Publications by authors named "Ke Wang"

2,546 Publications

  • Page 1 of 1

Epidermal growth factor receptor mutation p.A864V in small cell lung cancer and lung squamous cell carcinoma: a case report and review of literature.

Anticancer Drugs 2022 Aug 9. Epub 2022 Aug 9.

Department ofPathology The First Affiliated Hospital of Guangxi Medical University, Nanning, China.

Mutations in the epidermal growth factor receptor (EGFR) have been identified in 10-20% of nonsmall cell lung cancer (NSCLC), specifically lung adenocarcinomas. However, these mutations have rarely been reported in small cell lung cancer (SCLC) and lung squamous cell carcinoma (LUSC). Treatment for SCLC and LUSC patients has not yet been established. We present a rare case of p.A864V mutation in Exon 21 of EGFR gene in a patient with both SCLC and LUSC, which is the first case of such mutation type in lung cancer in the world. The patient was a 55-year-old female nonsmoker with stage IV SCLC and LUSC, gene sequencing revealed EGFR gene mutation, she refused EGFR tyrosine kinase inhibitors (TKIs) targeted therapy and received conservative treatment, which led to disease progression. In conclusion, clinicians should be aware of the possibility of the rare EGFR mutations. Platinum-based chemotherapy can be treated for SCLC and LUSC patients.
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http://dx.doi.org/10.1097/CAD.0000000000001324DOI Listing
August 2022

Adrenal heterogeneity in the arterial phase of contrast-enhanced CT predicts prognosis in septic shock: comparison with hollow adrenal gland sign.

Jpn J Radiol 2022 Aug 9. Epub 2022 Aug 9.

Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, No. 58 Zhongshanerlu Road, Guangzhou, Guangdong, People's Republic of China.

Purpose: To evaluate the prognostic value of adrenal heterogeneity in the arterial phase in patients with septic shock, comparatively to the hollow adrenal gland sign (HAGS).

Methods: Totally 84 consecutive patients with septic shock (group S) were assessed retrospectively, and abdominal dual-phase contrast-enhanced CT was performed after the diagnosis of septic shock within one week. The patients were divided into two groups according to clinical outcome, including the survivor (group A, 41 cases) and death (group B, 43 cases) groups. Fifty negative cases were matched as the control (group C). The incidence of the HAGS in patients with septic shock (group S) was statistically analyzed. The average values of left adrenal density (Den-A and Den-V) and their standard deviations (SD-A and SD-V) in dual phases were measured. The above parameters were compared between groups A and B as well as with group C. The parameters were assessed for their predictive values of mortality in septic shock, comparatively to the HAGS.

Results: Compared with group C, group S presented significantly higher Den-A (P = 0.003) and SD-A (P < 0.001). There were significantly higher SD-A (P < 0.001) in group B compared with group A. The incidence of the HAGS was about 27.4% (23/84) in group S. The sensitivity and specificity in predicting poor prognosis in patients with septic shock were 78% and 85% with SD-A, at a cut-off value of 28.64, respectively. The sensitivity and specificity were 41% and 88% for the HAGS, respectively. The area under ROC curve (AUC) was significantly greater for SD-A compared with the HAGS (0.820 vs. 0.670, P < 0.001).

Conclusion: Adrenal heterogeneity in the arterial phase can predict prognosis in patients with septic shock; the larger the SD-A, the poorer the prognosis. The predictive efficiency of adrenal heterogeneity in the arterial phase is better than the HAGS.
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http://dx.doi.org/10.1007/s11604-022-01324-8DOI Listing
August 2022

Subgaleal Effusion and Brain Midline Shift After Cranioplasty: A Retrospective Study Between Polyetheretherketone Cranioplasty and Titanium Cranioplasty After Decompressive Craniectomy.

Front Surg 2022 21;9:923987. Epub 2022 Jul 21.

School of Clinical Medicine, Nanjing Medical University, Nanjing, China.

Cranioplasty with polyetheretherketone (PEEK) has recently shown better cerebral protection performance, improved brain function, and aesthetic contour compared with titanium mesh. However, whether patients undergoing PEEK cranioplasty tend to develop subgaleal effusions remains elusive. This retrospective study included patients who underwent cranioplasty with PEEK implants or titanium mesh after decompressive craniectomy between July 2017 and July 2020. Patient information, including general information, location, size of the defect, subgaleal depth, and brain midline shift was collected and statistically analyzed. There were 130 cases of cranioplasty, including 35 with PEEK implants and 95 with a titanium mesh. Patients who underwent cranioplasty with a PEEK implant had a higher subgaleal effusion rate than those who underwent cranioplasty with titanium mesh (85.71% vs. 53.68%,  < 0.001), while a midline shift >5 mm was more frequently observed in the PEEK group than in the titanium group (20% vs. 6.3%,  = 0.021). The PEEK material was the only factor associated with subgaleal effusion after cranioplasty (OR 5.589,  = 0.002). Logistic regression analysis further showed that age was a protective factor against midline shift in the PEEK cranioplasty group (OR 0.837,  = 0.029). Patients who underwent cranioplasty with PEEK implants were more likely to develop severe subgaleal effusion and significant brain midline shifts than those with titanium mesh implants.
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http://dx.doi.org/10.3389/fsurg.2022.923987DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9351718PMC
July 2022

Apigenin-Mn(II) loaded hyaluronic acid nanoparticles for ulcerative colitis therapy in mice.

Front Chem 2022 22;10:969962. Epub 2022 Jul 22.

Department of Pharmacy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Ulcerative colitis (UC) is a chronic idiopathic inflammatory bowel disease characterized by rapid progression and frequent comorbidities that make its treatment challenging. Nanomaterial-based strategies have been extensively studied to target the GI mucosal immune system in recent years. Herein, we propose a novel apigenin-Mn(II) loaded sodium hyaluronate nanoparticles where apigenin (API) was incorporated in the Mn ramework, coated with hyaluronic acid. The apigenin-Mn(II) loaded sodium hyaluronate nanoparticles (API-Mn(II)@HA NPs) exhibited a diameter of 200 nm and were effective against UC. The preparation of the API-Mn(II) complex was relatively simple, and the mechanism underlying its therapeutic effect on UC induced by sodium dextran sulfate (DSS) was studied in detail. We found that API-Mn(II)@HA nanoparticles could effectively repair the intestinal barrier and significantly improve the damaged colon tissue by mediating inflammatory factors. This study provides novel insights on a new kind of active targeted nanoparticle for improving the efficacy of drugs for UC treatment.
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http://dx.doi.org/10.3389/fchem.2022.969962DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9354835PMC
July 2022

Changes in vesicular glutamate transporter 2 (Vglut2) and vesicular GABA transporter 1 (Vgat1) in the orofacial pain and temperature perception pathway under low estrogen conditions.

Neuro Endocrinol Lett 2022 Jun 7;43(2):88-98. Epub 2022 Jun 7.

Shanxi Medical University School and Hospital of Stomatology,Taiyuan, China.

