Publications by authors named "Kun Zhang"

2,304 Publications

  • Page 1 of 1

Potential clinical implications of iron metabolism in ovarian endometriosis.

J Trace Elem Med Biol 2022 Jun 11;73:127017. Epub 2022 Jun 11.

Medical Research Center of Jilin University Second Hospital, Changchun, 130041, China. Electronic address:

Objective: The purpose of this study was to investigate iron metabolism indices in ovarian endometriosis (OEMs) and to demonstrate the potential clinical implications in the initiation and development of OEMs.

Methods: Three datasets in Gene Expression Omnibus (GEO) database were selected to assess the expression levels of iron metabolites in endometrial tissues from patients with EMs and the health. To evaluate the differential expression of serum iron indices , hospitalized patients with OEMs and health examinees in Jilin University Second Hospital from November 2018 to December 2019 were recruited. Serum samples were obtained from 38 patients with OEMs and 36 health examinees. To compare the iron metabolism between peripheral circulation blood and local ectopic lesion, cyst fluid samples were obtained from 15 patients with ovarian chocolate cyst at the time of surgery. Iron metabolism indices include iron, transferrin (TF), ferritin, and unsaturated iron-binding capacity (UIBC)), which were measured by automatic biochemical analyzer.

Results: The present study indicated the increased levels of the iron storage protein, ferritin, in the endometriotic tissues of patients with EMs. The expression of iron and ferritin in cyst fluid of patients with OEMs showed higher than that in serum, the results of TF and UIBC were opposite (P < 0.05). There was no statistical difference in the content of iron metabolites between patients with OEMs and the healthy examinees(P > 0.05).

Conclusion: The ovarian chocolate cyst fluid and endometriotic tissues in patients with OEMs could more directly reflect the pathological changes of local ectopic lesion, which usually manifested as high levels of free iron and/or iron deposits in the ectopic sites. The implications of our work suggest iron metabolites in the serum may have potentially limited value as circulating biomarkers for OEMs. The iron variation in local lesions may be not only regulated by liver that mainly manipulate the systematic iron homeostasis, but also be tuned by the iron regulatory protein (IRP)/ iron responsive element (IRE) system. In summary, the iron metabolites, especially the iron and ferritin in the cyst fluid and endometriotic tissues, are meaningful biomarkers involved in the process of pathophysiology and pathogenesis of OEMs.
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http://dx.doi.org/10.1016/j.jtemb.2022.127017DOI Listing
June 2022

The Association Between Hypertriglyceridemic-Waist Phenotype and Chronic Kidney Disease in Patients with Type 2 Diabetes: A Cross-Sectional METAL Study.

Diabetes Metab Syndr Obes 2022 20;15:1885-1895. Epub 2022 Jun 20.

Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.

Background: The aim of this study was measuring the association between the hypertriglyceridemic-waist (HTGW) phenotype and chronic kidney disease in a large type 2 diabetes population.

Methods: A total of 4254 diabetic patients from the cross-sectional Environmental Pollutant Exposure and Metabolic Diseases in Shanghai (METAL) study were enrolled. The hypertriglyceridemic-waist (HTGW) phenotype was defined as the presence of an elevated waist circumference (WC) and elevated triglyceride (TG) concentration. Chronic kidney disease (CKD) was defined as an estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m or urinary albumin creatinine ratio (uACR) more than 30 mg/g. Linear and multiple logistic regression models were used for measuring the association between HTGW phenotype and chronic kidney disease.

Results: The prevalence of CKD was 29% and 35.8% in total participants and participants with HTGW phenotype, respectively. Subjects in the HTGW phenotype group were more likely to have CKD (OR 1.47, 95% CI: 1.11, 1.95) compared with subjects in the normal waist circumference and normal triglycerides (NTNW) group. HTGW phenotype was both associated with the increasing risk of decreased eGFR (OR 1.31, 95% CI: 1.02, 1.75) and elevated uACR (OR 1.57, 95% CI: 1.18, 2.11). Furthermore, the stratified analysis showed that the strongest positive association between HTGW phenotype and CKD presence was found in the subgroup of presence of hypertension. The associations were all fully adjusted for age, sex, BMI, current smoking, current drinking and other confounding factors.

Conclusion: Our study suggested a positive association between the HTGW phenotype and CKD in Chinese type 2 diabetes patients. Further prospective studies are needed to confirm our findings and to investigate the underlying biological mechanisms.
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http://dx.doi.org/10.2147/DMSO.S359742DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9231417PMC
June 2022

Synthesis of Benzylidene Analogs of Oleanolic Acid as Potential -Glucosidase and -Amylase Inhibitors.

Front Chem 2022 8;10:911232. Epub 2022 Jun 8.

School of Biotechnology and Health Sciences, Wuyi University, Jiangmen, China.

A series of benzylidene analogs of oleanolic acid were synthesized and assessed for their -glucosidase and -amylase inhibitory activities. The results presented that all synthesized analogs exhibited excellent-to-moderate inhibitory effects on -glucosidase and -amylase. Analog showed the highest -glucosidase inhibition (IC: 0.40 μM), and analog presented the strongest -amylase inhibition (IC: 9.59 μM). Inhibition kinetics results showed that analogs and were reversible and mixed-type inhibitors against -glucosidase and -amylase, respectively. Simulation docking results demonstrated the interaction between analogs and two enzymes. Moreover, analogs and showed a high level of safety against 3T3-L1 and HepG2 cells.
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http://dx.doi.org/10.3389/fchem.2022.911232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9213889PMC
June 2022

Novel Gene Rearrangement in the Mitochondrial Genome of Three and Insights Into the Phylogenetic Relationships of .

Front Genet 2022 8;13:922634. Epub 2022 Jun 8.

National Engineering Laboratory of Marine Germplasm Resources Exploration and Utilization, Zhejiang Ocean University, Zhoushan, China.

