Publications by authors named "Jiaxing Zhang"

133 Publications

Association Between Blood Pressure and Branched-Chain/Aromatic Amino Acid Excretion Rate in 24-Hour Urine Samples from Elderly Hypertension Patients.

Diabetes Metab Syndr Obes 2021 10;14:3965-3973. Epub 2021 Sep 10.

School of Public Health and Management, Ningxia Medical University, Yinchuan, Ningxia, People's Republic of China.

Background: Recently, the association between lifestyle-related diseases and free amino acids in the blood plasma-especially branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs)-has been highlighted. However, few studies have been carried out on 24-hour urine samples. Therefore, we aimed to explore the relationships between 24-hour urinary BCAAs and AAAs excretion rate and blood pressure (BP) in elderly patients with hypertension.

Methods And Results: Each of the 322 elderly patients with hypertension completed an in-person questionnaire interview, underwent a physical examination, and provided a 24-hour urine specimen. We measured their BCAAs and AAAs excretion rate, and used multiple linear regression analysis with variable selection to construct models describing the relationships between their BCAAs and AAAs excretion rate and BP. After adjusted for age, gender, height, and weight, valine was inversely associated with both systolic blood pressure (SBP) (: -0.232, 95% CI: -0.16, -0.006) and diastolic blood pressure (DBP) (: -0.144, 95% CI: -0.089, -0.005). These findings were invariant even following adjustment for urine volume and drugs history, and Ile was positively associated with DBP (: 0.170, 95% CI: 0.001, 0.066).

Conclusion: The data revealed that the excretion rate of 24-hour urinary BCAAs was closely related to BP in elderly hypertension patients, and these findings will provide new insights into the association between BACC metabolism and BP.
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http://dx.doi.org/10.2147/DMSO.S324153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8439623PMC
September 2021

HIF-1α/JMJD1A signaling regulates inflammation and oxidative stress following hyperglycemia and hypoxia-induced vascular cell injury.

Cell Mol Biol Lett 2021 Sep 3;26(1):40. Epub 2021 Sep 3.

Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, Guangdong, China.

Background: Endothelial cell (EC) injury accelerates the progression of diabetic macrovascular complications. Hypoxia is an important cause of EC injury. Hypoxia-inducible factor-1 alpha (HIF-1α) is an important hypoxia regulatory protein. Our previous studies showed that high-glucose and hypoxic conditions could upregulate HIF-1α expression and enhance EC inflammatory injury, independently of the nuclear factor kappa-B (NF-κB) pathway. However, it is not clear whether HIF-1α plays a role in vascular disease through epigenetic-related mechanisms.

Methods: We conducted gene expression analysis and molecular mechanistic studies in human umbilical vein endothelial cells (HUVECs) induced by hyperglycemia and hypoxia using RNA sequencing (RNA-seq) and small interfering HIF-1α (si-HIF-1α). We determined HIF-1α and Jumonji domain-containing protein 1 A (JMJD1A) expression by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot, analyzed inflammatory protein secretion in the cell supernatant by enzymelinked immunosorbent assay (ELISA), and assessed protein interaction between HIF-1α and JMJD1A by chromatin immunoprecipitation (Ch-IP). We used the Cell Counting Kit8 (CCK-8) assay to analyze cell viability, and assessed oxidative stress indicators by using a detection kit and flow cytometry.

Results: High glucose and hypoxia up-regulated HIF-1α expression, and down-regulated HIF-1α decreased the level of inflammation and oxidative stress in HUVECs. To determine the downstream pathways, we observed histone demethylases genes and related pathway by RNA-sEq. Among these, JMJD1A was the most upregulated gene in histone demethylases. Moreover, we observed that HIF-1α bound to the promoter of JMJD1A, and the ameliorative effects of si-HIF-1α on oxidative stress and inflammatory cytokines in high-glucose and hypoxia-induced HUVECs were reversed by JMJD1A overexpression. Furthermore, knockdown of JMJD1A decreased inflammatory and oxidative stress injury. To determine the JMJD1A-related factors, we conducted gene expression analysis on JMJD1A-knockdown HUVECs. We observed that downregulation of inflammation and the oxidative stress pathway were enriched and FOS and FOSB might be important protective transcription factors.

Conclusions: These findings provide novel evidence that the HIF-1α/JMJD1A signaling pathway is involved in inflammation and oxidative stress in HUVECs induced by high glucose and hypoxia. Also, this pathway might act as a novel regulator of oxidative stress and inflammatory-related events in response to diabetic vascular injury and thus contribute to the pathological progression of diabetes and vascular disease.
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http://dx.doi.org/10.1186/s11658-021-00283-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8414688PMC
September 2021

Rational design of 17β-hydroxysteroid dehydrogenase type3 for improving testosterone production with an engineered Pichia pastoris.

Bioresour Technol 2021 Aug 25;341:125833. Epub 2021 Aug 25.

Chemical Engineering Research Center, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300350, PR China; State Key Laboratory of Chemical Engineering, Tianjin University, Tianjin 300350, PR China.

Testosterone (TS) is a critical androgenic steroid that regulates human metabolism and maintains secondary sexual characteristics. The biotransformation from 4-androstene-3,17-done (4-AD) to TS is limited by the poor catalytic activity of 17β-hydroxysteroid dehydrogenase type 3 (17β-HSD3). Herein, we explored the structural characteristics and catalytic mechanism of 17β-HSD3 and adopted the rational design strategy to improve its catalytic activity. Molecular docking and molecular dynamics simulations revealed the substrate-binding pocket and the binding mode of 4-AD to 17β-HSD3. We located the pivotal residues and regulated their hydrophobicity and polarity. The obtained G186R/Y195W variant formed additional electrostatic interaction and hydrogen bond with 4-AD, increasing the binding affinity between the variant and 4-AD. Therefore, the G186R/Y195W variant produced 3.98 g/L of TS, which increased to 297%. The combination of structural and mechanism resolution drives the implementation of the rational design strategy, which provides guidance for bioproduction of TS catalyzed by 17β-HSD3.
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http://dx.doi.org/10.1016/j.biortech.2021.125833DOI Listing
August 2021

Biochar amendment to advance contaminant removal in anaerobic digestion of organic solid wastes: A review.

Bioresour Technol 2021 Aug 21;341:125827. Epub 2021 Aug 21.