Objective: To investigate the effects of estrogen on the threshold and temperature of orofacial pain and explore the influence on the function of glutamate and GABA neurons in the orofacial pain temperature perception pathway by observing the expression of vesicular glutamate transporter 2 (Vglut2) and vesicular GABA transporter 1 (Vgat1).

Methods: A total of 24 adult female Sprague-Dawley rats were divided into three groups: sham operation (SHAM), ovariectomized (OVX) and ovariectomized plus estrogen intervention (OVX+E) (n = 8 per group). The threshold of mechanical pain of the orofacial region was assessed with von Frey filaments, and the temperature of the rat orofacial region was monitored by infrared thermography. Changes in the expression of Vglut2 and Vgat1 in glutamatergic and GABAergic neurons in the trigeminal ganglion (TG), spinal trigeminal nucleus (Sp5C), lateral parabrachial nucleus (LPB) and ventral posteromedial nucleus of the thalamus (VPM) were assessed by immunostaining and Western blotting.

Results: Under low-estrogen conditions, the mechanical pain threshold of the orofacial region of rats decreased significantly, and the temperature of the orofacial region increased significantly. The expression of Vglut2 and Vgat1 in the TG and Sp5C showed a downward trend, and the decline in Vgat1 was greater than that in Vglut2. Conversely, both proteins were upregulated in the LPB and VPM, and the magnitude of the changes in Vglut2 was greater than that in Vgat1. Estrogen therapy reversed these changes.

Conclusion: Under low-estrogen conditions, the proportion of glutamate and GABA neurons in the orofacial pain and temperature sensation pathway changes, which leads to the imbalance of neurotransmission function and the enhancement of excitatory transmission of these two kinds of neurons and finally leads to a decrease in the orofacial pain threshold and an increase in temperature.
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June 2022

Cost-effectiveness of lung cancer screening combined with nurse-led smoking cessation intervention: A population-based microsimulation study.

Int J Nurs Stud 2022 Jun 30;134:104319. Epub 2022 Jun 30.

Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China; Shaanxi Provincial Research Center for the Project of Prevention and Treatment of Respiratory Diseases, Xi'an, China; Department of Talent Highland, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China. Electronic address:

Background: The appropriate screening inclusion criteria of low-dose computed tomography screening for lung cancer in Chinese population remains unclear and the effect of combining screening with nurse-led smoking cessation intervention is poorly understood as well.

Objective: We compared the benefits and costs of lung cancer screening with and without nurse-led smoking cessation intervention in different inclusion criteria to help select optimal screening strategies.

Methods: Different screening strategies were set based on diverse starting ages, smoking pack-year and whether nurse-led smoking cessation intervention was applied. We use nationally representative data published by the China Health and Retirement Longitudinal Survey, based on a microsimulation model, to predict incremental cost-effectiveness ratio and net health benefits under different strategies.

Results: The incremental cost-effectiveness ratios for all lung cancer screening strategies were less than three times GDP per capita, and screening combined with smoking cessation intervention had lower incremental cost-effectiveness ratios. The largest net health benefits and probability of cost-effectiveness were both obtained in the strategy which conducted screening and nurse-led smoking cessation intervention for people over 45 years with at least 20 pack-year smoking history. In strategies screening alone, it was obtained in screening for people over 50 years and with at 20 pack-year smoking history.

Conclusions: Nurse-led smoking cessation intervention is recommended provided in conjunction with lung cancer screening. The optimal strategy is conducted screening with cessation intervention for current smokers or smoking quitters in the past 15 years who are over 45 years with at least 20 pack-year smoking history. For strategies screening alone, the target population should be over 50 years old with at least 20 pack year smoking history, when willingness to pay less than three times GPD per capita.
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http://dx.doi.org/10.1016/j.ijnurstu.2022.104319DOI Listing
June 2022

Association of Inhaled Corticosteroids With All-cause Death Risk in COPD Patients: A Meta-analysis of Sixty Randomized Controlled Trials.

Chest 2022 Jul 31. Epub 2022 Jul 31.

Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, China. Electronic address:

Background: Inhaled corticosteroids (ICSs) have been widely used in the maintenance therapy of COPD. However, whether inhaled therapy containing ICSs can reduce the all-cause death risk and the possible benefited patient subgroups are unclear.

Research Question: Does inhaled therapy containing ICSs reduce the all-cause death risk in COPD patients compared with other inhaled therapy not containing ICSs?

Study Design And Methods: We searched PubMed, Cochrane Library, Embase, and Clinical Trials.gov for relevant randomized clinical trials (RCTs). Pooled results were calculated using Peto odds ratios (Peto ORs) with corresponding 95% CIs.

Results: Sixty RCTs enrolling 103,034 patients were analyzed. Inhaled therapy containing ICSs (Peto OR, 0.90; 95% CI, 0.84-0.97), especially triple therapy (Peto OR, 0.73; 95% CI, 0.59-0.91), was associated with a reduction in the cause-death risk among COPD patients when compared to inhaled therapy without ICSs. Subgroup analyses revealed that treatment duration > 6 months (Peto OR, 0.90; 95% CI, 0.83-0.97), medium-dose (Peto OR, 0.71; 95% CI, 0.56-0.91)/low-dose ICSs (Peto OR, 0.88; 95% CI, 0.79-0.97), and budesonide (Peto OR, 0.75; 95% CI, 0.59-0.94) were involved in this association. The predictors of this association included eosinophil counts ≥ 200/μL or percentage ≥ 2%, documented history of moderate and severe exacerbations in the previous year ≥ 2, GOLD stage III or IV, age < 65 years old, and BMI ≥ 25, among which eosinophil counts ≥ 200/μL (Peto OR, 0.58; 95% CI, 0.36-0.95) was the strongest predictor.

Interpretation: Inhaled therapy containing ICSs, especially triple therapy, longer than 6 months, was associated with a reduction in the cause-death risk in COPD patients. The predictors of this association included medication factors and patient characteristics, among which eosinophil counts ≥ 200/μL was the strongest predictor.

Trial Registry: PROSPERO: CRD42022304725; https://www.crd.york.ac.uk/PROSPERO/.
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http://dx.doi.org/10.1016/j.chest.2022.07.015DOI Listing
July 2022

TRPM7 channel inhibition attenuates rheumatoid arthritis articular chondrocyte ferroptosis by suppression of the PKCα-NOX4 axis.

Redox Biol 2022 Jul 19;55:102411. Epub 2022 Jul 19.

