown on the carbon fibers (CFs) via the catalysis of trapped Fe and Co. The absorption of the as-prepared CFs/CNTs illustrate the enhancement from the visible light to the near-infrared light range. The photothermal conversion characterization shows the grown CNTs promoting the higher surface temperature and the highest temperature reaches to about 325 °C under 10 sun irradiations. The water evaporation on the CFs/CNTs is measured 1.40 ± 0.03 kg·cm·h under 1 sun irradiation and the water evaporation rate is also found depending on the irradiation density. The photothermal conversion applications and the water evaporation under natural irradiation also reveal the suitable candidate of the CFs/CNTs for photothermal conversion application. This work provides a facile path to obtain effective carbon-based materials for photothermal application.
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http://dx.doi.org/10.1021/acsami.2c07970DOI Listing
July 2022

Intersectional mapping of multi-transmitter neurons and other cell types in the brain.

Cell Rep 2022 Jul;40(1):111036

Departments of Ophthalmology and Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Department of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA. Electronic address:

Recent developments in intersectional strategies have greatly advanced our ability to precisely target brain cell types based on unique co-expression patterns. To accelerate the application of intersectional genetics, we perform a brain-wide characterization of 13 Flp and tTA mouse driver lines and selected seven for further analysis based on expression of vesicular neurotransmitter transporters. Using selective Cre driver lines, we created more than 10 Cre/tTA combinational lines for cell type targeting and circuit analysis. We then used VGLUT-Cre/VGAT-Flp combinational lines to identify and map 30 brain regions containing neurons that co-express vesicular glutamate and gamma-aminobutyric acid (GABA) transporters, followed by tracing their projections with intersectional viral vectors. Focusing on the lateral habenula (LHb) as a target, we identified glutamatergic, GABAergic, or co-glutamatergic/GABAergic innervations from ∼40 brain regions. These data provide an important resource for the future application of intersectional strategies and expand our understanding of the neuronal subtypes in the brain.
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http://dx.doi.org/10.1016/j.celrep.2022.111036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9290751PMC
July 2022

Correction to: Calculating glenoid bone loss based on glenoid height using ipsilateral three-dimensional computed tomography.

Knee Surg Sports Traumatol Arthrosc 2022 Jul 6. Epub 2022 Jul 6.

Division of Orthopaedic Surgery, Faculty of Medicine, Dalhousie University, Halifax, NS, Canada.

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http://dx.doi.org/10.1007/s00167-022-07055-7DOI Listing
July 2022

The efficiency of a clinical pathway to guide combined applications of interventional pulmonology in undiagnosed pleural effusions.

Sci Rep 2022 Jul 1;12(1):11126. Epub 2022 Jul 1.

Department of Pathology, Dalian Municipal Central Hospital Affiliated of Dalian Medical University, Dalian, 116033, China.

The diagnostic procedure of pleural effusion (PEs) is challenging due to low detection rates and numerous aetiologies. Hence, any attempt to enhance diagnosis is worthwhile. We present a clinical pathway to guide combined application of interventional pulmonology (IP) for tracing causes of undiagnosed PEs. Subjects with undiagnosed PEs were identified in the Hospital Information System of Dalian Municipal Central Hospital from January 1, 2012, to December 31, 2018. Eligible subjects were divided into a group of combined tests and a group of medical thoracoscopy (MT). Optimal and subsequent diagnostic tests were performed depending on the guidance of the clinical pathway by matching profitable chest lesions with the respective adaptation. As the guidance of clinical pathway, common bronchoscopy would be preferentially selected if pulmonary lesions involved or within the central bronchus, EBUS-TBNA was favoured when pulmonary lesions were adjacent to the central bronchus or with the enlarged mediastinal/hilar lymph nodes, guided bronchoscopy would be preferred if pulmonary nodules/masses were larger than 20 mm with discernible bronchus signs, CT-assisted transthoracic core biopsy was preferred if pulmonary nodules were less than 20 mm, image guided cutting needle biopsy was the recommendation if the pleural thickness was larger than 10 mm and pulmonary lesions were miliary. MT was preferred only when undiagnosed PEs was the initial symptom and pulmonary lesions were miliary or absent. A total of 83.57% cases of undiagnosed PEs were eligible for the clinical pathway, and 659 and 216 subjects were included in the combined tests and MT groups, respectively, depending on the optimal recommendation of the clinical pathway. The total diagnostic yields in the combined tests and MT groups were 95.99% and 91.20%, respectively, and the difference in total diagnostic yield was statistically significant (χ = 7.510, p = 0.006). Overall, clinical pathway guidance of the combined application of IP is useful for tracing the causes of undiagnosed PEs. The diagnostic yield of undiagnosed PEs is significantly increased compared with that of MT alone.
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http://dx.doi.org/10.1038/s41598-022-15454-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9249795PMC
July 2022

The "Deep Subarcuate Fossa" sign and three types of anomalous subarcuate loops encountered during vestibular schwannoma removal.