Complete mitochondrial genomes (mitogenomes) can provide valuable information for phylogenetic relationships, gene rearrangement, and molecular evolution. Here, we report the mitochondrial whole genomes of three species and explore the mechanisms of rearrangements that occur in their mitochondrial genomes. The lengths of the mitogenomes' sequences of , , and were 16,876, 16,861, and 16,835, respectively. They contained 13 protein-coding genes, two ribosomal RNAs, 22 transfer RNA genes, and two identical control regions (CRs). The mitochondrial genomes of three species were rearranged compared to other fish mitochondrial genomes. The , and CR () genes undergo replication followed by random loss of the and genes to form tRNA-Thr, CR1, tRNA-Pro and CR2 (). Tandem duplication and random loss best explain this mitochondrial gene rearrangement. These results provide a foundation for future characterization of the mitochondrial gene arrangement of and further phylogenetic studies.
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http://dx.doi.org/10.3389/fgene.2022.922634DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9213810PMC
June 2022

Piezo1-mediated fluid shear stress promotes OPG and inhibits RANKL via NOTCH3 in MLO-Y4 osteocytes.

Channels (Austin) 2022 Dec;16(1):127-136

Department of Orthopaedics, Gansu Key Laboratory of Orthopaedics, Lanzhou University Second Hospital, Lanzhou, Gansu, China.

Piezo1, a mechanosensitive ion channel, participates in a variety of biological processes in maintaining bone homeostasis. As the most abundant cells in bones of the mammals, osteocytes play an essential role in bone formation, remodeling, and bone mass maintenance. Here, by exposing MLO-Y4 osteocytes to the fluid shear stress (FSS) microenvironment, we explored the effect of Piezo1-mediated FSS on the expression of the molecules critical to the process of bone formation and resorption, Receptor Activator of Nuclear Factor-Kappa-B Ligand (RANKL) and Osteoprotegerin (OPG). It was found that 9 dyne/cm loading for 30 minutes showed an upregulation trend on Piezo1 when MLO-Y4 osteocytes were exposed to an FSS microenvironment. FSS promotes the expression of OPG and inhibits the expression of RANKL. The blocker of Piezo1, GsMTx4, downregulates the effect of FSS on the expression of these two molecules. In addition, NOTCH3 was involved in this process. Thus, the results demonstrated that Piezo1-mediated FSS promotes the expression of OPG and inhibits the expression of RANKL via NOTCH3 in MLO-Y4 osteocytes.
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http://dx.doi.org/10.1080/19336950.2022.2085379DOI Listing
December 2022

Multifunctional Gel Films of Marine Polysaccharides Cross-Linked with Poly-Metal Ions for Wound Healing.

Pharmaceuticals (Basel) 2022 Jun 15;15(6). Epub 2022 Jun 15.

Marine College, Shandong University, Weihai 264209, China.

The development of an efficient and convenient material to improve skin tissue regeneration is a major challenge in healthcare. Inspired by the theory of moist wound healing, portable chitooligosaccharide (COS)/sodium alginate (SA) dual-net gel films containing multiple metal ions were prepared by a casting and in-situ spray method, which can be used to significantly promote wound healing without the use of therapeutic drugs. A variety of divalent cations was introduced in this experiment to improve the advantages of each metal ion by forming metal ion chelates with COS. Moreover, the physicochemical properties and antioxidant properties of nIon-COS/SA gel films were systematically characterized and evaluated by in vitro experiments. The gel films showed good antibacterial activity against Gram-negative and Gram-positive bacteria. In addition, the gel films showed good cytocompatibility in cellular experiments, and the gel films with Zn and Sr addition significantly accelerated wound healing in whole skin defect model experiments. Therefore, this nIon-COS/SA gel film is an ideal candidate material for wound dressing.
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http://dx.doi.org/10.3390/ph15060750DOI Listing
June 2022

Effect of Electroacupuncture Based on ERAS for Preoperative Anxiety in Breast Cancer Surgery: A Single-Center, Randomized, Controlled Trial.

Clin Breast Cancer 2022 Apr 30. Epub 2022 Apr 30.

Department of Acupuncture, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China. Electronic address:

Background: To evaluate the effect of electroacupuncture (EA) based on enhanced recovery after surgery on preoperative anxiety in patients undergoing breast cancer surgery.

Patients And Methods: This was a single-center, randomized, controlled, single-blind clinical trial. Between December 2018 and 2019, 144 female undergoing breast conserving surgery were assigned to conventional (A), preoperative EA (B), intraoperative EA (C), and combination of preoperative and intraoperative EA (D) groups. Primary outcome was the self-rating anxiety scale. Secondary outcomes included visual analogue scale, quality of recovery 40, postoperative complications, and acupuncture-related adverse reactions.

Results: 141 patients completed the trial. Groups B and D self-rating anxiety scale were significantly lower than A and C (P < .01); the sleep quality was significantly better (P < .01). The incidence of nausea at 6 hours postoperatively was significantly lower in group D than other groups (P < .007); the incidence of vomiting at 6 hours postoperatively was better than group A (P < .007). visual analogue scale at 24 hours postoperatively was significantly different between groups A, B, and D (P < .01). Quality of recovery 40 total score at 24 hours postoperatively in group D was significantly higher than A and B (P < .05). The 72-hour postoperative emotional state was most significantly improved in group D (P < .05), while groups B and C showed interactive effect (P < .05).

Conclusion: Preoperative EA alleviated anxiety in the preoperative waiting area, and improved sleep quality. Combination of preoperative and intraoperative EA may be more effective in improving postoperative quality of life.

Trial Registration: Chinese Clinical Trial Registry, ChiCTR1800019979. Registered on December 10, 2018. (http://www.chictr.org.cn/edit.aspx?pid=27653&htm=4).
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http://dx.doi.org/10.1016/j.clbc.2022.04.010DOI Listing
April 2022

miR-92a-1-p5 Modulated Expression of the flightin Gene Regulates Flight Muscle Formation and Wing Extension in the Pea Aphid, Acyrthosiphon pisum (Hemiptera: Aphidoidea).

J Insect Sci 2022 May;22(3)

Henan Key Laboratory of Insect Biology in Funiu Mountain, Henan International Joint Laboratory of Insect Biology, College of Life Science and Agricultural Engineering, Nanyang Normal University, 1638 Wolong Road, Nanyang, Henan 473061, China.