Department of Clinical Pharmacology, The Second Hospital of Anhui Medical University, Hefei, 230601, China; The Key Laboratory of Anti-inflammatory and Immune Medicine, Anhui Medical University, Ministry of Education, Hefei, 230032, China. Electronic address:

A role for ferroptosis in articular cartilage destruction associated with rheumatoid arthritis (RA) has not been identified. We previously reported transient receptor potential melastatin 7 (TRPM7) expression was correlated with RA cartilage destruction. Herein, we further characterized a role for TRPM7 in chondrocyte ferroptosis. The expression of TRPM7 was found to be elevated in articular chondrocytes derived from adjuvant arthritis (AA) rats, human RA patients, and cultured chondrocytes treated with the ferroptosis inducer, erastin. TRPM7 knockdown or pharmacological inhibition protected primary rat articular chondrocytes and human chondrocytes (C28/I2 cells) from ferroptosis. Moreover, TRPM7 channel activity was demonstrated to contribute to chondrocyte ferroptosis by elevation of intracellular Ca. Mechanistically, the PKCα-NOX4 axis was found to respond to stimulation with erastin, which resulted in TRPM7-mediated chondrocyte ferroptosis. Meanwhile, PKCα was shown to directly bind to NOX4, which could be reduced by TRPM7 channel inhibition. Adeno-associated virus 9-mediated TRPM7 silencing or TRPM7 blockade with 2-APB alleviated articular cartilage destruction in AA rats and inhibited chondrocyte ferroptosis. Collectively, both genetic and pharmacological inhibitions of TRPM7 attenuated articular cartilage damage and chondrocyte ferroptosis via the PKCα-NOX4 axis, suggesting that TRPM7-mediated chondrocyte ferroptosis is a promising target for the prevention and treatment of RA.
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http://dx.doi.org/10.1016/j.redox.2022.102411DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9344030PMC
July 2022

Correlation of Riolan's arch diameter to treatment choice in patients with isolated superior mesenteric artery dissection.

Abdom Radiol (NY) 2022 Aug 1. Epub 2022 Aug 1.

Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, No. 58 Zhongshanerlu Road, Guangzhou, Guangdong, People's Republic of China.

Objective: To investigate the diameter changes of Riolan's arch in patients with isolated superior mesenteric artery dissection (ISMAD) and to evaluate the implication for treatment selection.

Methods: Ninety-five patients with CT angiography (CTA) confirmed ISMAD were retrospectively included, and another 95 cases with no positive findings on abdominal CTA were included as controls. According to the treatment methods, the patients were subsequently divided into conservative treatment (n = 68) or invasive treatment (n = 27) subgroups. According to the initial CTA images, the prevalence of Riolan's arch as well as its diameter (D) were determined in each subject, and compared between ISMAD and control cases, as well as between patients with different treatments. In patients with ISMAD, dissections were classified according to the Li classification.

Results: Riolan's arch prevalence and D were significantly elevated in the ISMAD group compared with the control group (83.16% vs. 35.79%, P < 0.001; 2.63 ± 0.56 mm vs. 2.12 ± 0.39 mm, P < 0.001). Patients with invasive treatment had significantly higher baseline D (2.93 ± 0.57 mm vs. 1.89 ± 1.14 mm, P < 0.001), and higher proportion of high-risk dissection (P < 0.001) than those administered conservative treatment. Binary logistic regression revealed D (OR = 2.771, 95% CI 1.157-6.638, P = 0.022) and Li classification (OR = 0.107, 95% CI 0.019-0.586, P = 0.010) were independent risk factors for treatment selection. With cutoff of 2.635 mm, the area under the curve, sensitivity, and specificity were 0.805, 0.778 and 0.794, respectively.

Conclusion: Dilation of Riolan's arch is common in patients with ISMAD, and Riolan's arch diameter could be a convenient indicator of disease severity and inform subsequent treatment.
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http://dx.doi.org/10.1007/s00261-022-03622-1DOI Listing
August 2022

Multifunctional nanosystems sequentially regulating intratumor Fenton chemistry by remodeling the tumor microenvironment to reinforce chemodynamic therapy.

Biomater Adv 2022 Jul 27;138:212957. Epub 2022 May 27.

Department of Pharmacy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China. Electronic address:

The particularity of the tumor microenvironment (TME) significantly limits the efficiency of chemodynamic therapy (CDT). Although various measures have been taken to improve the efficiency of CDT, how to organically integrate them into one nanosystem to achieve efficient synergy for CDT according to predetermined procedures is still an urgent problem to be solved. This work reported a multifunctional nanosystem, [email protected], which comprised the inner triphenylphosphine modified D-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS-PPh) micelles loading iron-oxide nanoparticles (IONs), and the outer poly (dopamine-co-protocatechuic acid) (PDA-PA, PP) coating modified with carbonic anhydrase IX inhibitor (CAI). [email protected] remodeled TME by sequential function adjustment to make it suitable for the efficient Fenton reactions: CAI first inhibited the overexpressed CA IX to result in intracellular acidification, which combined with near-infrared light (NIR) irradiation to accelerate the PP coating degradation, thereby promoting the exposure and disintegration of the inner micellar structure to release TPGS-PPh and IONs. The TPGS-PPh further elevated the intracellular ROS basal level by targeting and interfering with the mitochondrial function. Therefore, the TME was transformed into an acidic microenvironment with high ROS levels, which vigorously promoted the Fenton reaction mediated by IONs with the aid of photothermal effect induced by PP coating via NIR irradiation, ultimately earning high-efficiency CDT on xenograft MDA-MB-231 tumor-bearing mice. This study improved the efficiency of Fenton reaction in biological systems through the practical design of nanostructures and provided a novel thought for ROS-mediated therapy.
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http://dx.doi.org/10.1016/j.bioadv.2022.212957DOI Listing
July 2022

Effects of dietary L-leucine supplementation on testicular development and semen quality in boars.

Front Vet Sci 2022 15;9:904653. Epub 2022 Jul 15.

Key Laboratory for Animal Disease-Resistance Nutrition of the Ministry of Agriculture, Animal Nutrition Institute, Sichuan Agricultural University, Yaan, China.

Sperm and seminal plasma are rich in leucine, and leucine can promote the protein synthesis. This property makes it an interesting amino acid to increase sperm quality of human and livestock spermatogenesis. The goal of this study was to explore the effects of dietary leucine supplementation on testicular development and semen quality in boars from weaning to 10 months of age. 30 pure-bred, weaned Duroc boars (8.0 ± 1.0 kg) were randomly divided into two groups: control group (CON; fed the basal diet) and leucine group (LEU; fed the basal diet supplemented with 1.2% leucine); then, their body weight and testicular volume were recorded every 4 weeks. Testes were collected for histological and genes expression analysis from 150-day-old boars. Semen was collected and analyzed. Amino acids contents of blood plasma, seminal plasma, sperm, and testes were determined. Dietary supplementation with leucine increased the testicular volume and weight of boars, compared with CON. Sperm viability, sperm count per ejaculation, and average curve speed of sperm in leucine-supplemented boars were increased. Furthermore, leucine supplementation increased the blood plasma and seminal plasma leucine concentrations, and enhanced the gene expressions of branch chain amino acid transaminase, protein kinase B, mammalian target of rapamycin (), and in the testes. Interestingly, the expressions of the p-mTOR and mTOR proteins in the testes were also upregulated. Thus, dietary leucine supplementation increased leucine absorption and utilization in the testes, promoted testicular development, and improved semen quality of boars, partly through the mTOR signaling pathway.
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http://dx.doi.org/10.3389/fvets.2022.904653DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9334790PMC
July 2022

Sintilimab plus bevacizumab biosimilar IBI305 and chemotherapy for patients with EGFR-mutated non-squamous non-small-cell lung cancer who progressed on EGFR tyrosine-kinase inhibitor therapy (ORIENT-31): first interim results from a randomised, double-blind, multicentre, phase 3 trial.

