Publications by authors named "Tao Sun"

1,841 Publications

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High Performance Flip-Structure Enhancement-Mode HEMT with Face-to-Face Double Gates.

Nanoscale Res Lett 2022 Aug 11;17(1):73. Epub 2022 Aug 11.

The State Key Laboratory of Electronic Thin Films and Integrated Devices, University of Electronic Science and Technology of China, Chengdu, 610054, China.

A novel double gates flip-structure enhancement-mode (E-mode) high electron mobility transistor with step field plate (DFF HEMT) is proposed. It features face-to-face double gates, including a top trench MIS gate with a step field plate and a bottom planar MIS gate, which is shorted together. In the on-state, the double gates not only can restore the 2DEG by the higher electric potential, but also can form the electron accumulation layers, and thus increase the saturation output current and reduce the on-resistance. The face-to-face double gates together deplete the 2DEG by using the work function difference to realize E-mode, instead of by etching the AlGaN layer under the gate for the conventional MIS gate E-mode HEMT. The double-gate structure not only avoids etch damage, but also maintains both high threshold voltage and low on-resistance. Meanwhile, the step gate field plate modulates E-field distribution to increase the BV. In order to easily fabricate, the trench gate with step field plate must be located on the top of device, forming the flip-structure. The flip-structure is also beneficial to decrease the leakage current in the substrate. The simulated V, BV and I of the DFF HEMT are 0.8 V, 465 V and 494 mA/mm, respectively. The FOM of the DFF HEMT is 79.8% and 444.2% higher than those of the conventional MIS-FP HEMT and MIS HEMT.
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http://dx.doi.org/10.1186/s11671-022-03713-4DOI Listing
August 2022

Pattern of play behavior in infant (age 1 to 12 months) white-headed langurs in limestone forests, southwest China.

Ecol Evol 2022 Aug 4;12(8):e9160. Epub 2022 Aug 4.

Key Laboratory of Ecology of Rare and Endangered Species and Environmental Protection (Guangxi Normal University), Ministry of Education Guilin Guangxi China.

Play behavior is a significant trait of immature nonhuman primates (hereafter primates) that plays an important role in sensory, locomotor, socio-cognitive, and developmental processes. It has been suggested that the function of play is to practice and improve motor skills related to foraging, avoiding predators, attracting mates, raising offspring, and strengthening the skills needed for the formation and maintenance of social bonds. From September 2009 to August 2010, we investigated the play behavior of 1-12 month-old infant white-headed langurs () a Critically Endangered primate species endemic to China. We carried out this study in the Guangxi Chongzuo White-headed Langur National Nature Reserve, and recorded 4421 play bouts and 1302 min of play engaged in by seven infants. We found that infants of different ages exhibited different patterns of play behavior. Specifically, nonsocial play behaviors appeared at one month of age, social play behaviors at two months, and an expanded repertoire of social and non-social play behaviors at three months of age. The frequency and duration of nonsocial play peaked at five months of age and then decreased, while social play gradually increased with age. Nonsocial play did not differ between the sexes, whereas social play showed sex specificity, with a higher frequency and longer duration of social play in male infants compared to female infants. In addition, male and female white-headed langur infants appeared to prefer individuals of same sex as social playmates, but no obvious choice preference for a specific individual. In conclusion, we provide the first report of play behavior in a population of wild Critically Endangered white-headed langurs. We suggest that age- and sex-specific differences in play behavior of infants form the bases for age and sex-based differences in the social interactions of adult langurs.
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http://dx.doi.org/10.1002/ece3.9160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9351325PMC
August 2022

Construction of gas permeable channel in poly(l-lactic acid) membrane and its control of the micro atmosphere in okra packaging.

Int J Biol Macromol 2022 Aug 5. Epub 2022 Aug 5.

College of Food Science and Engineering, Inner Mongolia Agricultural University, 306 Zhaowuda Road. Hohhot, Inner Mongolia 010018, China. Electronic address:

An atmosphere within a package affects the metabolic process of food and the microbial growth of fresh products and has a vital role in preserving food. It depends on the membrane's specific gas permeability and selectivity to generate a desirable atmosphere for storage. In this study, triblock poly(l-lactic acid‑d-ɛ-caprolactone) (PLDC) copolymers and three-arm poly(l-lactic acid-g-ɛ-caprolactone) (PLGC) star copolymers were synthesized, in which a microphase-separated morphology of sea-island structure was established in PLGC membrane as a gas "fast permeation channel" for regulating CO and O permeability and CO/O selectivity. AFM observation revealed different well-defined micro phase-separated structures of PLGC with size ranges of 200- 300 nm. Comparing PLGC membrane with PLLA, CO and O transmission rates increased by 416.9 % and 132.7 %, while HO transport rates increased by 245.6 %. Mechanical testing shows that the PLGC membrane exhibits 40.8-fold elongation at break compared to PLLA, showing excellent flexibility. Moreover, okra's equilibrium-modified atmosphere packaging was designed based on a theoretically derived model. Preservation results suggested that the PLGC packaging membrane could generate an ideal high 8.7- 9.2 % CO and low 2.3- 2.7 % O atmosphere for okra preservation, delaying the discoloring and rotting of okra.
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http://dx.doi.org/10.1016/j.ijbiomac.2022.08.010DOI Listing
August 2022

Population pharmacokinetics and model-informed precision dosing of lamivudine in Chinese HIV-infected patients with mild and moderate impaired renal function.