Beijing Key Laboratory of Farmland Soil Pollution Prevention and Remediation, College of Resources and Environmental Sciences, China Agricultural University, Beijing 100193, China. Electronic address:

Anaerobic digestion (AD) has been widely applied to convert organic solid wastes into biogas, a renewable energy, and digestate, a bio-fertilizer, to sustain waste management. Nevertheless, several vexing contaminants in OSWs restrict digestate application in agriculture. Biochar has been evidenced to effectively improve AD by promoting organic biodegradation and alleviating the accumulation of inhibitory substances (e.g. ammonia and volatile fatty acids). Furthermore, biochar could advance contaminant removal in AD given its highly porous, conductive and alkaline features. Thus, this review aims to highlight the role of biochar amendment to advance contaminant removal in AD of OSWs. Key contaminants, such as antibiotics, heavy metals, microplastics, polycyclic aromatic hydrocarbons, furfural and 5-hydroxy methyl furfural (5-HMF) that ubiquitously present in OSWs were demonstrated. The underlying mechanisms of biochar to amend the removal of these contaminants by AD were discussed. Furthermore, future perspectives to the development of biochar-assisted AD for OSWs treatment were provided.
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http://dx.doi.org/10.1016/j.biortech.2021.125827DOI Listing
August 2021

Upregulation of a novel LncRNA AC104958.2 stabilized by PCBP2 promotes proliferation and microvascular invasion in hepatocellular carcinoma.

Exp Cell Res 2021 Oct 18;407(1):112791. Epub 2021 Aug 18.

Department of Oncology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China. Electronic address:

Long non-coding RNAs (lncRNAs) were reported to be involved in tumorigenesis and progression of hepatocellular carcinoma (HCC). Microvascular invasion (MVI) is an independent predictor for early recurrence and overall survival in postoperative patients with HCC. However, the mechanisms how lncRNAs affect HCC and MVI remain elusive. By RNA sequencing (RNA-seq) in a series of 65 HCC samples and 30 paired adjacent non-tumor liver tissue, we identified a novel lncRNA AC104958.2 that was significantly upregulated in HCC tissues and associated with MVI. Overexpression of AC104958.2 obviously elevated cell viability, metastasis, invasion and epithelial-mesenchymal transition (EMT), while knockout of AC104958.2 mediated by CRISPR/Cas9 technique showed the opposite effects. In addition, the interaction between AC104958.2 and Poly (rC) binding protein 2 (PCBP2) was identified by RNA pull down and mass spectrometry (MS), which was further validated by RNA immunoprecipitation (RIP). PCBP2 was also upregulated in HCC and associated with MVI. High expression of both AC104958.2 and PCBP2 was correlated with tumor size, TNM stage and MVI in HCC. Overexpression of PCBP2 greatly increased the cell viability, metastasis, invasion and EMT. Moreover, actinomycin D assay showed that overexpression of PCBP2 enhanced the RNA stability of AC104958.2. In conclusion, our study showed that a novel lncRNA AC104958.2 exerted oncogenic roles in HCC and might be a promising biomarker and therapeutic target.
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http://dx.doi.org/10.1016/j.yexcr.2021.112791DOI Listing
October 2021

Bending for Better: Flexible Organic Single Crystals with Controllable Curvature and Curvature-Related Conductivity for Customized Electronic Devices.

Angew Chem Int Ed Engl 2021 Aug 10. Epub 2021 Aug 10.

State Key Laboratory of Chemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Weijin Road 92, Tianjin, 300072, China.

Electronic microdevices of self-bending coronene crystals are developed to reveal an unexplored link between mechanical deformation and crystal function. First, a facile approach towards length/width/curvature-controllable micro-crystals through bottom-up solution crystallization was proposed for high processability and stability. The bending crystal devices show a significant increase beyond seven orders of magnitude in conductivity than the straight ones, providing the first example of deformation-induced function enhancement in crystal materials. Besides, double effects caused by bending, including the change of π electron level as well as the enhancement of carrier mobility, were determined, respectively by the X-ray photoelectric spectroscopy and X-ray crystallography to coexist, contributing to the conductivity improvement. Our findings will promote future creation of flexible organic crystal systems with deformation-enhanced functional features towards customized smart devices.
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http://dx.doi.org/10.1002/anie.202108441DOI Listing
August 2021

Chemical profiling of Houttuynia cordata Thunb. by UPLC-Q-TOF-MS and analysis of its antioxidant activity in C2C12 cells.

J Pharm Biomed Anal 2021 Sep 16;204:114271. Epub 2021 Jul 16.

School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China; Department of Traditional Chinese Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China. Electronic address:

Houttuynia cordata Thunb. ("Yu-Xing-Cao"), a traditional Chinese medicinal herb, has long been used to treat various diseases. However, detailed information regarding the chemical constituents of H. cordata aqueous extract is lacking, and the molecular basis of its beneficial effects on muscle is unknown. To investigate these points, in this study, we used ultra-performance liquid chromatography coupled with quadrupole-time-of-flight-mass spectrometry (UPLC-Q-TOF-MS) in positive and negative ion modes to profile and identify the major constituents of H. cordata water extract. A total of 63 peaks were identified based on mass and fragmentation characteristics, including 29 organic acids and their glycosides, 17 flavonoids, 7 volatiles, 4 pyrimidine and purine derivatives, 2 alkaloids, 2 amino acids, 1 isovanillin, and 1 coumarin. The total flavonoid and polyphenol contents of the extract were 4.77 and 139.15 mg/mL, respectively, by ultraviolet spectrophotometry. The cytoprotective activity of H. cordata aqueous extract was evaluated using C2C12 cells treated with tumor necrosis factor (TNF)-α to induce oxidative challenge. The TNF-α induced decrease in cell viability was reversed by treatment for 48 h with the extract; moreover, superoxide dismutase activity was increased while reactive oxygen species level was decreased. These results provide molecular-level evidence for the antioxidant effect of H. cordata extract and highlight its therapeutic potential for the treatment of muscle injury or diseases caused by oxidative stress.
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http://dx.doi.org/10.1016/j.jpba.2021.114271DOI Listing
September 2021

Erratum to "α4 contributes to bladder urothelial carcinoma cell invasion and/or metastasis via regulation of E-cadherin and is a predictor of outcome in bladder urothelial carcinoma patients" [Eur J Canc 50 (2014) 840-851].

Eur J Cancer 2021 Sep 21;155:317. Epub 2021 Jul 21.