Lancet Oncol 2022 Jul 28. Epub 2022 Jul 28.

Department of Medical Science and Strategy Oncology, Innovent Biologics, Suzhou, China.

Background: VEGF inhibitors can enhance the efficacy of immunotherapy. However, despite high initial response rates, almost all patients eventually develop treatment resistance to EGFR tyrosine-kinase inhibitors. We aimed to evaluate the efficacy and safety of sintilimab with or without IBI305 plus pemetrexed and cisplatin, compared with pemetrexed and cisplatin alone, for the treatment of patients with locally advanced or metastatic EGFR-mutated non-small-cell lung cancer (NSCLC) who had disease progression after receiving EGFR tyrosine-kinase inhibitor therapy.

Methods: This randomised, double-blind, multicentre, phase 3 trial was conducted at 52 hospitals in China. Eligible participants were adults aged 18-75 years with locally advanced or metastatic NSCLC and EGFR who progressed after receiving a EGFR tyrosine-kinase inhibitor, had an Eastern Cooperative Oncology Group performance status of 0 or 1 with at least one measurable lesion, and an estimated life expectancy of at least 3 months. Participants were randomly assigned (1:1:1) to receive sintilimab (200 mg) plus IBI305 (15 mg/kg) plus pemetrexed (500 mg/m) and cisplatin (75 mg/m), sintilimab plus pemetrexed and cisplatin, or pemetrexed and cisplatin (chemotherapy alone) using block randomisation with stratification according to sex and presence or absence of brain metastases. All study drugs were administered intravenously on day 1 of each cycle, once every 3 weeks. Except for cisplatin, which was only given in the first four cycles, treatment was given for 24 months or until disease progression, intolerable toxic effects, withdrawal of consent, death, or other protocol-specified conditions, whichever occurred first. The primary endpoint was progression-free survival in the intention-to-treat population. We herein report the first planned interim analysis, with progression-free survival results for the comparison between sintilimab plus IBI305 plus chemotherapy versus chemotherapy alone. The progression-free survival results for the sintilimab plus pemetrexed and cisplatin group are immature and not reported here. This study is registered with ClinicalTrials.gov, NCT03802240 (recruiting).

Findings: Between July 11, 2019, and July 31, 2021, 936 patients were screened and 444 were randomly assigned (148 to the sintilimab plus IBI305 plus chemotherapy group, 145 to the sintilimab plus chemotherapy group, and 151 to the chemotherapy alone group). Data cutoff for this interim analysis was July 31, 2021. After a median follow-up of 9·8 months (IQR 4·4-13·3), progression-free survival was significantly longer in the sintilimab plus IBI305 plus chemotherapy group versus the chemotherapy alone group (median 6·9 months [95% CI 6·0-9.3] vs 4·3 months [4·1-5·4]; hazard ratio 0·46 [0·34-0·64]; p<0·0001). The most common grade 3 or 4 treatment-related adverse events were decreased neutrophil count (30 [20%] in the sintilimab plus IBI305 plus chemotherapy group vs 26 [18%] in the sintilimab plus chemotherapy group vs 27 [18%] in the chemotherapy alone group), decreased white blood cell count (17 [11%] vs 12 [8%] vs 13 [9%]), and anaemia (18 [12%] vs ten [7%] vs 15 [10%]). Potentially treatment-related deaths occurred in six patients (intestinal obstruction, gastrointestinal haemorrhage, and myelosuppression in one patient each, and three deaths of unknown cause) in the sintilimab plus IBI305 plus chemotherapy group, and in one patient in the chemotherapy alone group (unknown cause).

Interpretation: In this interim analysis, sintilimab plus IBI305 plus cisplatin and pemetrexed was generally efficacious and well tolerated in patients with EGFR-mutated NSCLC who progressed after receiving EGFR tyrosine-kinase inhibitor therapy.

Funding: Innovent Biologics and the National Natural Science Foundation of China.

Translation: For the Chinese translation of the abstract see Supplementary Materials section.
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http://dx.doi.org/10.1016/S1470-2045(22)00382-5DOI Listing
July 2022

A Nonlinear Constitutive Model for Remoulded Fine-Grained Materials Used under the Qinghai-Tibet Railway Line.

Materials (Basel) 2022 Jul 23;15(15). Epub 2022 Jul 23.

School of Civil Engineering, Harbin Institute of Technology, Harbin 150090, China.

Using undrained triaxial shear tests, this study investigates the mechanical properties of fine-grained materials (silty clay and sand) which are extensively used for China's Qinghai-Tibet Railway (QTR) under different confining pressures () and freezing temperatures (). The results show that a reduction in causes an increase in the shear strength and elastic modulus of all the materials tested in the present study. In addition, the freezing of the silty clay has no significant effect on the type of soil behaviour (strain-hardening), whereas the freezing of the sand changes its strain-hardening behaviour to strain-softening. Supposing that the deviatoric stress-strain curves of the silty clay and sand can be divided into two segments due to a reverse bending point, it was assumed that the first segment follows a hyperbolic function. Meanwhile, the second segment is also a hyperbola, with the reverse bending point as the origin and the residual strength as the asymptote. Accordingly, a nonlinear relation constitutive model that considers and is derived. All model parameters are identified. The reasonability of the new model was verified using the test results of the materials. A comparison of the predicted and test results shows that this model can well simulate the deviatoric stress-strain response in the failure process of the tested materials. In particular, it can reflect the residual deviatoric stress after the materials' failure.
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http://dx.doi.org/10.3390/ma15155119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9330695PMC
July 2022

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

BMC Cancer 2022 Jul 27;22(1):822. Epub 2022 Jul 27.

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

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http://dx.doi.org/10.1186/s12885-022-09836-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9326412PMC
July 2022

AlGaN Quantum Disk Nanorods with Efficient UV-B Emission Grown on Si(111) Using Molecular Beam Epitaxy.

Nanomaterials (Basel) 2022 Jul 21;12(14). Epub 2022 Jul 21.

Key Laboratory of Advanced Photonic and Electronic Materials, School of Electronic Science and Engineering, Nanjing University, Nanjing 210023, China.