Aphids exhibit wing polyphenism. Winged and wingless aphid morphs are produced by parthenogenesis depending on population density and host plant quality. Recent studies showed that microRNAs in alate and apterous individuals have differential expression and are involved in wing dimorphism of Acyrthosiphon pisum. From which miR-92a-1-p5 can target the mRNA of flight muscle gene flightin in vitro, but what effect they have on wing development of aphid is unclear. Here with the nanocarrier-delivered RNA interference (RNAi) method, flightin gene was knocked down in winged nymphs of A. pisum. Results showed that the majority (63.33%) of adults had malformed wings, the shape of dorsal longitudinal muscle (DLM) was deformed severely, the dorsoventral flight muscle (DVM) became wider and looser in aphids with flightin reduction compared with the negative control. Overexpression of miR-92a-1-p5 caused decreased expression of flightin and malformed wings of aphids, with a mutant ratio of 62.50%. Morphological analysis of flight musculature showed the consistent result as that with flightin knockdown. These results suggest that flightin is essential for flight musculature formation and wing extension in A. pisum, which can be modulated by miR-92a-1-p5.
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http://dx.doi.org/10.1093/jisesa/ieac033DOI Listing
May 2022

Preparation of Ion-COS/SA Multifunctional Gel Films for Skin Wound Healing by an In Situ Spray Method.

Mar Drugs 2022 Jun 18;20(6). Epub 2022 Jun 18.

Marine College, Shandong University, Weihai 264209, China.

The rapid preparation of safe and efficient wound dressings that meet the needs of the entire repair process remains a major challenge for effective therapeutic wound healing. Natural, sprayable Ion-COS/SA multifunctional dual-network gel films created by the in situ coordination of chitooligosaccharide (COS), metal ions and sodium alginate (SA) using casting and an in-situ spray method were synthesized. The gel films exhibited excellent physicochemical properties such as swelling, porosity and plasticity at a COS mass fraction of 3%. Furthermore, at this mass fraction, the addition of bimetallic ions led to the display of multifunctional properties, including significant antioxidant, antibacterial and cytocompatibility properties. In addition, experiments in a total skin defect model showed that this multifunctional gel film accelerates wound healing and promotes skin regeneration. These results suggest that the sprayable Ion-COS/SA multifunctional pro-healing gel film may be a promising candidate for the clinical treatment of allodermic wounds.
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http://dx.doi.org/10.3390/md20060401DOI Listing
June 2022

A Temperature-Sensitive Polymeric Rheology Modifier Used in Water-Based Drilling Fluid for Deepwater Drilling.

Gels 2022 May 30;8(6). Epub 2022 May 30.

Key Laboratory of Unconventional Oil & Gas Development, China University of Petroleum (East China), Ministry of Education, Qingdao 266580, China.

Rheology modifiers are essential for the flat rheology of water-based drilling fluids in deepwater. The low temperature thickening of deepwater water-based drilling fluids results in dramatic rheological changes in the 20-30 °C range. To address such problems, NIPAM with a self-polymerized product LCST of 32-35 °C was selected as the main body for synthesis. While introducing the hydrophilic monomer AM to enhance the thickening properties, the hydrophobic monomer BA was selected to reduce the LCST of the product. In this paper, a temperature-sensitive polymeric rheology modifier (PNBAM) was synthesized by emulsion polymerization using -isopropyl acrylamide, acrylamide, and butyl acrylate as monomers. The PNBAM was characterized using infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), and nuclear magnetic resonance hydrogen spectroscopy (NMR). The rheological properties, temperature resistance, and salt resistance of PNBAM in the base fluid (BF) were tested. The performance of PNBAM in the drilling fluid system was also evaluated, and a water-based drilling fluid system of flat rheology for deepwater was formulated. The rheological modification mechanism of PNBAM was analyzed by turbidity analysis, particle size analysis, and zeta analysis. Experimental results show that PNBAM has good rheological properties. PNBAM is temperature resistant to 150 °C, salt-resistant to 30 wt%, and calcium resistant to 1.0 wt%. PNBAM also has good flat rheology characteristics in drilling fluid systems: AV:AV = 1.27, PV:PV = 1.19. Mechanistic analysis showed that the LCST (Lower Critical Solution Temperature) of 0.2 wt% PNBAM in an aqueous solution was 31 °C. Through changes in hydrogen bonding forces with water, PNBAM can regulate its hydrophilic and hydrophobic properties before and after LCST, which thus assists BF to achieve a flat rheological effect. In summary, the temperature-sensitive effect of PNBAM has the property of enhancing with increasing temperature. While the tackifying effect of conventional rheology modifiers diminishes with increasing temperature, the temperature-sensitive effect of PNBAM gives it an enhanced thickening effect with increasing temperature, making it a more novel rheology modifier compared to conventional treatment additives. After LCST, compared to conventional rheology modifiers (XC), PNBAM has a more pronounced thermo-thickening effect, improving the main rheological parameters of BF by more than 100% or even up to 200% (XC less than 50%). This contributes to the flat rheology of drilling fluids. PNBAM has good application prospects and serves as a good reference for the development of other rheology modifiers.
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http://dx.doi.org/10.3390/gels8060338DOI Listing
May 2022

Exploring the potential mechanism of emetine against coronavirus disease 2019 combined with lung adenocarcinoma: bioinformatics and molecular simulation analyses.

BMC Cancer 2022 Jun 22;22(1):687. Epub 2022 Jun 22.

Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Xi'an Jiaotong University, No. 277 Yanta West Road, Xi'an, 710061, Shaanxi Province, China.

Background: Patients with lung adenocarcinoma (LUAD) may be more predisposed to coronavirus disease 2019 (COVID-19) and have a poorer prognosis. Currently, there is still a lack of effective anti-LUAD/COVID-19 drugs. Thus, this study aimed to screen for an effective anti-LUAD/COVID-19 drug and explore the potential mechanisms.

Methods: Firstly, we performed differentially expressed gene (DEG) analysis on LUAD transcriptome profiling data in The Cancer Genome Atlas (TCGA), where intersections with COVID-19-related genes were screened out. Then, we conducted Cox proportional hazards analyses on these LUAD/COVID-19 DEGs to construct a risk score. Next, LUAD/COVID-19 DEGs were uploaded on Connectivity Map to obtain drugs for anti-LUAD/COVID-19. Finally, we used network pharmacology, molecular docking, and molecular dynamics (MD) simulation to explore the drug's therapeutic targets and potential mechanisms for anti-LUAD/COVID-19.