State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangdong, Guangzhou 510060, China; Department of Pathology, Sun Yat-Sen University Cancer Center, Guangdong, Guangzhou 510060, China. Electronic address:

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http://dx.doi.org/10.1016/j.ejca.2021.06.030DOI Listing
September 2021

Salidroside Prevents Hypoxia-Induced Human Retinal Microvascular Endothelial Cell Damage Via miR-138/ROBO4 Axis.

Invest Ophthalmol Vis Sci 2021 07;62(9):25

Institute of Brain Diseases and Cognition, Medical College of Xiamen University, Xiamen, Fujian, China.

Purpose: Retinopathies are associated with the injury of retinal microvascular endothelial cells. Salidroside (SAL) is a medicinal supplement that has antioxidative and cytoprotective properties. We hypothesized that SAL might have a protective function in retinopathies. This research aims to explore the function and mechanism of SAL in hypoxia-induced retinal microvascular endothelial cell injury.

Methods: Human retinal microvascular endothelial cells (HRMECs) injury was induced by culturing under hypoxic condition. The function of SAL on HRMECs injury was investigated using cell counting kit-8, 5-ethynyl-2'-deoxyuridine (EdU) staining, flow cytometry, Western blotting, and enzyme linked immunosorbent assay. MicroRNA (miR)-138, roundabout 4 (ROBO4), and proteins in the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathways were examined using quantitative reverse transcription polymerase chain reaction or Western blotting. The target correlation was determined by dual-luciferase reporter analysis and RNA immunoprecipitation.

Results: Hypoxia resulted in proliferation inhibition, cycle arrest, apoptosis, inflammatory reaction, and oxidative stress in HRMECs. SAL attenuated hypoxia-induced HRMECs injury via increasing cell proliferation, and mitigating cycle arrest, apoptosis, inflammatory reaction, and oxidative stress. MiR-138 expression was enhanced by hypoxia, and decreased via SAL stimulation. MiR-138 upregulation reversed the influence of SAL on hypoxia-induced HRMECs injury. ROBO4 was targeted via miR-138. ROBO4 overexpression weakened the role of miR-138 in HRMECs injury. The PI3K/AKT/mTOR pathway was inactivated under hypoxic condition, and SAL increased the activation of PI3K/AKT/mTOR pathways by decreasing miR-138.

Conclusions: SAL protected against hypoxia-induced HRMECs injury through regulating miR-138/ROBO4 axis, indicating the protective potential of SAL in retinopathies.
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http://dx.doi.org/10.1167/iovs.62.9.25DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8297420PMC
July 2021

Different Expressions of HIF-1α and Metabolism in Brain and Major Visceral Organs of Acute Hypoxic Mice.

Int J Mol Sci 2021 Jun 23;22(13). Epub 2021 Jun 23.

Institute of Brain Diseases and Cognition, Medical College of Xiamen University, Xiamen 361102, China.

Hypoxia is associated with clinical diseases. Extreme hypoxia leads to multiple organs failure. However, the different effects of hypoxia on brain and visceral organs still need to be clarified, and moreover, characteristics in vulnerable organs suffering from hypoxia remain elusive. In the present study, we first aimed to figure out the hypoxic sensitivity of organs. Adult male mice were exposed to 6% O or 8% O for 6 h. Control mice were raised under normoxic conditions. In vivo and in vitro imaging of anti-HIF-1α-NMs-cy5.5 nanocomposites showed that the expression level of hypoxia-inducible factor (HIF-1α) was the highest in the liver, followed by kidney and brain. HIF-1α was detected in the hepatocytes of liver, distal convoluted tubules of kidney and neurons of cerebral cortex. The liver, kidney and brain showed distinct metabolic profiles but an identical change in glutamate. Compared with kidney and brain, the liver had more characteristic metabolites and more disturbed metabolic pathways related to glutaminolysis and glycolysis. The level of O-phosphocholine, GTP, NAD and aspartate were upregulated in hypoxic mice brain, which displayed significant positive correlations with the locomotor activity in control mice, but not in hypoxic mice with impaired locomotor activities. Taken together, the liver, kidney and brain are the three main organs of the body that are strongly respond to acute hypoxia, and the liver exhibited the highest hypoxic sensitivity. The metabolic disorders appear to underlie the physiological function changes.
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http://dx.doi.org/10.3390/ijms22136705DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268807PMC
June 2021

High-dose vitamin D3 supplementation ameliorates renal fibrosis by vitamin D receptor activation and inhibiting TGF-β1/Smad3 signaling pathway in 5/6 nephrectomized rats.

Eur J Pharmacol 2021 Sep 17;907:174271. Epub 2021 Jun 17.

Department of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, China. Electronic address:

Renal fibrosis is the pathological consequence of progressive chronic kidney disease. Although it has been reported that vitamin D3 exerts antifibrotic effects, the underlying mechanisms remain unclear. This study is aimed at investigating the effects and molecular mechanisms in high-dose vitamin D3 treatment on renal fibrosis. A model of chronic kidney disease was established by 5/6 nephrectomy in rats characterised by high levels of serum creatine, urea nitrogen, and urinary protein. Serum 25-dihydroxyvitamin D3, calcium and parathormone levels were measured to evaluate vitamin D levels. Hematoxylin and eosin, periodic acid Schiff and Mallory's Trichrome staining were used to evaluate histopathological changes in rats. Moreover, the expression of vimentin, collagen I, α-smooth muscle actin and E-cadherin were analyzed at molecular and histopathological levels. Our results showed that exposure to vitamin D3 decreased the levels of serum creatine, urea nitrogen and urine protein and restored the homeostasis of calcium and parathormone. Vitamin D3 also downregulated the expression of vimentin, collagen I and α-smooth muscle actin and attenuated renal fibrosis and epithelial to mesenchymal transition in the kidney. Importantly, vitamin D3 treatment increased the expression of the vitamin D receptor and inhibited Transforming growth factor-β1 (TGF-β1)/Smad3 signaling pathway in rats kidneys with chronic kidney disease. Mechanistically, the upregulation of TGF-β1 and phosphorylation of Smad3 induced by vitamin D3 was reversed by activation of the vitamin D receptor. Our findings indicated that vitamin D3 is a potential antifibrotic drug in chronic kidney disease via the vitmin D receptor and inhibiting TGF-β1/Smad3 signaling pathway.
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http://dx.doi.org/10.1016/j.ejphar.2021.174271DOI Listing
September 2021

Fractal Model for Predicting Elemental Sulfur Saturation in the Presence of Natural Fracture.