AlGaN nanorods have attracted increasing amounts of attention for use in ultraviolet (UV) optoelectronic devices. Here, self-assembled AlGaN nanorods with embedding quantum disks (Qdisks) were grown on Si(111) using plasma-assisted molecular beam epitaxy (PA-MBE). The morphology and quantum construction of the nanorods were investigated and well-oriented and nearly defect-free nanorods were shown to have a high density of about 2 × 10 cm. By controlling the substrate temperature and Al/Ga ratio, the emission wavelengths of the nanorods could be adjusted from 276 nm to 330 nm. By optimizing the structures and growth parameters of the Qdisks, a high internal quantum efficiency (IQE) of the AlGaN Qdisk nanorods of up to 77% was obtained at 305 nm, which also exhibited a shift in the small emission wavelength peak with respect to the increasing temperatures during the PL measurements.
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http://dx.doi.org/10.3390/nano12142508DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9319290PMC
July 2022

Number of Children and Female Labor Participation in China.

Int J Environ Res Public Health 2022 Jul 15;19(14). Epub 2022 Jul 15.

Macquarie Business School, Macquarie University, Sydney, NSW 2109, Australia.

The continuous decrease in the number of women of childbearing age and the consequent decrease in reproductive willingness have contributed to the continuous decrease in labor participation among Chinese women, which has negatively affected the stable socioeconomic development in terms of health. This paper deeply explores the intrinsic relationship between the number of children and women's labor participation based on 2016 data from China Labor-force Dynamic Survey (CLDS). Our results show that there is an "inverted U-shaped" relationship between the number of children and the rate of women's labor involvement; in other words, women's labor participation shows a trend with the increase in the number of children, first rising and then falling; meanwhile, the relationship is more pronounced among women in eastern and central regions and towns. To this end, this study provides a theoretical research basis to effectively alleviate women's selective pressure at home and work, and has a certain reference value for the Chinese government to improve women's employment environment.
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http://dx.doi.org/10.3390/ijerph19148641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9319943PMC
July 2022

Extract Attenuates Light-Induced Photoreceptor Degeneration by Modulating CAV-1-Redoxosome Signaling.

Antioxidants (Basel) 2022 Jun 27;11(7). Epub 2022 Jun 27.

Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia.

The clinical potential of Ginkgo biloba extract (GBE) in the prevention and/or treatment of retinal degenerative diseases has been widely explored; however, the underlying molecular mechanism is poorly understood. Photoreceptor degeneration is the hallmark of retinal degenerative diseases and leads to vision impairment or loss. In this study, the effect of GBE against white light (WL) illumination-induced photoreceptor degeneration was investigated, as well as its underlying mechanism. To evaluate the in vitro activity of GBE, analysis of cell viability, cell apoptosis, oxidative stress, NOX (NADH oxidase) activity and mitochondrial membrane potential (MMP), as well as Western blotting and transcriptome sequencing and analysis, were conducted. To evaluate the in vivo activity of GBE, HE staining, electroretinography (ERG), Terminal-deoxynucleoitidyl transferase (TdT)-mediated nick end labeling (TUNEL) assay and immunofluorescence analysis were conducted. Our study showed that GBE treatment significantly attenuated WL illumination-induced oxidative damage in photoreceptor 661W cells-a finding that was also verified in C57BL/6J mice. Further molecular study revealed that WL illumination downregulated caveolin-1 (CAV-1) expression, interrupted CAV-1-NOX2 interaction, re-located NOX2 from the cell membrane to the cytoplasm and induced the formation of redoxosomes, which led to cell death. However, these cytotoxic events were significantly alleviated by GBE treatment. Interestingly, CAV-1 overexpression showed a consistent protective effect with GBE, while CAV-1 silencing impacted the protective effect of GBE against WL illumination-induced oxidative damage in in vitro and in vivo models. Thus, GBE was identified to prevent photoreceptor cell death due to CAV-1-dependent redoxosome activation, oxidative stress and mitochondrial dysfunction resulting from WL illumination. Overall, our study reveals the protective effect of GBE on photoreceptors against WL illumination-induced oxidative damage in in vitro and in vivo models, which effect is mediated through the modulation of CAV-1-redoxosome signaling. Our findings contribute to better understanding the therapeutic effect of GBE in preventing photoreceptor degeneration in retinal degenerative diseases, and GBE may become a novel therapeutic agent that is effective in reducing the morbidity of these diseases.
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http://dx.doi.org/10.3390/antiox11071268DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9311990PMC
June 2022

Circular RNA-VPS13A attenuates diabetes-induced enteric glia damage by targeting miR-182/GDNF Axis.

Acta Biochim Biophys Sin (Shanghai) 2022 Jun;54(7):1-9

Department of Endocrinology and Metabolism, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.

Gastrointestinal (GI) complications of diabetes mellitus (DM) significantly impact on patients' quality of life. Enteric glial cells (EGC) are the key cell type of enteric nervous system (ENS), which contributes to the destruction of gut homeostasis in DM. Circular RNAs (circRNAs) are a novel type of RNAs abundant in the eukaryotic transcriptome, which form covalently closed continuous loops. In this study, the contribution of circRNAs to EGC damage in DM is investigated. Transcriptome sequencing analysis and functional study show that circVPS13A is significantly down-regulated in hyperglycemia-treated EGC, and circVPS13A overexpression attenuates EGC damage in both in vitro and in vivo DM models. mechanistic study using dual-luciferase reporter assay, affinity-isolation assay, fluorescence in situ hybridization (FISH) and immunostaining analysis identify that circVPS13A exerts its protective effect by sponging miR-182 and then up-regulates glial cell line-derived neurotrophic factor (GDNF) expression. In addition, study confirms that the circVPS13A-miR-182-GDNF network regulation can attenuate hyperglycemia-induced EGC damage of duodenum in streptozotocine (STZ)-induced DM mice. The findings of this study may provide novel insights into the protective role of circVPS13A in DM-associated EGC damage and clues for the development of new therapeutic approaches for the prevention of GI complications of DM.
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http://dx.doi.org/10.3724/abbs.2022073DOI Listing
June 2022

mTOR-FABP4 signal is activated in brain arteriovenous malformations in humans.

J Mol Med (Berl) 2022 Jul 25. Epub 2022 Jul 25.

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Arteriovenous malformations (AVMs) are the most common types of cerebral vascular malformations, which are dynamic lesions with de novo growth potentials. The dysfunction of endothelial cells has been postulated to play a role in the pathogenesis of brain AVMs. mTOR-FABP4 signal enhances the angiogenic responses of endothelial cells and is not activated in the normal cerebral vasculature. Herein, we investigated the hypothesis that the mTOR-FABP4 signal may be activated in brain AVMs. The abundance of molecules in mTOR-FABP4 signal expression was detected by immunohistochemistry and Western blotting; special expressing cells were further characterized by double immunofluorescence using antibodies against various cell-specific markers. Next, several functional assays were performed to analyze the influence of the mTOR-FABP4 signal on proliferation, apoptosis, migration, and vascular tube formation of endothelial cells in human umbilical vein endothelial cells (HUVECs) using rapamycin and L-leucine. The expression of mTOR, p-mTOR, and FABP4 was increased in endothelial cells of human brain AVMs. Endothelial cell mTOR and p-mTOR expression were present in 70% and 55% of brain AVMs, respectively. Moreover, a population of FABP4-positive endothelial cells was detected in 80% of brain AVMs. The mTOR-FABP4 signal was activated and inhibited by L-leucine and rapamycin in HUVECs. The proliferation, apoptosis, migration, and vascular tube formation of endothelial cells could be inhibited by rapamycin. The mTOR-FABP4 signal was activated in human brain AVMs, and the mTOR-FABP4 signal was involved in proliferation, apoptosis, migration, and the vascular tube formation of endothelial cells. Taken together, whether rapamycin has therapeutic potential for treating human brain AVMs is worthy of further study. KEY MESSAGES : We confirmed that the mTOR- FABP4 pathway is activated in human brain arteriovenous malformations. We confirmed that mTOR signaling pathway affects endothelial cell function by regulating proliferation, migration, apoptosis, and tube formation of endothelial cell. Our study can provide theoretical support for mTOR pathway inhibitors in the treatment of human brain arteriovenous malformations.
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http://dx.doi.org/10.1007/s00109-022-02237-9DOI Listing
July 2022