Results: We identified 230 LUAD/COVID-19 DEGs and constructed a risk score containing 7 genes (BTK, CCL20, FURIN, LDHA, TRPA1, ZIC5, and SDK1) that could classify LUAD patients into two risk groups. Then, we screened emetine as an effective drug for anti-LUAD/COVID-19. Network pharmacology analyses identified 6 potential targets (IL6, DPP4, MIF, PRF1, SERPING1, and SLC6A4) for emetine in anti-LUAD/COVID-19. Molecular docking and MD simulation analyses showed that emetine exhibited excellent binding capacities to DDP4 and the main protease (Mpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Conclusions: This study found that emetine may inhibit the entry and replication of SARS-CoV-2 and enhance tumor immunity by bounding to DDP4 and Mpro.
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http://dx.doi.org/10.1186/s12885-022-09763-2DOI Listing
June 2022

A transcriptomic signature for prostate cancer relapse prediction identified from the differentially expressed genes between TP53 mutant and wild-type tumors.

Sci Rep 2022 Jun 22;12(1):10561. Epub 2022 Jun 22.

Bioinformatics Core of Xavier NIH RCMI Center of Cancer Research, Xavier University of Louisiana, New Orleans, LA, 70125, USA.

For prostate cancer (PCa) patients, biochemical recurrence (BCR) is the first sign of disease relapse and the subsequent metastasis. TP53 mutations are relatively prevalent in advanced PCa forms. We aimed to utilize this knowledge to identify robust transcriptomic signatures for BCR prediction in patients with Gleason score ≥ 7 cancers, which cause most PCa deaths. Using the TCGA-PRAD dataset and the novel data-driven stochastic approach proposed in this study, we identified a 25-gene signature from the genes whose expression in tumors was associated with TP53 mutation statuses. The predictive strength of the signature was assessed by AUC and Fisher's exact test p-value according to the output of support vector machine-based cross validation. For the TCGA-PRAD dataset, the AUC and p-value were 0.837 and 5 × 10, respectively. For five external datasets, the AUCs and p-values ranged from 0.632 to 0.794 and 6 × 10 to 5 × 10, respectively. The signature also performed well in predicting relapse-free survival (RFS). The signature-based transcriptomic risk scores (TRS) explained 28.2% of variation in RFS on average. The combination of TRS and clinicopathologic prognostic factors explained 23-72% of variation in RFS, with a median of 54.5%. Our method and findings are useful for developing new prognostic tools in PCa and other cancers.
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http://dx.doi.org/10.1038/s41598-022-14436-yDOI Listing
June 2022

Potential Mechanisms of in Treating Prostate Cancer Based on Network Pharmacology and Molecular Docking.

Drug Dev Ind Pharm 2022 Jun 22:1-36. Epub 2022 Jun 22.

Modern College of Humanities and Science of Shanxi Normal University, Linfen, Shanxi 041004, P.R. China.

Objective The network pharmacology approach and molecular docking were employed to explore the mechanism of (PF) against prostate cancer (PCa). Methods The active compounds and their corresponding putative targets of PF were identified by the Traditional Chinese Medicine Systems Pharmacology (TCMSP), the gene names of the targets were obtained from the UniProt database. The collection of genes associated with PCa were obtained from GeneCards and DisGeNET database. We merged the drug targets and disease targets by online software, Draw Venn Diagram. The resulting gene list was imported into R software (v3.6.3) for GO and KEGG function enrichment analysis. The STRING database was utilized for protein-protein interaction (PPI) network construction. The cytoHubba plugin of Cytoscape was used to identify core genes. Further, molecular docking analysis of the hub targets were carried out using AutoDock Vina software (v1.5.6). Results A total of 6 active components were screened by PF, with 167 corresponding putative targets, 1395 related targets for PCa, and 113 targets for drugs and diseases. The "drug-component-disease-target" network was constructed by Cytoscape software and the target genes mainly involved in the complex treating effects associated with response to oxidative stress, cytokine activity, pathways in cancer, prostate cancer pathway and TNF signaling pathway. Core genes in the PPI network were TNF, JUN, IL6, IL1B, CXCL8, RELA, CCL2, TP53, IL10 and FOS. The molecular docking results reveal the better binding affinity of 6 active components to the core targets. Conclusion The results of this study indicated that PF may be have a certain anti-PCa effect by regulating related target genes, affecting Pathways in cancer, TNF signaling pathway, Hepatitis B signaling pathway.
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http://dx.doi.org/10.1080/03639045.2022.2088785DOI Listing
June 2022

[Clinical characteristics and cost-effectiveness of intramedullary nail and plate for the treatment of open tibial fractures].

Zhongguo Gu Shang 2022 Jun;35(6):512-20

The Second Department of Orthopaedics, Luonan County Hospital, Shangluo 726100, Shaanxi, China.

Objective: To analyze clinical characteristics and cost-effectiveness of different final surgical options for treating patients with open tibial fractures.

Methods: A retrospective analysis was conducted by enrolling 55 surgically treated patients with open tibial fractures from January 2018 to June 2019. All the patients were categorized in intramedullary nailing (IMN) group and locking compression plate(LCP) group according to the final fixation option. There were 35 cases in group IMN including 27 males and 8 females, aged from 25 to 69 years old with an average of (49.0±10.6) years old. Based on Gustilo-Anderson classification, there were 1 case of typeⅠ, 19 cases of typeⅡand 15 cases of type Ⅲ. There were 20 cases in group LCP including 15 males and 5 females, aged from 46 to 72 years old with an average age of (53.4±14.7) years old. Based on Gustilo-Anderson classification, there were 2 cases of typeⅠ, 11 cases of typeⅡand 7 cases of type Ⅲ. Preoperative waiting time, surgical debridement times, intraoperative bleeding loss, blood and albumin transfusion, operation time, bacterial cultures and complications, bone union time, Johner-Wruhs criteria at 1 year after operation and total cost within 1 year after surgery between two groups were compared. The variables recorded between two groups were statistically analyzed and compared respectively, then the factors affecting hospital costs were evaluated by univariate and multiple linear regression analysis respectively, finally the cost-effectiveness analysis was performed.