ACS Omega 2021 Jun 21;6(22):14394-14398. Epub 2021 May 21.

Petroleum Engineering Department, Colorado School of Mines, Golden, Colorado 80401, United States.

Sour gas reservoirs are an important part of unconventional gas reservoirs, which are widely distributed in the world. However, elemental sulfur deposition, channel plugging, and productivity reduction consequentially occur in the development of high sour gas fields as pressure drops. The accurate prediction of sulfur deposition is a very important work for sour gas reservoirs. In this paper, a fractal model is presented for predicting elemental sulfur saturation in the presence of natural fracture. The model takes into consideration the effects of non-Darcy flow. In addition, the influence parameters such as fractal dimension, fractal index, and non-Darcy flow are studied. The results showed the following: (1) sulfur deposition was overestimated by Hu's model, and this paper model is more accurate for prediction of sulfur deposition; (2) elemental sulfur deposition decreases with the increase of the fractal dimension, while elemental sulfur deposition increases with the decrease of the fractal index; and (3) non-Darcy flow should be considered because it causes a faster rate of sulfur deposition. This research will provide a basis and reference for predicting elemental sulfur saturation in the presence of natural fracture for sour gas reservoirs.
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http://dx.doi.org/10.1021/acsomega.1c01210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190922PMC
June 2021

Perceptions, Expectations, and Experience of Physicians About Pharmacists and Pharmaceutical Care Services in Pakistan: Findings and Implications.

Front Pharmacol 2021 14;12:650137. Epub 2021 May 14.

Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmacy, Xi'an Jiaotong University, Xi'an, China.

Optimal collaboration between pharmacists and other healthcare professionals such as physicians is integral in implementing pharmaceutical care. However, there are concerns regarding the role of pharmacists, especially among low- and middle-income countries. This study explored the perceptions, expectations, and experience of physicians working in various hospital settings of Punjab, Pakistan, about pharmacists and their roles. A self-administered questionnaire consisting of four sections was administered from October to December 2020. Descriptive and inferential statistics such as Kruskal-Wallis and Mann-Whitney tests were used for data analysis using SPSS. Six hundred and seventy-eight physicians participated in this study with a response rate of 77.9%. Most of the physicians reported minimal to no interaction with pharmacists ( = 521, 76.8%). However, more than three-quarters of physicians ( = 660, 97.3%) accepted pharmacists as evidence-based sources of drug information. In addition, many physicians ( = 574, 84.7%) strongly agreed that pharmacists should attend patient care rounds to respond promptly to questions related to patient medication. A limited number of physicians ( = 124, 18.3%) assumed that pharmacists were advising their patients regarding the judicial use of their drugs. Median expectation and experience score had a significant association with age, experience, and education of physicians ( < 0.05). The perception of physicians was positive toward certain roles of pharmacists, coupled with high expectations. However, their experience was low, with most of the activities of pharmacists due to inadequate interprofessional coordination.
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http://dx.doi.org/10.3389/fphar.2021.650137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160509PMC
May 2021

Self-Templated, Enantioselective Assembly of an Amyloid-like Dipeptide into Multifunctional Hierarchical Helical Arrays.

ACS Nano 2021 06 28;15(6):9827-9840. Epub 2021 May 28.

School of Chemical Engineering and Technology, State Key Laboratory of Chemical Engineering, Tianjin University, Tianjin 300072, People's Republic of China.

Chiral self-assembly of peptides has attracted great interest owing to their promising applications in biomedicine, chemistry, and materials science. However, compared with the rich knowledge about their chiral self-assembly at the molecular or nanoscale, the formation of long-range-ordered hierarchical helical arrays (HHAs) from simple peptides remains a formidable challenge. Herein, we report the self-templated assembly of an amyloid-like dipeptide into long-range-ordered HHAs by their spontaneous fibrillization and hierarchical helical assembly within a confined film. The chiral interactions between the peptide and diamines result in geometry frustration and the phase transition of self-assembling peptide films from achiral spherulite structures into chiral HHAs. By changing the chirality and enantioselective interactions, we can control the phase behavior, handedness, and chiroptics of the self-assembled HHAs precisely. Moreover, the redox activity of the HHAs allows the decoration of nanoparticles with high catalytic activity. These results provide insights into the chiral self-assembly of peptides and the fabrication of highly ordered materials with complex architectures and promising applications in chiroptics and catalysis.
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http://dx.doi.org/10.1021/acsnano.1c00746DOI Listing
June 2021

Alizarin and Purpurin from L. Suppress Insulin Fibrillation and Reduce the Amyloid-Induced Cytotoxicity.

ACS Chem Neurosci 2021 06 25;12(12):2182-2193. Epub 2021 May 25.

Tianjin Key Laboratory of Function and Application of Biological Macromolecular Structures, School of Life Sciences, Tianjin University, Tianjin 300072, P. R. China.

Alizarin (1,2-dihydroxyanthraquinone) and purpurin (1,2,4-trihydroxyanthraquinone), natural anthraquinone compounds from L., are reported to have diverse biological effects including antibacterial, antitumor, antioxidation, and so on, but the inhibition activity against amyloid aggregation has been rarely reported. In this study, we used insulin as a model protein to explore the anti-amyloid effects of the two compounds. The results showed that alizarin and purpurin inhibited the formation of insulin fibrils in a dose-dependent manner and reduced insulin-induced cytotoxicity. Meanwhile, purpurin had a more significant inhibitory effect on insulin amyloid fibrils compared with alizarin. In addition, computer simulations indicated that the two compounds interacted mainly with the hydrophobic residues of insulin chain B and interfered with the binding of phenylalanine residues. The research indicated that natural anthraquinone compounds had potential effects in preventing protein misfolding diseases and could be further used to design effective antiamyloidosis compounds.
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http://dx.doi.org/10.1021/acschemneuro.1c00177DOI Listing
June 2021

Self-Assembly of Peptide Hierarchical Helical Arrays with Sequence-Encoded Circularly Polarized Luminescence.

Nano Lett 2021 08 20;21(15):6406-6415. Epub 2021 May 20.

School of Chemical Engineering and Technology, State Key Laboratory of Chemical Engineering, Tianjin University, Tianjin 300072, P.R. China.