A novel nano material for anti-cerebral ischemia: Preparation and Application of Borneol Angelica Polysaccharide Liposomes.

J Liposome Res 2022 Jul 24:1-13. Epub 2022 Jul 24.

Hunan University of Chinese Medicine, Changsha, China.

Objective: To investigate the preparation of a novel nano liposomes (Borneol Angelica Polysaccharide Liposomes, BAPL) for anti-cerebral ischemia And verify its curative effects and mechanism.

Methods: By applying uniform experiment-design To investigate the fitting combination of BAPL. Encapsulation Efficiency Evaluation of BAPL Preparation; Particle Size and Surface Potential Evaluation of BAPL Biological activity; Cerebral ischemia models of rats Evaluation of BAPL curative effects and mechanism.

Results: (1)The fitting combination of lecithin, Cholesterol, AP mass and the borneol mass was 60mg, 60mg, 45mg and 5mg . the highest encapsulation efficiency was 80.4%, the particle size was 179.1 nm, and the surface zeta potential was -17.2 mV. It is conform to the nano material standards. (2)The results of animal experiments show that: In BAPL group, the infarct volume of TTC staining was significantly decreased, and the expression levels of NF-κBp65, TLR-4, IL-8, IL-6, IL-1β in brain tissue were significantly decreased, while the expression levels of ZO-1, ZO-2, IL-10 were significantly increased after cerebral ischemia-reperfusion.

Conclusion: BAPL is a novel nano and effective material for anti-cerebral ischemia.
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http://dx.doi.org/10.1080/08982104.2022.2106240DOI Listing
July 2022

SALIS transcriptionally represses IGFBP3/Caspase-7-mediated apoptosis by associating with STAT5A to promote hepatocellular carcinoma.

Cell Death Dis 2022 Jul 23;13(7):642. Epub 2022 Jul 23.

Department of Occupational Health and Occupational Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, China.

Hepatocellular carcinoma (HCC) is the most common subtype of liver cancer and the second most fatal cancer in the world despite the great therapeutic advances in the past two decades, which reminds us of the gap in fully understanding the oncogenic mechanism of HCC. To explore the key factors contributing to the progression of HCC, we identified a LncRNA, termed SALIS (Suppression of Apoptosis by LINC01186 Interacting with STAT5A), functions in promoting the proliferation, colony formation, migration and invasion while suppressing apoptosis in HCC cells. Mechanistic study indicated SALIS physically associates with transcription factor STAT5A and binds to the promoter regions of IGFBP3 and Caspase-7 to transcriptionally repress their expression and further inhibit apoptosis. Our findings identified SALIS as an oncogene to promote HCC by physically binding with STAT5A to inhibit the expression of pro-apoptotic IGFBP3 and Caspase-7, which suggests novel therapeutic targets for HCC treatments.
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http://dx.doi.org/10.1038/s41419-022-05094-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9308799PMC
July 2022

The effect of sex differences on complications and 90-day outcomes after aneurysmal subarachnoid hemorrhage: a propensity score-matched analysis.

Neurosurg Rev 2022 Jul 23. Epub 2022 Jul 23.

Department of Neurosurgery, Fengtai District, Beijing Tiantan Hospital, Capital Medical University, No. 119 South Fourth Ring West Road, Beijing, 100070, China.

Aneurysmal subarachnoid hemorrhage (aSAH) is the most devastating form of stroke. Up to now, little is known about the effect of sex differences on complications and outcomes. We retrospectively reviewed aSAH patients admitted to our institution between January 2015 and December 2020. The functional outcomes at discharge and 90 days after discharge were assessed using the modified Rankin Scale (mRS). Baseline characteristics, in-hospital complications, and outcomes were compared after 1:1 propensity score matching (PSM). The area under the curve (AUC) in the receiver operating characteristic curve (ROC) analysis was calculated to measure each independent risk factor's prediction ability. A total of 833 patients were included. After PSM, 109 male patients were compared with 109 female patients. Female patients had a higher incidence of anemia (47/109 [43.1%] vs. 30/109 [27.5%], p = 0.016) than male patients, while male patients had a higher incidence of pneumonia (36/109 [33.0%] vs. 19/109 [17.4%], p = 0.008) than female patients. No significant differences were found in the rate of unfavorable outcomes at discharge and 90-day outcomes (40/109 [36.7%] vs. 50/109 [45.9%], p = 0.169; 15/109 [13.8%] vs. 19/107 [17.8%], p = 0.420) between female and male patients. Pneumonia (AUC = 0.749, 95% confidence interval [CI] = 0.623-0.875, p < 0.001) and anemia (AUC = 0.753, 95% CI = 0.632-0.873, p = 0.002) showed good ability to predict 90-day unfavorable outcomes in male and female patients, respectively. Female patients had a higher incidence of anemia but a lower incidence of pneumonia during hospitalization. However, differences in in-hospital complications did not result in differences in outcomes between women and men. Clinical Trial Registration: NCT04785976. 2021/03/05, retrospectively registered.
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http://dx.doi.org/10.1007/s10143-022-01836-xDOI Listing
July 2022

Effect of Baihe Gujin decoction combined with Shengmai powder on the expression of IL-1β and IL-1Ra in peripheral blood CD14+ monocytes from patients with pulmonary tuberculosis.

Cell Mol Biol (Noisy-le-grand) 2022 Feb 28;68(2):60-63. Epub 2022 Feb 28.

.