Results: Total 55 patients were enrolled with an average follow-up time of(16.4±7.1) months ranged from 14 to 27 months postoperatively. There were no significantly statistical differences of the demographic materials between the two groups. The intraoperative bleeding loss were(243.18±118.82) ml and (467.86±490.53) ml respectively in group IMN and LCP, the significantly statistical difference was discovered(<0.05). The surgical duration were(247.50±57.94) min and(350.00±178.77) min respectively in group IMN and LCP, the significantly statistical difference was discovered(<0.05). There were no significantly statistical differences of the average days before operation, surgical debridement times, received blood and albumin transfusion, wound cultures, complications and bone union time between the two groups(>0.05). The univariate analysis of the factors affecting the hospital costs indicated that patients with smoke or alcohol (=0.042), high energy damage (=0.012), patients with comorbidity diseases(=0.045), surgical debridement over 2 times (=0.001), intraoperative bleeding loss over 400 ml (<0.001), blood and albumin transfusion (=0.027), wound cultures (=0.000) and complications (=0.035) were the factors. The multiple linear regression analysis demonstrated the smoke or alcohol using[=-0.256, =-2.628, 95%CI(-29 667.09, -4 997.47), =0.014] was the only factor affecting the total cost. The excellent and good rate were 80% and 85% respectively based on the Johner-Wruhs criteria. The average total cost within 1 year after surgery was (136 435.90±39 093.98) CNY in group IMN and (140 034.62±56 821.12) CNY in group LCP. The total surgical duration and total intraoperative bleeding loss were significant lower in group IMN than in group LCP. The average total costs of was significantly higher. The average cost for every 1% of excellent and good rate was 1 705.45 CNY in group IMN and 1 647.46 CNY in group LCP. Each 1% increasing of excellent and good rate cost 719.74 CNY more in group LCP compared with group IMN.

Conclusion: Both IMN and LCP could provide a satisfactory outcome for open tibial fractures. Meanwhile considering the total cost, patients with smoke or alcohol history, traffic accident, comorbidity diseases, surgical debridement over 2 times, intraoperative bleeding loss over 400 ml, and complications should not be ignored.
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http://dx.doi.org/10.12200/j.issn.1003-0034.2022.06.003DOI Listing
June 2022

CAU-Net: A Deep Learning Method for Deep Gray Matter Nuclei Segmentation.

Front Neurosci 2022 2;16:918623. Epub 2022 Jun 2.

Department of Radiology, Tianjin Institute of Imaging Medicine, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, China.

The abnormal iron deposition of the deep gray matter nuclei is related to many neurological diseases. With the quantitative susceptibility mapping (QSM) technique, it is possible to quantitatively measure the brain iron content . To assess the magnetic susceptibility of the deep gray matter nuclei in the QSM, it is mandatory to segment the nuclei of interest first, and many automatic methods have been proposed in the literature. This study proposed a contrast attention U-Net for nuclei segmentation and evaluated its performance on two datasets acquired using different sequences with different parameters from different MRI devices. Experimental results revealed that our proposed method was superior on both datasets over other commonly adopted network structures. The impacts of training and inference strategies were also discussed, which showed that adopting test time augmentation during the inference stage can impose an obvious improvement. At the training stage, our results indicated that sufficient data augmentation, deep supervision, and nonuniform patch sampling contributed significantly to improving the segmentation accuracy, which indicated that appropriate choices of training and inference strategies were at least as important as designing more advanced network structures.
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http://dx.doi.org/10.3389/fnins.2022.918623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9204516PMC
June 2022

Effects of Needling on Motor Function for Patients With Parkinson's Disease: Study Protocol for a Multicenter, Randomized Controlled Trial.

Front Neurol 2022 2;13:902170. Epub 2022 Jun 2.

South China Research Center for Acupuncture and Moxibustion, Medical College of Acu-Moxi and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, China.

Background: Although significant progress has been made in the pharmacologic management of Parkinson's Disease (PD), effective management of movement disorders is still a hurdle for therapeutics targeting PD. Acupuncture is one therapeutic option that could potentially improve the motor function of PD and is widely used as adjuvant therapy. Among the various acupuncture approaches, (QHN) therapy has been found to improve motor-function control for patients with PD. However, evidence regarding its efficacy remains scarce. Therefore, to address this need, this study will determine the effects of QHN therapy on motor function in patients with PD and compare it to placebo effects.

Methods: This trial is a multicenter, prospective randomized controlled clinical trial. We randomly allocated 144 participants to two groups of 72 patients. Patients in the treatment group were treated with QHN therapy. The control group had undergone insertion of acupuncture needles at sham acupoints not corresponded to acupuncture points. Participants in the verum treatment group and sham-acupuncture control group received 9 sessions over 6 weeks followed by 8 weeks of follow-up. The primary outcome was the change of motor function from baseline to weeks 6 and 14 measured by the PD Rating Scale-Part III Motor Examination (UPDRS-III). Secondary outcome measures included the change of PD daily quality of life-39 (PDQ-39) and Non-Motor Symptoms Scale for PD (NMSS) from baseline to weeks 6 and 14.

Discussion: The results of this trial will generate data to improve our general understanding of the efficacy of QHN therapy on motor function in patients with PD and thoroughly compare these responses to the placebo effect.

Trial Registration: The trial was registered at the Chinese Clinical Trials Registry (ChiCTR- 2000030871) on 16 March 2020.
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http://dx.doi.org/10.3389/fneur.2022.902170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9201048PMC
June 2022

Activation of GIPR Exerts Analgesic and Anxiolytic-Like Effects in the Anterior Cingulate Cortex of Mice.

Front Endocrinol (Lausanne) 2022 30;13:887238. Epub 2022 May 30.

Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, China.

Background: Chronic pain is defined as pain that persists typically for a period of over six months. Chronic pain is often accompanied by an anxiety disorder, and these two tend to exacerbate each other. This can make the treatment of these conditions more difficult. Glucose-dependent insulinotropic polypeptide (GIP) is a member of the incretin hormone family and plays a critical role in glucose metabolism. Previous research has demonstrated the multiple roles of GIP in both physiological and pathological processes. In the central nervous system (CNS), studies of GIP are mainly focused on neurodegenerative diseases; hence, little is known about the functions of GIP in chronic pain and pain-related anxiety disorders.