Self-assembled peptide materials with sequence-encoded properties have attracted great interest. Despite their intrinsic chirality, the generation of circularly polarized luminescence (CPL) based on the self-assembly of simple peptides has been rarely reported. Here, we report the self-assembly of peptides into hierarchical helical arrays (HHAs) with controlled supramolecular handedness. The HHAs can emit full-color CPL signals after the incorporation of various achiral fluorescent molecules, and the value is 40 times higher than that of the CPL signal from the solutions. By simply changing the amino acid sequence of the peptides, CPL signals with opposite handedness can be generated within the HHAs. The peptide HHAs can provide hydrophobic pockets to accommodate the fluorescent molecules with helical arrangement through strong aromatic stacking interactions, which are responsible for the CPL signals. This work provides a pathway to construct highly ordered chiral materials, which have broad applications in the chiroptical field.
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http://dx.doi.org/10.1021/acs.nanolett.1c00697DOI Listing
August 2021

Occurrence and fate of N-nitrosamines in three full-scale drinking water treatment systems with different treatment trains.

Sci Total Environ 2021 Aug 9;783:146982. Epub 2021 Apr 9.

Institute of Environmental Engineering & Nano-Technology, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, Guangdong, China; Guangdong Provincial Engineering Research Centre for Urban Water Recycling and Environmental Safety, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, Guangdong, China; School of Environment, Tsinghua University, Beijing 100084, China. Electronic address:

The occurrence of mutagenic and carcinogenic N-nitrosamines in drinking water is of great concern. In this study, dynamics and removal of nine N-nitrosamines in three drinking water treatment systems of a southern city of China are monitored during one year of sampling. The impacts of physicochemical treatment units on the removal and generation of N-nitrosamines were evaluated. The O and KMnO based pre-oxidation units have caused an increase in N-nitrosamines concentration, with O showing the substantial generation of N-nitrosamines. The carbon filter and ultrafiltration membrane units were found effective in removing N-nitrosamine precursors. These drinking water treatment systems have been useful in removing N-nitrosamine precursors; meanwhile, a slight decrease was found in already formed N-nitrosamines concentration. However, N-nitrosomorpholine (NMOR) and N-nitrosodiphenylamine (NDPhA) were found resistant toward all kinds of physicochemical treatments, and negligible changes in concentration were noted in all drinking water treatment systems. The distribution networks in the city provided an effective contact period to residual chlorine and precursors, which caused an increase in N-nitrosamines concentration. Overall, N-nitrosodimethylamine (NDMA) and N-nitroso-diethylamine (NDEA) have been found near the cancer risk threshold (10) in all of the drinking water treatment systems, while the remaining seven N-nitrosamines were found below the risk level.
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http://dx.doi.org/10.1016/j.scitotenv.2021.146982DOI Listing
August 2021

The association between body composition and metabolically unhealthy profile of adults with normal weight in Northwest China.

PLoS One 2021 25;16(3):e0248782. Epub 2021 Mar 25.

School of Public Health and Management, Ningxia Medical University, Yinchuan, Ningxia, China.

Objective: Related evidences of metabolically unhealthy profile of adults with normal weight are not well characterized in the Chinese population. This is because they cannot be effectively identified by regular measurements (such as body mass index [BMI]). To overcome this gap in literature, this study aimed at investigating the association between body composition and metabolically unhealthy profile in Chinese adults with normal weight.

Methods: A total of 5427 individuals with normal-weight were recruited from 15820 people living in Ningxia Hui Autonomous Region in Northwest China. Normal-weight was defined as a BMI of 18.5-23.9 kg/m2. Metabolically unhealthy profile was assessed by the National Cholesterol Education Program Adult Treatment Panel III (ATP III). Metabolically unhealthy normal-weight (MUHNW) profile was defined in individuals who had normal weight and at least two cardiometabolic risk factors. Generalized linear model was used to investigate the association between body composition measured by bioelectrical impedance and metabolically unhealthy profile in adults with normal-weight.

Results: The percentage of metabolically unhealthy profile was 35.86% in adults with normal weight. Different MUHNW distributions were found between males and females depending on age. The percentage of the MUHNW profile significantly increased in women after the age of 55, contrary to men. The association between body composition and MUHNW was affected by age and sex. The increased adiposity indices (fat mass index [FMI], visceral fat level [VFL], waist circumference [WCF]), and reduced skeletal muscle mass ratio [SMR] showed significant differences between MUHNW and metabolically healthy with normal weight (MHNW) (p < 0.05).

Conclusion: The distribution of MUHNW differed between ages and sexes. FMI, VFL, WCF and SMR could be responsible for the MUHNW adults, providing a new insight into the potential metabolic risks for the adults with normal weight in China. This directs us in the management of the MUHNW for their early prevention.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248782PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993598PMC
March 2021

A novel cell culture system modeling the SARS-CoV-2 life cycle.

PLoS Pathog 2021 03 12;17(3):e1009439. Epub 2021 Mar 12.

School of Medicine, Tsinghua University, Beijing, China.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the global pandemic of COVID-19. SARS-CoV-2 is classified as a biosafety level-3 (BSL-3) agent, impeding the basic research into its biology and the development of effective antivirals. Here, we developed a biosafety level-2 (BSL-2) cell culture system for production of transcription and replication-competent SARS-CoV-2 virus-like-particles (trVLP). This trVLP expresses a reporter gene (GFP) replacing viral nucleocapsid gene (N), which is required for viral genome packaging and virion assembly (SARS-CoV-2 GFP/ΔN trVLP). The complete viral life cycle can be achieved and exclusively confined in the cells ectopically expressing SARS-CoV or SARS-CoV-2 N proteins, but not MERS-CoV N. Genetic recombination of N supplied in trans into viral genome was not detected, as evidenced by sequence analysis after one-month serial passages in the N-expressing cells. Moreover, intein-mediated protein trans-splicing approach was utilized to split the viral N gene into two independent vectors, and the ligated viral N protein could function in trans to recapitulate entire viral life cycle, further securing the biosafety of this cell culture model. Based on this BSL-2 SARS-CoV-2 cell culture model, we developed a 96-well format high throughput screening for antivirals discovery. We identified salinomycin, tubeimoside I, monensin sodium, lycorine chloride and nigericin sodium as potent antivirals against SARS-CoV-2 infection. Collectively, we developed a convenient and efficient SARS-CoV-2 reverse genetics tool to dissect the virus life cycle under a BSL-2 condition. This powerful tool should accelerate our understanding of SARS-CoV-2 biology and its antiviral development.
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http://dx.doi.org/10.1371/journal.ppat.1009439DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990224PMC
March 2021

Photocatalytic degradation of ranitidine and reduction of nitrosamine dimethylamine formation potential over MXene-TiC/MoS under visible light irradiation.