This experiment was conducted to investigate the effect of taking Baihe Gujin decoction combined with Shengmai powder on IL-1β and IL-1Ra expression in peripheral blood CD14+ monocytes from patients with pulmonary tuberculosis. For this purpose, one hundred adult patients with primary pulmonary tuberculosis were selected for the study. The age of the enrolled cases ranged from 18 to 60 years old, with a controlled male to the female sex ratio of about 1:1. The Chinese medical evidence was considered to be a qi-yin deficiency type of pulmonary consumption. The patients were randomly divided into experimental and control groups, 50 cases each. In addition, 50 cases of healthy people were selected as a healthy control group, totaling 150 cases. In the experimental group, patients were given Baihe gujin decoction and Shengmai powder based on conventional western medicine, 1 dose for 1 day, 150mL/time for 2 times. The control group was treated with conventional Western medicine. 2 mL of fasting elbow venous blood from the subjects was taken in the morning. Peripheral blood mononuclear cells were isolated by density centrifugation. Monocytes were obtained after incubation with 5 μL of CD14+ immune magnetic beads at 4°C. The relative expression of IL1β and IL1R genes were measured using real-time quantitative PCR (RT-PCR), respectively. Results showed that the relative expression of IL1β and IL1R genes was significantly lower in the experimental group after 3 months compared with the control group, and the statistical difference was highly significant (p<0.01). It was concluded that the administration of Baihe gujin decoction and Shengmai powder was closely related to the relative expression of IL1β and IL1R genes in patients' serum, indicating that Baihe gujin decoction and Shengmai powder have an important role in improving the clinical symptoms of pulmonary tuberculosis.
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http://dx.doi.org/10.14715/cmb/2022.68.2.9DOI Listing
February 2022

The degree of substitution of OSA-modified starch affects the retention and release of encapsulated mint flavour.

Carbohydr Polym 2022 Oct 27;294:119781. Epub 2022 Jun 27.

School of Food Science and Technology, Jiangnan University, Wuxi 214122, Jiangsu Province, China; Key Laboratory of Synthetic and Biological Colloids, Ministry of Education, Wuxi 214122, Jiangsu Province, China; Collaborative Innovation Center of Food Safety and Quality Control, Jiangnan University, Wuxi 214122, Jiangsu Province, China. Electronic address:

This study explored the effect of the degree of substitution (DS) of octenyl succinic anhydride (OSA)-modified starch on the retention and release properties of spray-dried mint flavour microcapsules. The results showed that a higher DS (0.0287, 0.0379) led to greater flavour retention (86.68 %, 90.10 %). The flavour release was negatively correlated with DS during simulated oral processing. A mechanism by which DS affects flavour release was proposed. The emulsifying capacity was improved with increasing DS, thus forming an effective interface. The effective interface increased the partition coefficient, thereby reducing the release. During oral processing, a lower friction coefficient and higher microstructural stability and carrier enzymatic resistance jointly promoted interface stabilization. Data obtained using the EPI suite, a gas chromatograph, a mini traction machine, a Mastersizer analyser and confocal scanning laser microscopy validated this mechanism. This study provides a strategy for designing flavour microcapsules with high retention and slow-release properties using OSA-modified starch.
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http://dx.doi.org/10.1016/j.carbpol.2022.119781DOI Listing
October 2022

Unlocking Interfacial Electron Transfer of Ruthenium Phosphides by Homologous Core-Shell Design toward Efficient Hydrogen Evolution and Oxidation.

Adv Mater 2022 Jul 21:e2204624. Epub 2022 Jul 21.

Frontiers Science Center for Flexible Electronics (FSCFE), Shaanxi Institute of Flexible Electronics (SIFE) & Shaanxi Institute of Biomedical Materials and Engineering (SIBME), Northwestern Polytechnical University (NPU), 127 West Youyi Road, Xi'an, 710072, China.

Developing high-efficiency electrocatalysts for the hydrogen evolution and oxidation reactions (HER/HOR) in alkaline electrolytes is of critical importance for realizing renewable hydrogen technologies. Ruthenium phosphides (RuP ) are promising candidates to substitute Pt-based electrodes; however, great challenges still remain in their electronic structure regulation for optimizing intermediate adsorption. Herein, it is reported that a homologous [email protected] core-shell architecture constructed by a phosphatization-controlled phase-transformation strategy enables strong electron coupling for optimal intermediate adsorption by virtue of the emergent interfacial functionality. Density functional theory calculations show that the RuP core and RuP shell present efficient electron transfer, leading to a close to thermoneutral hydrogen adsorption Gibbs free energy of 0.04 eV. Impressively, the resulting material exhibits superior HER/HOR activities in alkaline media, which outperform the benchmark Pt/C and are among the best reported bifunctional hydrogen electrocatalysts. The present work not only provides an efficient and cost-effective bifunctional hydrogen electrocatalyst, but also offers a new synthetic protocol to rationally synthesize homologous core-shell nanostructures for widespread applications.
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http://dx.doi.org/10.1002/adma.202204624DOI Listing
July 2022

The role of microglial/macrophagic salt-inducible kinase 3 on normal and excessive phagocytosis after transient focal cerebral ischemia.

Cell Mol Life Sci 2022 Jul 21;79(8):439. Epub 2022 Jul 21.

State Key Laboratory of Medical Neurobiology, MOE Frontier Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai, 200032, China.

Previous studies suggested that anti-inflammatory microglia/macrophages (Mi/MΦ) play a role in "normal phagocytosis," which promoted the rapid clearance of necrotic substances and apoptotic cells. More recently, a few studies have found that Mi/MΦ also play a role in "pathological phagocytosis" in the form of excessive or reduced phagocytosis, thereby worsening damage induced by CNS diseases. However, the underlying mechanisms and the Mi/MΦ subtypes related to this pathological phagocytosis are still unknown. Salt-inducible kinase 3 (SIK3), a member of the 5' adenosine monophosphate-activated protein kinase (AMPK) family, has been shown to regulate inflammation in several peripheral diseases. Whether SIK3 also regulates the inflammatory response in CNS diseases is currently unknown. Therefore, in this study, we created a transgenic tamoxifen-induced Mi/MΦ-specific SIK3 conditional knockout (SIK3-cKO) mouse to examine SIK3's role in phagocytotic function induced by transient focal cerebral ischemia (tFCI). By single-cell RNA-seq, we found the pro-inflammatory Mi/MΦ phenotype performed an excessive phagocytotic function, but the anti-inflammatory Mi/MΦ phenotype performed a normal phagocytotic function. We found that SIK3-cKO caused Mi/MΦ heterogenization from the transitional phenotype to the anti-inflammatory phenotype after tFCI. This phenotypic shift corresponded with enhanced phagocytosis of both apoptotic and live neurons. Interestingly, SIK3-cKO enhanced normal phagocytosis of myelin debris but attenuating excessive phagocytosis of non-damaged myelin sheath, thereby protecting white matter integrity after tFCI. CD16, a pro-inflammation marker, was decreased significantly by SIK3-cKO and correlated with "excessive phagocytosis." SIK3-cKO promoted long-term recovery of white matter function and neurological function as assessed with electrophysiological compound action potential (CAPs) and behavioral analysis. This study is the first to show a role of SIK3 in Mi/MΦ phagocytosis in CNS diseases, and reveals that promoting Mi/MΦ anti-inflammatory heterogenization inhibits "excessive phagocytosis" of live cells and facilitates "normal phagocytosis" of apoptotic cells. Therefore, inhibition of SIK3 in Mi/MΦ may be a potential therapeutic target in stroke and other CNS diseases with accompanying white matter destruction. In the acute stage of tFCI, Mi/MΦ polarized into different phenotypes. The pro-inflammatory Mi/MΦ phenotype performed an excessive phagocytotic function. In contrast, the anti-inflammatory Mi/MΦ phenotype performed a normal phagocytotic function. After tFCI, SIK3-cKO promoted anti-inflammatory phenotypic heterogenization of Mi/MΦ. SIK3-cKO promoted Mi/MΦ phagocytosis of apoptotic (normal phagocytosis) and living neuronal cell bodies (excessive phagocytosis) in gray matter. Interestingly, SIK3-cKO specifically increased normal phagocytosis of myelin debris concurrent with an attenuation of excessive phagocytosis of myelin sheath in white matter. These changes induced by SIK3-cKO were associated with protection of white matter integrity and long-term neurofunctional recovery after tFCI.
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http://dx.doi.org/10.1007/s00018-022-04465-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9304053PMC
July 2022

Automatic CD30 scoring method for whole slide images of primary cutaneous CD30 lymphoproliferative diseases.