Acta Neurochir (Wien) 2022 Jul 1. Epub 2022 Jul 1.

Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.

Background: An anomalous subarcuate loop (SL) of the anteroinferior cerebellar artery (AICA) is a rare anatomic variation, which increases the complexity and risk of vestibular schwannoma (VS) removal. However, preoperative diagnosis of this anomaly remains difficult. The aim of this study was to report three types of anomalous SLs encountered during VS removal and to describe the "Deep Subarcuate Fossa (SF)" sign and its significance in the diagnosis and treatment of an osseous-penetrating SL.

Methods: We prospectively observed 963 patients with newly/recently diagnosed VS who underwent surgical treatment performed by the senior author (P.Z.) from 2012 to 2021 and identified 16 patients with an anomalous SL. The SF was retrospectively measured on preoperative thin-slice temporal bone computed tomography in 963 patients.

Results: Three types of anomalous SLs were encountered during VS removal: the apex of the SL was embedded in the dorsal tumor capsule (type I, 1 case), the dura (type II, 8 cases), or the dura and bone (type III, 7 cases) surrounding the SF. The depth of the SF in 7 patients with a type III anomalous SL ranged from 2.3 to 7.0 mm (3.56 ± 1.56 mm), which was significantly larger than that in 845 patients without an osseous-penetrating SL (1.23 ± 0.43 mm) (p = 0.008). When the depth of the SF exceeded 2 mm, the sensitivity and precision of the diagnosis of a type III anomalous SL were 100% (7/7) and 31.8% (7/22), respectively.

Conclusion: Three types of anomalous SLs may be encountered during VS removal, and AICA displacement is recommended before tumor removal. The "Deep SF" sign may indicate the existence of a type III anomalous SL and it can predict the depth of the AICA in the bone and guide the drilling of the bone around the vessel loop.
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http://dx.doi.org/10.1007/s00701-022-05288-6DOI Listing
July 2022

SETDB1 acts as a topological accessory to Cohesin via an H3K9me3-independent, genomic shunt for regulating cell fates.

Nucleic Acids Res 2022 07;50(13):7326-7349

Cell Fate Engineering and Therapeutics Lab, Cell Biology and Therapies Division, A*STAR Institute of Molecular and Cell Biology, Singapore 138673, Singapore.

SETDB1 is a key regulator of lineage-specific genes and endogenous retroviral elements (ERVs) through its deposition of repressive H3K9me3 mark. Apart from its H3K9me3 regulatory role, SETDB1 has seldom been studied in terms of its other potential regulatory roles. To investigate this, a genomic survey of SETDB1 binding in mouse embryonic stem cells across multiple libraries was conducted, leading to the unexpected discovery of regions bereft of common repressive histone marks (H3K9me3, H3K27me3). These regions were enriched with the CTCF motif that is often associated with the topological regulator Cohesin. Further profiling of these non-H3K9me3 regions led to the discovery of a cluster of non-repeat loci that were co-bound by SETDB1 and Cohesin. These regions, which we named DiSCs (domains involving SETDB1 and Cohesin) were seen to be proximal to the gene promoters involved in embryonic stem cell pluripotency and lineage development. Importantly, it was found that SETDB1-Cohesin co-regulate target gene expression and genome topology at these DiSCs. Depletion of SETDB1 led to localized dysregulation of Cohesin binding thereby locally disrupting topological structures. Dysregulated gene expression trends revealed the importance of this cluster in ES cell maintenance as well as at gene 'islands' that drive differentiation to other lineages. The 'unearthing' of the DiSCs thus unravels a unique topological and transcriptional axis of control regulated chiefly by SETDB1.
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http://dx.doi.org/10.1093/nar/gkac531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9303280PMC
July 2022

Huangqi Guizhi Wuwu Decoction can prevent and treat oxaliplatin-induced neuropathic pain by TNFα/IL-1β/IL-6/MAPK/NF-kB pathway.

Aging (Albany NY) 2022 06 27;14(12):5013-5022. Epub 2022 Jun 27.

Department of Colorectal Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang 110042, Liaoning Province, P.R. China.

Objective: This study explored the effects and mechanisms of Huangqi Guizhi Wuwu Decoction on chemotherapy-induced neuropathic pain (CINP).

Methods: Bodyweight and related behavioral testing of the rat model were utilized to investigate the effects of Huangqi Guizhi Wuwu Decoction on CINP. ELISA was used to measure the levels of TNF-α, IL-1β, and IL-6, in the serum of chronic CINP rats. Immunohistochemistry and Western blot analysis were performed to detect the expression of MAPK pathway related-proteins namely ERK1/2, p38, and JNK, and the expression of downstream essential proteins such as c-Fos, CREB, and NF-κB.