J Hazard Mater 2021 07 13;413:125424. Epub 2021 Feb 13.

Institute of Environmental Engineering & Nano-Technology, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, Guangdong, China; School of Environment, Tsinghua University, Beijing 100084, China. Electronic address:

Photocatalysis is an effective method to degrade ranitidine (RAN), which is a typical precursor of nitrosamine dimethylamine (NDMA), an extremely potent human carcinogen. Herein, MXene-TiC/MoS composites were prepared by a hydrothermal treatment aiming to use them for the photocatalytic degradation of RAN and the reduction of NDMA formation potential (NDMA-FP) under visible light irradiation for the first time. The analysis of the morphology, chemical composition and structure of these composites as well as the results of electrochemical experiments showed that a heterojunction was formed between MoS and TiC, which facilitated the separation of electron-hole pairs and charge transfer, and thereby the photocatalytic performance. The MXene-TiC/MoS composite (MT-4) exhibited the best photocatalytic performance in 60 min, with the highest RAN degradation and mineralization efficiencies of 88.4% and 73.58%, and the lowest NDMA-FP of 2.01%. Active species, including •O radicals, h and •OH radicals, all contributed to the degradation of RAN, among which •OH radicals were the main active species involved in the photocatalytic activity. The mechanism of the photocatalytic degradation of RAN over MXene-TiC/MoS photocatalyst under visible light irradiation was proposed. This work opens up a new perspective on the applications of MXene-based materials for photocatalytic degradation of challenging pollutants.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125424DOI Listing
July 2021

An effective enzymatic assay for pH selectively measuring direct and total bilirubin concentration by using of CotA.

Biochem Biophys Res Commun 2021 04 19;547:192-197. Epub 2021 Feb 19.

Chemical Engineering Research Center, School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300072, PR China; State Key Laboratory of Chemical Engineering, Tianjin University, Tianjin, 300072, PR China. Electronic address:

In this study, we aimed to develop B. subtilis spore coat protein A (CotA) for the enzymatic determination of bilirubin. Firstly, molecular docking and oxidation kinetic analysis confirmed the feasibility of CotA for oxidizing bilirubin. Secondly, CotA showed pH-preferable oxidization performance to direct bilirubin (DB) in acidic conditions and an alkaline-catalytic oxidation capacity to total bilirubin (TB). Mechanism analysis results confirm that the conformational changes of CotA, DB and UB caused by pH changes are responsible for the selective oxidation of DB and TB by CotA. Then, CotA exhibits better structural characteristics and enzymatic performance than M. verrucaria-derived bilirubin oxidase (Mv-BOD). Besides, the strong anti-interference ability helps CotA adapt to complex catalytic environment in the detection of DB and TB. Our results prove that CotA can be used as a promising candidate bio-enzymatic detection reagent for DB and TB.
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http://dx.doi.org/10.1016/j.bbrc.2021.01.094DOI Listing
April 2021

A site-specific DNA methylation biosensor for both visual and magnetic determination based on lateral flow assay.

Analyst 2021 Apr 18;146(7):2248-2254. Epub 2021 Feb 18.

College of Life Sciences, Northwest University, Xi'an, 710069, China.

Tumorigenesis driven by abnormal DNA methylation has highlighted the need to develop a portable, rapid and sensitive strategy for accurate methylation detection with a specific cancer-prognostic gene, which caters to the popularization of precision medicine. In this study, a site-specific biosensor for both visual and magnetic DNA methylation determination has been established based on lateral flow assay. By introducing digoxin- and biotin-labeled primers into PCR, the amplicons can be recognized and captured by gold magnetic nanoparticles (GMNPs) in this biosensor. Working as a signal probe, the optical property of GMNPs allows the amplicons to be interpreted with naked eyes avoiding any complex equipment and cumbersome operation after PCR. Moreover, by virtue of the magnetic property of GMNP, the signal can be explained and recorded by a magnetometer in clinical practice. The introduction of tailor-made primer sets makes it possible to accurately distinguish 0.1% methylated variants in the presence of numerous unmethylated variants as strong interferential background and vice versa at target cytosine-guanine dinucleotide. A distinct signal can be observed with as low as 0.01 pg variants for both visual and magnetic analyses. As a significant tumor suppressor gene, the promoter methylation status of miR-34a is accurately determined with not only cell lines but also with clinical samples, which demonstrates the great potential of this biosensor for cancer diagnosis and prognosis.
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http://dx.doi.org/10.1039/d0an02277bDOI Listing
April 2021

Protective effects of three structurally similar polyphenolic compounds against oxidative damage and their binding properties to human serum albumin.

Food Chem 2021 Jul 14;349:129118. Epub 2021 Jan 14.

School of Life Sciences, Tianjin University, Tianjin 300072, PR China; Tianjin Key Laboratory of Function and Application of Biological Macromolecular Structures, Tianjin University, Tianjin 300072, PR China. Electronic address:

Brazilin (Bra), hematoxylin (Hto) and hematein (Hte) are structurally similar polyphenols having rich biological activities, but their antioxidant ability has not been well studied. Here, their protective ability against human serum albumin (HSA) oxidative degradation were investigated using 2,2'-Azobis (2-methylpropionamidine) dihydrochloride (AAPH), NaClO and Fenton like reactions methods. The results indicated that polyphenols inhibited the oxidative injuries of HSA in the order: Hto > Bra > Hte. Additionally, the biological effects of polyphenols were mostly influenced by their binding to protein. Therefore, the structure-affinity relationships of polyphenols binding to HSA were also explored. Fluorescence experiments indicated that polyphenols bound to HSA through static quenching mechanism. Furthermore, some conformational changes of HSA could be observed in the presence of polyphenols. Altogether, molecular structure of polyphenols played a significant role in their protective effect against HSA oxidative damage and binding ability, which provided fundamental insights into their application as health care foods.
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http://dx.doi.org/10.1016/j.foodchem.2021.129118DOI Listing
July 2021

Determining the leading sources of N-nitrosamines and dissolved organic matter in four reservoirs in Southern China.

Sci Total Environ 2021 Jun 26;771:145409. Epub 2021 Jan 26.