J Clin Pathol 2022 Jul 21. Epub 2022 Jul 21.

Department of Dermatology, The First Hospital of China Medical University, Shenyang, Liaoning, China

Aims: Deep-learning methods for scoring biomarkers are an active research topic. However, the superior performance of many studies relies on large datasets collected from clinical samples. In addition, there are fewer studies on immunohistochemical marker assessment for dermatological diseases. Accordingly, we developed a method for scoring CD30 based on convolutional neural networks for a few primary cutaneous CD30 lymphoproliferative disorders and used this method to evaluate other biomarkers.

Methods: A multipatch spatial attention mechanism and conditional random field algorithm were used to fully fuse tumour tissue characteristics on immunohistochemical slides and alleviate the few sample feature deficits. We trained and tested 28 CD30 immunohistochemical whole slide images (WSIs), evaluated them with a performance index, and compared them with the diagnoses of senior dermatologists. Finally, the model's performance was further demonstrated on the publicly available Yale HER2 cohort.

Results: Compared with the diagnoses by senior dermatologists, this method can better locate the tumour area and reduce the misdiagnosis rate. The prediction of CD3 and Ki-67 validated the model's ability to identify other biomarkers.

Conclusions: In this study, using a few immunohistochemical WSIs, our model can accurately identify CD30, CD3 and Ki-67 markers. In addition, the model could be applied to additional tumour identification tasks to aid pathologists in diagnosis and benefit clinical evaluation.
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http://dx.doi.org/10.1136/jcp-2022-208344DOI Listing
July 2022

Digital quantum simulation of Floquet symmetry-protected topological phases.

Nature 2022 07 20;607(7919):468-473. Epub 2022 Jul 20.

Department of Physics, ZJU-Hangzhou Global Scientific and Technological Innovation Center, Interdisciplinary Center for Quantum Information, and Zhejiang Province Key Laboratory of Quantum Technology and Device, Zhejiang University, Hangzhou, China.

Quantum many-body systems away from equilibrium host a rich variety of exotic phenomena that are forbidden by equilibrium thermodynamics. A prominent example is that of discrete time crystals, in which time-translational symmetry is spontaneously broken in periodically driven systems. Pioneering experiments have observed signatures of time crystalline phases with trapped ions, solid-state spin systems, ultracold atoms and superconducting qubits. Here we report the observation of a distinct type of non-equilibrium state of matter, Floquet symmetry-protected topological phases, which are implemented through digital quantum simulation with an array of programmable superconducting qubits. We observe robust long-lived temporal correlations and subharmonic temporal response for the edge spins over up to 40 driving cycles using a circuit of depth exceeding 240 and acting on 26 qubits. We demonstrate that the subharmonic response is independent of the initial state, and experimentally map out a phase boundary between the Floquet symmetry-protected topological and thermal phases. Our results establish a versatile digital simulation approach to exploring exotic non-equilibrium phases of matter with current noisy intermediate-scale quantum processors.
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http://dx.doi.org/10.1038/s41586-022-04854-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9300455PMC
July 2022

Improving bread wheat yield through modulating an unselected AP2/ERF gene.

Nat Plants 2022 Jul 18. Epub 2022 Jul 18.

State Key Laboratory of Plant Genomics, Institute of Genetics and Developmental Biology, The Innovative Academy of Seed Design, Chinese Academy of Sciences, Beijing, China.

Crop breeding heavily relies on natural genetic variation. However, additional new variations are desired to meet the increasing human demand. Inflorescence architecture determines grain number per spike, a major determinant of bread wheat (Triticum aestivum L.) yield. Here, using Brachypodium distachyon as a wheat proxy, we identified DUO-B1, encoding an APETALA2/ethylene response factor (AP2/ERF) transcription factor, regulating spike inflorescence architecture in bread wheat. Mutations of DUO-B1 lead to mild supernumerary spikelets, increased grain number per spike and, importantly, increased yield under field conditions without affecting other major agronomic traits. DUO-B1 suppresses cell division and promotes the expression of BH/WFZP, whose mutations could lead to branched 'miracle-wheat'. Pan-genome analysis indicated that DUO-B1 has not been utilized in breeding, and holds promise to increase wheat yield further.
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http://dx.doi.org/10.1038/s41477-022-01197-9DOI Listing
July 2022

Point-of-care non-invasive enzyme-cleavable nanosensors for acute transplant rejection detection.

Biosens Bioelectron 2022 Jul 13;215:114568. Epub 2022 Jul 13.

Lab of Functional and Biomedical Nanomaterials, College of Materials Science and Engineering, Qingdao University of Science and Technology (QUST), Qingdao, 266042, PR China. Electronic address:

Accurate and non-invasive monitoring of allograft posttransplant is essential for early detection of acute cellular rejection and determines the long-term survival of the graft. Clinically, tissue biopsy is the most effective approach for diagnosing transplant rejection. Nonetheless, the procedure is invasive and potentially triggers organ failure. This work aims to design and apply GzmB-responsive nanosensors (GBRNs) that can readily size-change in graft tissues. Subsequently, we investigate the activity of serine protease granzyme B by generating a direct colorimetric urinary readout for non-invasive detection of transplant rejection in under 1 h. In preclinical heart graft mice models of transplant rejection, GBRNs were cleaved by GzmB and excreted by the kidneys via accurate nanometre-size glomerular filtration. By exploiting the catalytic activity of ultrasmall gold nanoclusters, GBRNs urinalysis promotes ultrasensitive surveillance of rejection episodes with a receiver operator characteristic curve area under the curve of 0.896 as well as a 95% confidence interval of about 0.7701-1.000. Besides, the catalytic activity of gold nanoclusters in urine can be detected at point-of-care testing to predict the immunity responses in mice with insufficient immunosuppressive therapy. Therefore, this non-invasive, sensitive, and quantitative method is a robust and informative approach for rapid and routine monitoring of transplant allografts without invasive biopsy.
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http://dx.doi.org/10.1016/j.bios.2022.114568DOI Listing
July 2022
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