Methods: The chronic inflammatory pain model was established by hind paw injection with complete Freund's adjuvant (CFA) in C57BL/6 mice. GIP receptor (GIPR) agonist (D-Ala-GIP) and antagonist (Pro-GIP) were given by intraperitoneal injection or anterior cingulate cortex (ACC) local microinjection. Von Frey filaments and radiant heat were employed to assess the mechanical and thermal hypersensitivity. Anxiety-like behaviors were detected by open field and elevated plus maze tests. The underlying mechanisms in the peripheral nervous system and CNS were explored by GIPR shRNA knockdown in the ACC, enzyme-linked immunosorbent assay, western blot analysis, whole-cell patch-clamp recording, immunofluorescence staining and quantitative real-time PCR.

Results: In the present study, we found that hind paw injection with CFA induced pain sensitization and anxiety-like behaviors in mice. The expression of GIPR in the ACC was significantly higher in CFA-injected mice. D-Ala-GIP administration by intraperitoneal or ACC local microinjection produced analgesic and anxiolytic effects; these were blocked by Pro-GIP and GIPR shRNA knockdown in the ACC. Activation of GIPR inhibited neuroinflammation and activation of microglia, reversed the upregulation of NMDA and AMPA receptors, and suppressed the enhancement of excitatory neurotransmission in the ACC of model mice.

Conclusions: GIPR activation was found to produce analgesic and anxiolytic effects, which were partially due to attenuation of neuroinflammation and inhibition of excitatory transmission in the ACC. GIPR may be a suitable target for treatment of chronic inflammatory pain and pain-related anxiety.
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http://dx.doi.org/10.3389/fendo.2022.887238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9196593PMC
June 2022

Optical Sensing Strategies for Probing Single-Cell Secretion.

ACS Sens 2022 Jun 16. Epub 2022 Jun 16.

Department of Chemistry, Shanghai Stomatological Hospital, State Key Laboratory of Molecular Engineering of Polymers, Fudan University, Shanghai 200433, China.

Measuring cell secretion events is crucial to understand the fundamental cell biology that underlies cell-cell communication, migration, proliferation, and differentiation. Although strategies targeting cell populations have provided significant information about live cell secretion, they yield ensemble profiles that obscure intrinsic cell-to-cell variations. Innovation in single-cell analysis has made breakthroughs allowing accurate sensing of a wide variety of secretions and their release dynamics with high spatiotemporal resolution. This perspective focuses on the power of single-cell protocols to revolutionize cell-secretion analysis by allowing real-time and real-space measurements on single live cell resolution. We begin by discussing recent progress on single-cell bioanalytical techniques, specifically optical sensing strategies such as fluorescence-, surface plasmon resonance-, and surface-enhanced Raman scattering-based strategies, capable of in situ real-time monitoring of single-cell released ions, metabolites, proteins, and vesicles. Single-cell sensing platforms which allow for high-throughput high-resolution analysis with enough accuracy are highlighted. Furthermore, we discuss remaining challenges that should be addressed to get a more comprehensive understanding of secretion biology. Finally, future opportunities and potential breakthroughs in secretome analysis that will arise as a result of further development of single-cell sensing approaches are discussed.
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http://dx.doi.org/10.1021/acssensors.2c00474DOI Listing
June 2022

The rate of thermodynamic cost against adiabatic and nonadiabatic fluctuations of a single gene circuit in Drosophila embryos.

J Chem Phys 2022 Jun;156(22):225101

Department of Chemistry and of Physics and Astronomy, Stony Brook University, Stony Brook, New York 11794-3400, USA.

We study the stochastic dynamics of the externally regulating gene circuit as an example of an eve-skipped gene stripe in the development of Drosophila. Three gene regulation regimes are considered: an adiabatic phase when the switching rate of the gene from the OFF to ON state is faster than the rate of mRNA degradation; a nonadiabatic phase when the switching rate from the OFF to ON state is slower than that of the mRNA degradation; and a bursting phase when the gene switching is fast and transcription is very fast, while the ON state probability is very low. We found that the rate of thermodynamic cost quantified by the entropy production rate can suppress the fluctuations of the gene circuit. A higher (lower) rate of thermodynamic cost leads to reduced (increased) fluctuations in the number of gene products in the adiabatic (nonadiabatic) regime. We also found that higher thermodynamic cost is often required to sustain the emergence of more gene states and, therefore, more heterogeneity coming from genetic mutations or epigenetics. We also study the stability of the gene state using the mean first passage time from one state to another. We found the monotonic decrease in time, i.e., in the stability of the state, in the transition from the nonadiabatic to adiabatic regimes. Therefore, as the higher rate of thermodynamic cost suppresses the fluctuations, higher stability requires higher thermodynamics cost to maintain.
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http://dx.doi.org/10.1063/5.0091710DOI Listing
June 2022

Evaluating the effectiveness of stepwise swallowing training on dysphagia in patients with Alzheimer's disease: study protocol for a randomized controlled trial.

Trials 2022 Jun 13;23(1):490. Epub 2022 Jun 13.

Geriatric Psychiatry Department, Affiliated Brain Hospital of Guangzhou Medical University, 36 MingXin Road, Liwan Distrist, Guangzhou, China.

Background: The high prevalence of dysphagia among Alzheimer's disease (AD) patients has become a public health and economic concern. Therefore, effective and accessible dysphagia treatments are needed. As a fundamental rehabilitation of dysphagia, swallowing muscle exercises have received increased attention. Stepwise swallowing training (SST), integrated with all swallowing organs movement, is expected to improve swallowing dysfunction among AD patients. By using a randomized controlled trial design, we propose a multi-center research to evaluate the effectiveness of SST program among AD patients.