Results: Body weight and related behavioral testing of the rat model suggests that Huangqi Guizhi Wuwu Decoction can improve the slow weight gain of oxaliplatin-induced chronic CINP model rats and effectively prevent and treat oxaliplatin-induced regular CIPN rat model of hyperalgesia. It can also oppress the mechanical pain threshold, cold pain threshold, and heat pain threshold decreased. Furthermore, by ELISA, immunohistochemistry, and western blot analysis, we found that Huangqi Guizhi Wuwu Decoction can down-regulate the levels of TNF-α, IL-1β, and IL-6 in the serum of chronic CINP rats induced by oxaliplatin. It also suppresses the expression of MAPK pathway related-proteins ERK1/2, p38, and JNK. This results in a decrease in the expression of downstream essential proteins, c-Fos, CREB, and Nf-κB.

Conclusions: In conclusion, we found that Huangqi Guizhi Wuwu Decoction can combat nerve cell injury, reduce pain sensitization, and prevent and repair the damage of nerve cells in the oxaliplatin CINP model rats via TNFα/IL-1β/IL-6/MAPK/NF-kB pathway.
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http://dx.doi.org/10.18632/aging.203794DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9271291PMC
June 2022

Effects of single and combined exposure to lead and stress during pregnancy on offspring neurodevelopment.

Dev Cogn Neurosci 2022 Aug 16;56:101124. Epub 2022 Jun 16.

MOE-Shanghai Key Lab of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.

Objective: To assess associations of single and combined exposures to lead and stress during different stages of pregnancy with offspring neurodevelopment.

Methods: We measured prenatal lead (maternal blood-lead in early-pregnancy and umbilical-cord-blood-lead) and maternal stress levels in Shanghai-Birth-Cohort from 2013 to 2016. Maternal stress was assessed using Center-for-Epidemiological-Studies-Depression-Scale and Self-Rating-Anxiety-Scale during mid-pregnancy. The Ages-Stages-Questionnaires-3 (at 6/12-months-of-age) and Bayley-III (at 24-months-of-age) were both used to assess neurodevelopment.

Results: A total of 2132 mother-child pairs with both prenatal lead and stress measurements were included. The geometric-means of blood-lead in early-pregnancy and cord-blood-lead were 1.46 μg/dL and 1.33 μg/dL, respectively. Among the study women, 1.89 % and 0.14 % were screened positive for depression and anxiety. Adjusting for related confounders, the combined exposures had stronger adverse associations with offspring social-emotional skills than single exposures; and the combined exposure in early-pregnancy was associated with greater neurodevelopmental differences than combined exposure around-birth, especially in social-emotion at 24 months-of-age [β (95 %CI): - 10.48(-17.42, -3.54) vs. - 5.95(-11.53, -0.36)].

Conclusions: Both single and combined prenatal exposures to lead/stress impaired infant neuro-development, and the effects of combined exposure may be more profound than single exposures. Combined exposure in early-pregnancy may be associated with worse neurodevelopmental outcomes than combined exposure around-birth, especially in social-emotional development.
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http://dx.doi.org/10.1016/j.dcn.2022.101124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9243049PMC
August 2022

Increased blood-brain barrier permeability of the thalamus and the correlation with symptom severity and brain volume alterations in schizophrenia patients.

Biol Psychiatry Cogn Neurosci Neuroimaging 2022 Jun 20. Epub 2022 Jun 20.

Department of Rheumatology, First Affiliated Hospital of Kunming Medical University, Kunming, China, 650032. Electronic address:

Background: Cumulative evidence of microvascular dysfunction has suggested the blood-brain barrier (BBB) disruption in schizophrenia, while the direct in vivo evidence from patients is inadequate. In this study, using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) methods, we tried to test the hypothesis that there was increased BBB permeability in schizophrenia patients, and correlated with the clinical characters, and brain volumetric alterations.

Methods: Structural MRI and DCE-MRI data from 29 schizophrenia patients and 18 age- and sex- matched controls (HC) were obtained. We calculated the volume transfer constant (K) value and compared the difference between two groups. The regions with the abnormal K value were extracted as ROIs (thalamus), and the correlation with the clinical characters and grey matter volume were analysed.

Results: The results revealed that, compared with the HC, the volume transfer constant (K) value of the bilateral thalamus in the schizophrenia group was increased (p < 0.001). There were significant positive correlations between thalamic mean K value with disease duration (p < 0.05) and symptom severity (p < 0.001). Analysis of the thalamic subregions revealed that the BBB disruption was significant in pulvinar, especially the medial pulvinar nucleus (PuM) and lateral pulvinar nucleus (PuL) (p < 0.001). The K value of the whole brain, thalamus, and thalamic subregions was negatively correlated with their volume separately.

Conclusion: These results provided the first in vivo evidence of BBB disruption of thalamus in schizophrenia patients, and the BBB dysfunction might contribute to the pathological brain structural alterations in schizophrenia.
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http://dx.doi.org/10.1016/j.bpsc.2022.06.006DOI Listing
June 2022
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