Institute of Environmental Engineering & Nano-Technology, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, Guangdong, China; Guangdong Provincial Engineering Research Centre for Urban Water Recycling and Environmental Safety, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, Guangdong, China; State Key Joint Laboratory of Environmental Simulation and Pollution Control, School of Environment, Tsinghua University, Beijing 100084, China. Electronic address:

The presence of carcinogenic N-nitrosamines and dissolved organic matter (DOM) in freshwater is a significant concern from the perspective of public health and drinking water treatment plant operation. This study investigated the N-nitrosamines concentration and their precursors' distributions, and DOM composition in four reservoirs located in a southern city of China. A total of 22 renowned precursors were identified. Precursors from industrial and pharmaceutical origins were found to be dominant in all reservoirs; however, traces of pesticide-based precursors, i.e. pirimicarb and cycluron were also found. The distribution of nine N-nitrosamines was substantially different among the reservoirs. N-Nitrosodibutylamine (NDBA), N-Nitrosopiperidine (NPIP), N-Nitrosodimethylamine (NDMA), and N-Nitrosopyrrolidine (NPYR) were abundantly present in all reservoirs. Most of N-nitrosamines except NDMA and N-nitrosodiethylamine (NDEA) were far below the generally accepted cancer risk of 10, and NDMA/NDEA were found close to the risk level (10). Anthropogenic DOM was dominant in three reservoirs as depicted by a higher biological index (BIX) than the humification index (HIX). By the principle component analysis, BIX appeared as an indicator of N-nitrosamines (except NDEA and NPIP). A strong and direct relationship was observed between the NDMA-formation potential (FP) and concentration of total N-nitrosamines (∑NA), and BIX. These results confirmed that the anthropogenic activities were the leading source of DOM and N-nitrosamines in this city based on land-use.
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http://dx.doi.org/10.1016/j.scitotenv.2021.145409DOI Listing
June 2021

A year-long cyclic pattern of dissolved organic matter in the tap water of a metropolitan city revealed by fluorescence spectroscopy.

Sci Total Environ 2021 Jun 19;771:144850. Epub 2021 Jan 19.

Institute of Environmental Engineering & Nano-Technology, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, Guangdong, China; Guangdong Provincial Engineering Research Centre for Urban Water Recycling and Environmental Safety, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen, 518055, Guangdong, China; School of Environment, Tsinghua University, Beijing 100084, China. Electronic address:

Delivering drinking water with stable quality in metropolitan cities is a big challenge. This study investigated the year-long dynamics of dissolved organic matter (DOM) in the tap water and source water of a metropolitan city in southern China using fluorescence spectroscopy. The DOM detected in the tap water, and source water of Shenzhen city was season and location-dependent. A year-long cyclic trend of DOM was found with predominate protein-like fluorescence in the dry season compared to the humic-like enriched DOM in the wet season. A general DOM pattern was estimated by measuring the shift in dominant fluorescence regions on the excitation-emission matrix (EEM). The difference in fluorescent DOM (FDOM) composition (in terms of the ratio of protein-like to humic-like fluorescence) was above 200% between wet and dry seasons. The taps associated with reservoirs receiving water from the eastern tributary of Dongjiang River showed significant changes in protein-like contents than the taps with source water originating from the western part of the river. This study highlights the importance of optimizing drinking water treatment plants' operational conditions after considering seasonal changes and source water characteristics.
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http://dx.doi.org/10.1016/j.scitotenv.2020.144850DOI Listing
June 2021

Circular RNA circSDHC serves as a sponge for miR-127-3p to promote the proliferation and metastasis of renal cell carcinoma via the CDKN3/E2F1 axis.

Mol Cancer 2021 01 20;20(1):19. Epub 2021 Jan 20.

Department of Oncology, The First Affiliated Hospital of Sun Yat-sen University, No. 58, Zhongshan road II, Guangzhou, 510080, People's Republic of China.

Background: There is increasing evidence that circular RNAs (circRNAs) have significant regulatory roles in cancer development and progression; however, the expression patterns and biological functions of circRNAs in renal cell carcinoma (RCC) remain largely elusive.

Method: Bioinformatics methods were applied to screen for circRNAs differentially expressed in RCC. Analysis of online circRNAs microarray datasets and our own patient cohort indicated that circSDHC (hsa_circ_0015004) had a potential oncogenic role in RCC. Subsequently, circSDHC expression was measured in RCC tissues and cell lines by qPCR assay, and the prognostic value of circSDHC evaluated. Further, a series of functional in vitro and in vivo experiments were conducted to assess the effects of circSDHC on RCC proliferation and metastasis. RNA pull-down assay, luciferase reporter and fluorescent in situ hybridization assays were used to confirm the interactions between circSDHC, miR-127-3p and its target genes.

Results: Clinically, high circSDHC expression was correlated with advanced TNM stage and poor survival in patients with RCC. Further, circSDHC promoted tumor cell proliferation and invasion, both in vivo and in vitro. Analysis of the mechanism underlying the effects of circSDHC in RCC demonstrated that it binds competitively to miR-127-3p and prevents its suppression of a downstream gene, CDKN3, and the E2F1 pathway, thereby leading to RCC malignant progression. Furthermore, knockdown of circSDHC caused decreased CDKN3 expression and E2F1 pathway inhibition, which could be rescued by treatment with an miR-127-3p inhibitor.

Conclusion: Our data indicates, for the first time, an essential role for the circSDHC/miR-127-3p/CDKN3/E2F1 axis in RCC progression. Thus, circSDHC has potential to be a new therapeutic target in patients with RCC.
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http://dx.doi.org/10.1186/s12943-021-01314-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816303PMC
January 2021

High expression of neutrophil cytosolic factor 2 (NCF2) is associated with aggressive features and poor prognosis of esophageal squamous cell carcinoma.

Int J Clin Exp Pathol 2020 1;13(12):3033-3043. Epub 2020 Dec 1.

Department of Extracorporeal Circulation, The First Affiliated Hospital, Sun Yat-sen University Guangzhou 510080, China.

Background: In the development of several human cancers, it has been established that neutrophil cytosolic factor 2 (NCF2) plays a major part. Therefore, possible functions of NCF2 in ESCC are investigated in this paper.