Methods: A multi-center exploratory randomized controlled trial, with a 4-week follow-up period, will be conducted in three major public psychiatric hospitals in Guangdong, China. Participants in the control group will be assigned to routine dysphagia care, while participants in the intervention group will undergo the same nursing care and additionally receive the SST program. The SST program includes five sections of swallowing organs training: lip movement, facial movement, tongue movement, mandibular movement, and neck movement. Primary outcomes evaluate the swallowing function, namely, Water Swallowing Test (WTS) and Standard Swallowing Assessment (SSA). Secondary outcomes aim at measuring the improvement of negative impacts of dysphagia, namely eating behavior, ability of daily activity, and nutritional status. Data will be collected at baseline (T), at 2 weeks (T, intervention), and 4 weeks after intervention (T, follow-up).

Discussion: This study will offer trial-based evidence of the effectiveness of SST in relieving dysphagia among AD patients. SST program is expected to improve both the swallowing function and reduce the negative impacts of dysphagia, with an exploration of acceptability in the SST program.

Trial Registration: Chinese Clinical Trial Registry, ChiCTR2200056481 . Prospectively registered on 6 February 2022.
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http://dx.doi.org/10.1186/s13063-022-06446-yDOI Listing
June 2022

Author Correction: Salidroside promotes peripheral nerve regeneration based on tissue engineering strategy using Schwann cells and PLGA: in vitro and in vivo.

Sci Rep 2022 Jun 13;12(1):9755. Epub 2022 Jun 13.

Guangxi Engineering Center in Biomedical Material for Tissue and Organ Regeneration, Guangxi Medical University, Nanning, China.

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http://dx.doi.org/10.1038/s41598-022-14289-5DOI Listing
June 2022

Erratum: Estrogen receptor α/prolactin receptor bilateral crosstalk promotes bromocriptine resistance in prolactinomas: Erratum.

Int J Med Sci 2022 3;19(5):831-832. Epub 2022 May 3.

Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China.

[This corrects the article DOI: 10.7150/ijms.51176.].
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http://dx.doi.org/10.7150/ijms.71659DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9149644PMC
May 2022

Extract of Jasminum grandiflorum L. alleviates CCl-induced liver injury by decreasing inflammation, oxidative stress and hepatic CYP2E1 expression in mice.

Biomed Pharmacother 2022 Aug 8;152:113255. Epub 2022 Jun 8.

Tea Research Institute, Guangdong Academy of Agricultural Sciences / Guangdong Key Laboratory of Tea Resources Innovation & Utilization, Guangzhou 510640, China. Electronic address:

Jasminum grandiflorum L. (JG) is a medicinal plant containing many bioactive ingredients. Herein, we analyzed the effects of four different extracts and two compounds of JG on acute liver injury caused by carbon tetrachloride (CCl) and underlying molecular mechanisms. 7 weeks old C57BL/6 male mice were used to establish a liver injury model by injecting with 1% CCl, 10 mL/kg ip. Four different extracts and two compounds of JG were given to mice by gavage for 3 days. Clinical and histological chemistry assays were performed to assess liver injury. Moreover, hepatic oxidative stress and inflammation related markers were determined by immunohistochemistry and western blotting. As a result, JG extracts and two functional components showed different degree of protect effects against CCl-induced liver injury by the decrease of elevated serum transaminases and liver index, and the attenuation of histopathological changes in mice, among which JG extracted with petroleum ether (PET) had the most significant effect. In addition, PET remarkably alleviated hepatic oxidative stress and inflammation. Further studies revealed that PET significantly inhibited the TNF-α expression, signal pathway expression, NF-κB p65 and inflammatory factors IL-1β and IL-6 expression in CCl-induced liver injury mice. Nevertheless, hydroxytyrosol (HT) alleviated liver injury by reducing oxidative stress. Apart from PET extract, other extracts of JG can inhibit cytochrome CYP2E1 expression to protect liver tissue. These findings suggest that the extracts and its components of JG possesses the potential protective effects against CCl-induced liver injury in mice by exerting antioxidative stress and anti-inflammation.
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http://dx.doi.org/10.1016/j.biopha.2022.113255DOI Listing
August 2022

Transfer-Learning-Based Gaussian Mixture Model for Distributed Clustering.

IEEE Trans Cybern 2022 Jun 10;PP. Epub 2022 Jun 10.

Distributed clustering based on the Gaussian mixture model (GMM) has exhibited excellent clustering capabilities in peer-to-peer (P2P) networks. However, more iterative numbers and communication overhead are required to achieve the consensus in existing distributed GMM clustering algorithms. In addition, the truth that it cannot find a closed form for the update of parameters in GMM causes the imprecise clustering accuracy. To solve these issues, by utilizing the transfer learning technique, a general transfer distributed GMM clustering framework is exploited to promote the clustering performance and accelerate the clustering convergence. In this work, each node is treated as both the source domain and the target domain, and these nodes can learn from each other to complete the clustering task in distributed P2P networks. Based on this framework, the transfer distributed expectation-maximization algorithm with the fixed learning rate is first presented for data clustering. Then, an improved version is designed to obtain the stable clustering accuracy, in which an adaptive transfer learning strategy is adopted to adjust the learning rate automatically instead of a fixed value. To demonstrate the extensibility of the proposed framework, a representative GMM clustering method, the entropy-type classification maximum-likelihood algorithm, is further extended to the transfer distributed counterpart. Experimental results verify the effectiveness of the presented algorithms in contrast with the existing GMM clustering approaches.
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http://dx.doi.org/10.1109/TCYB.2022.3177242DOI Listing
June 2022

[Distribution Characteristics of Microplastics and Their Migration Patterns in Xiangxi River Basin].

Huan Jing Ke Xue 2022 Jun;43(6):3077-3087

Hubei Field Observation and Scientific Research Stations for Water Ecosystem in Three Gorges Reservoir, Yichang 443002, China.