Methods: The mRNA/protein expression of NCF-2 in ESCC cell lines and tissues were found based on quantitative real-time reverse transcription PCR (qRT-PCR), western blotting, and immunohistochemistry (IHC). A large cohort consisting of 194 postoperative ESCC samples was used for IHC. These data were analyzed based on Chi-square test, Kaplan-Meier analysis, and Cox regression modelling. For the purpose of confirming its role in ESCC cells, we used short hairpin RNA (ShRNA) interfering method to suppress endogenous NCF2 expression.

Results: NCF2 was significantly up-regulated for in ESCC tissues and cell lines in at mRNA and protein levels; and NCF-2 expression was absent for all normal esophageal epithelium detected by IHC. Furthermore, the knockdown of NCF-2 compromised the proliferation and invasion of ESCC cells in vitro.

Conclusion: Positive NCF2 expression in ESCC may facilitate an aggressive phenotype. This may be an independent biomarker in ESCC.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791380PMC
December 2020

Could the ambient higher temperature decrease the transmissibility of COVID-19 in China?

Environ Res 2021 02 3;193:110576. Epub 2020 Dec 3.

School of Public Health and Management, Ningxia Medical University, Yinchuan, 750001, Ningxia, China; The Key Laboratory of Environmental Factors and Chronic Disease Control of Ningxia, Yinchuan, 750001, Ningxia, China. Electronic address:

Background: Existing literatures demonstrated that meteorological factors could be of importance in affecting the spread patterns of the respiratory infectious diseases. However, how ambient temperature may influence the transmissibility of COVID-19 remains unclear.

Objectives: We explore the association between ambient temperature and transmissibility of COVID-19 in different regions across China.

Methods: The surveillance data on COVID-19 and meteorological factors were collected from 28 provincial level regions in China, and estimated the instantaneous reproductive number (R). The generalized additive model was used to assess the relationship between mean temperature and R.

Results: There were 12,745 COVID-19 cases collected in the study areas. We report the associated effect of temperature on R is likely to be negative but not of statistical significance, which holds for most Chinese regions.

Conclusions: We found little statistical evidence for that the higher temperature may reduce the transmissibility of COVID-19. Since intensive control measures against the COVID-19 epidemics were implemented in China, we acknowledge this may impact the underlying effect size estimation, and thus cautiousness should be taken when interpreting our findings.
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http://dx.doi.org/10.1016/j.envres.2020.110576DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7713592PMC
February 2021

The Effectiveness of Clinical Pharmacist-Led Consultation in the Treatment of Infectious Diseases: A Prospective, Multicenter, Cohort Study.

Front Pharmacol 2020 8;11:575022. Epub 2020 Sep 8.

Department of Pharmacy, Guizhou Provincial People's Hospital, Guiyang, China.

Background: Antimicrobial resistance (AMR) is a serious global health threat and leads to a huge challenge to infectious diseases (ID) treatment. To tackle AMR, regional 'Antimicrobial Stewardship Programs' (ASP) have been implemented in many countries. Due to insufficient clinical pharmacy resources, a major intervention mode of ASP in China is through clinical pharmacist-led consultation (CPC). The current study aims to prospectively evaluate this intervention and compare the effectiveness of CPC served by ID and non-ID clinical pharmacists.

Methods: We conducted a prospective and multicenter cohort study based on a regional registry database in 17 hospitals in Western China, including consecutive patients with ID between April 2017 and December 2019. Baseline characteristics including sex, age, liver and kidney function, comorbidity, infection severity were prospectively collected and recorded. The main exposure of interest was whether the attending physician adopted recommendations of the clinical pharmacist in the therapeutic scheme. The outcome was the infection effective response, assessed during day 3-7 after completing CPC. Multivariate analyses were performed by generalized linear mixed models.

Results: A total of 2,663 ID patients were included in the final analysis according to the predesigned inclusion and exclusion criteria. The number of patients whose treatment followed and did not follow the pharmacists' suggestion was 2,529 and 134, respectively. CPC intervention could improve the ID patient prognosis in the context of other confounders controlled (()=1.838, 95%()=[1.212, 2.786]), and the effectiveness of CPC served by ID and non-ID clinical pharmacists might be equivalent (=0.958, 95%[0.740, 1.240]). Special consultation (=1.832, 95%[1.106, 3.035]) and surgical treatment of infectious sites (=1.380, 95%[1.039, 1.834]) had positive influences on the patient prognosis, while hypoalbuminemia (=0.694, 95%[0.523, 0.921]), liver dysfunction (=0.705, 95%[0.559, 0.889]), presence of high-risk factors (=0.775, 95%[0.613, 0.980]), and increased infection severity (=0.631, 95%[0.529, 0.753])were associated with a decrease in effective response rate, independently.

Conclusion: This study suggests that CPC is a promising pharmacist-led intervention to improve ID treatment, and it can achieve standardization among clinical pharmacists with different backgrounds by some measures. Policy/decision-makers should promote this intervention mode in developing countries or regions where there is an insufficient number of clinical pharmacists.
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http://dx.doi.org/10.3389/fphar.2020.575022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7506045PMC
September 2020

Molecular Architecture of the SARS-CoV-2 Virus.

Cell 2020 10 6;183(3):730-738.e13. Epub 2020 Sep 6.

School of Life Sciences, Tsinghua University, Beijing 100084, China; Beijing Advanced Innovation Center for Structural Biology & Frontier Research Center for Biological Structure, Beijing 100084, China; Tsinghua-Peking Center for Life Sciences, Beijing 100084, China. Electronic address:

SARS-CoV-2 is an enveloped virus responsible for the COVID-19 pandemic. Despite recent advances in the structural elucidation of SARS-CoV-2 proteins, the detailed architecture of the intact virus remains to be unveiled. Here we report the molecular assembly of the authentic SARS-CoV-2 virus using cryoelectron tomography (cryo-ET) and subtomogram averaging (STA). Native structures of the S proteins in pre- and postfusion conformations were determined to average resolutions of 8.7-11 Å. Compositions of the N-linked glycans from the native spikes were analyzed by mass spectrometry, which revealed overall processing states of the native glycans highly similar to that of the recombinant glycoprotein glycans. The native conformation of the ribonucleoproteins (RNPs) and their higher-order assemblies were revealed. Overall, these characterizations revealed the architecture of the SARS-CoV-2 virus in exceptional detail and shed light on how the virus packs its ∼30-kb-long single-segmented RNA in the ∼80-nm-diameter lumen.
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http://dx.doi.org/10.1016/j.cell.2020.09.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7474903PMC
October 2020
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