Microplastics as a prevalent pollutant in water bodies have recently attracted widespread attention. To investigate the spatial and temporal distribution characteristics of microplastics in freshwater rivers and their migration patterns, the surface water, sediments, and subsidence zone of the Xiangxi River, a tributary of the Yangtze River, were sampled and analyzed in November 2020 and April 2021, respectively. The results showed that the average abundance of microplastics in the surface water of Xiangxi River was (6.64±1.32) n·L in flat water and (5.00±1.07) n·L in dry water, the average abundance of microplastics in sediments was (0.56±0.13) n·g in flat water and (0.41±0.09) n·g in dry water, and the average abundance of microplastics in the subsidence zone was (0.53±0.15) n·g in flat water and (0.68±0.18) n·gin dry water. There were significant differences in the abundance distribution of microplastics in the surface water, sediments, and subsidence zone (<0.05). In the surface water and sediments, the particle size of microplastics was mainly distributed in the range of 0.1-0.5 mm, and in the subsidence zone, it mainly ranged from 1-5 mm. The color of microplastics was mainly transparent in the surface water and subsidence zone and blue in sediments. The morphology of microplastics in the Xiangxi River basin was mainly fiber, and the materials were mainly polyethylene (PE) and polypropylene (PP). There were many factors affecting the distribution of microplastics. The analysis results showed that the abundance of microplastics in the surface water was negatively correlated with the flow rate of the water body. The abundance of microplastics in the sediment was related to the substrate type of the riverbed and negatively correlated with the substrate particle size. Combined with the microplastic abundance data of each sampling site, it was found that there was a significant migration process of microplastics in the spatial distribution of the Xiangxi River in the watershed. Along the river longitudinal direction, the longitudinal migration of microplastics in the surface water was along the river direction, and in the vertical direction, it showed the mutual migration between the water body and the subsidence zone and the water body and sediments.
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http://dx.doi.org/10.13227/j.hjkx.202109268DOI Listing
June 2022

Hypoglycemic and Antioxidant Properties of Extracts and Fractions from Polygoni Avicularis Herba.

Molecules 2022 May 24;27(11). Epub 2022 May 24.

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

Our research focused on the hypoglycemic capability and the possible mechanisms of extract and fractions from Polygoni Avicularis Herba (PAH) based on -glucosidase, -amylase inhibition assays, glucose uptake experiment, HPLC-MS analysis, and molecular docking experiment. In addition, DPPH, ABTS, and FRAP assays were used for determining the antioxidant capability. The results of total flavonoids and phenolics contents showed that ethyl acetate fraction (EAF) possessed the highest flavonoids and phenolics with values of 159.7 ± 2.5 mg rutin equivalents/g and 107.6 ± 2.0 mg galic acid equivalents/g, respectively. The results of in vitro hypoglycemic activity showed that all samples had effective -glucosidase inhibition capacities, and EAF possessed the best inhibitory effect with IC value of 1.58 ± 0.24 μg/mL. In addition, n-butanol fraction (NBF) significantly promoted the glucose uptake rate of 3T3-L1 adipocytes. HPLC-MS analysis and molecular docking results proved the interactions between candidates and -glucosidase. The results of antioxidation capacities showed that EAF possessed the best antioxidation abilities with DPPH, ABTS, and FRAP. In summary, the hypoglycemic activity of PAH might be related to the inhibition of -glucosidase (EAF > PEF > NBF) and the promotion of glucose uptake in 3T3-L1 adipocytes (NBF). Simultaneously, the antioxidation capacity of PAH might be related to the abundant contents of flavonoids and other phenolics (EAF > PEF > NBF).
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http://dx.doi.org/10.3390/molecules27113381DOI Listing
May 2022

Malaria oocysts require circumsporozoite protein to evade mosquito immunity.

Nat Commun 2022 Jun 9;13(1):3208. Epub 2022 Jun 9.

Department of Pathogenic Biology, Army Medical University (Third Military Medical University), Chongqing, 400038, China.

Malaria parasites are less vulnerable to mosquito immune responses once ookinetes transform into oocysts, facilitating parasite development in the mosquito. However, the underlying mechanisms of oocyst resistance to mosquito defenses remain unclear. Here, we show that circumsporozoite protein (CSP) is required for rodent malaria oocysts to avoid mosquito defenses. Mosquito infection with CSP parasites (mutation in the CSP pexel I/II domains) induces nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 5 (NOX5)-mediated hemocyte nitration, thus activating Toll pathway and melanization of mature oocysts, upregulating hemocyte TEP1 expression, and causing defects in the release of sporozoites from oocysts. The pre-infection of mosquitoes with the CSP parasites reduces the burden of infection when re-challenged with CSP parasites by inducing hemocyte nitration. Thus, we demonstrate why oocysts are invisible to mosquito immunity and reveal an unknown role of CSP in the immune evasion of oocysts, indicating it as a potential target to block malaria transmission.
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http://dx.doi.org/10.1038/s41467-022-30988-zDOI Listing
June 2022

A reference tissue atlas for the human kidney.

Sci Adv 2022 06 8;8(23):eabn4965. Epub 2022 Jun 8.

University of California San Francisco School of Medicine, San Francisco, CA, USA.

Kidney Precision Medicine Project (KPMP) is building a spatially specified human kidney tissue atlas in health and disease with single-cell resolution. Here, we describe the construction of an integrated reference map of cells, pathways, and genes using unaffected regions of nephrectomy tissues and undiseased human biopsies from 56 adult subjects. We use single-cell/nucleus transcriptomics, subsegmental laser microdissection transcriptomics and proteomics, near-single-cell proteomics, 3D and CODEX imaging, and spatial metabolomics to hierarchically identify genes, pathways, and cells. Integrated data from these different technologies coherently identify cell types/subtypes within different nephron segments and the interstitium. These profiles describe cell-level functional organization of the kidney following its physiological functions and link cell subtypes to genes, proteins, metabolites, and pathways. They further show that messenger RNA levels along the nephron are congruent with the subsegmental physiological activity. This reference atlas provides a framework for the classification of kidney disease when multiple molecular mechanisms underlie convergent clinical phenotypes.
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http://dx.doi.org/10.1126/sciadv.abn4965DOI Listing
June 2022

Trends in Concurrent Opioid and Benzodiazepine Prescriptions in the United States, 2016 to 2019.

Ann Intern Med 2022 Jun 7. Epub 2022 Jun 7.

Clinical Addiction Research and Education Unit, Section of General Internal Medicine, Department of Medicine, Boston University School of Medicine, Boston Medical Center, Boston, Massachusetts.

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http://dx.doi.org/10.7326/M21-4656DOI Listing
June 2022
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