Expert Rev Clin Pharmacol 2022 May 6;15(5):647-655. Epub 2022 Jun 6.

Department of Clinical Research Center, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.

Background: Lamivudine is a first-line medication used for human immunodeficiency virus (HIV) treatment. To date, the population pharmacokinetics of lamivudine in Chinese HIV-infected adults have not been assessed. This study aimed to develop a population pharmacokinetic model for oral lamivudine in Chinese HIV-infected adults and to determine the optimal lamivudine dosage regimens.

Research Design And Methods: A total of 1113 samples, from 828 Chinese HIV-infected patients treated with lamivudine 300 mg every 24 hours, were pooled from two open-label, prospective clinical trials. A population pharmacokinetics analysis was performed using a nonlinear mixed-effects modeling method. A Monte Carlo simulation was conducted to optimize lamivudine dosing.

Results: A two-compartment model adequately described the population pharmacokinetics of lamivudine. The typical population estimate for apparent clearance was 28.3 L/h. Creatinine clearance was identified as a significant factor influencing apparent clearance. According to the Monte Carlo simulation, patients with creatinine clearance between 50 and 70 mL/min should receive lamivudine 200 mg every 24 h or 300 mg every 36 h, to achieve optimal lamivudine exposure.

Conclusions: No obvious ethnic differences were observed in lamivudine pharmacokinetics between Chinese and Caucasian populations. Additionally, a model-informed dosage regimen is recommended for patients with impaired renal function.
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http://dx.doi.org/10.1080/17512433.2022.2078306DOI Listing
May 2022

Distribution of mercury and methylmercury in river water and sediment of typical manganese mining area.

J Environ Sci (China) 2022 Sep 29;119:11-22. Epub 2021 Dec 29.

College of Resources and Environment, Southwest University, Chongqing 400715, China. Electronic address:

Manganese (Mn) ores contain substantial concentrations of mercury (Hg), and mining and smelting of Mn ores can bring Hg into the surrounding aquatic environment through atmospheric deposition, leaching of electrolytic Mn residue and Mn gangue dump. However, limited is known that how these processes influence the environmental behaviors of Hg in waterbody. Therefore, the seasonal distribution and existing form of Hg in water and sediment in one Mn ore area in Xiushan County, Chongqing were investigated. Our results showed that the mean Hg and methylmercury (MeHg) concentrations in water (n=35) were 5.8 ± 4.6 ng/L and 0.22 ± 0.14 ng/L, respectively. The mean Hg concentrations in retained riverbed and fluvial bank sediment (n=35) were 0.74 ± 0.26 mg/kg and 0.63 ± 0.27 mg/kg, respectively (the mean MeHg concentrations were 0.64 ± 0.40 µg/kg and 0.51 ± 0.30 µg/kg, respectively). It indicated that the mining and smelting of Mn ores were the main sources of anthropogenic Hg, and Mn may inhibit Hg methylation in rivers in Mn ore areas. Mercury in the bound to iron/ Mn (Fe/Mn) oxides of low crystallinity fraction (Hg-OX) accounted for 4.01% and 5.25% of the total Hg concentrations in the retained riverbed and fluvial bank sediment, respectively. The amount of Hg bound to Fe/Mn oxides in sediment increased significantly due to the manganese mining activities in the investigated area. Therefore, it could be hypothesized that high Hg concentrations in river sediment in Mn mining areas are closely related to high Mn concentration in sediment.
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http://dx.doi.org/10.1016/j.jes.2021.12.011DOI Listing
September 2022

Altered anterior insula-superior frontal gyrus functional connectivity is correlated with cognitive impairment following total sleep deprivation.

Biochem Biophys Res Commun 2022 Jul 31;624:47-52. Epub 2022 Jul 31.

Ningxia Key Laboratory of Cerebrocranial Disease, Ningxia Medical University, Yinchuan, Ningxia, China. Electronic address:

Sleep deprivation is an important cause of cognitive impairment, and anterior insular subregions are core brain regions linked to cognitive function. However, the relationship between anterior insular subregions functional connectivity (FC) and the cognitive impairment that occurs following total sleep deprivation (TSD) remains unknown. As such, this study was designed to evaluate how such anterior insular subregions FC alterations are linked with impaired cognitive activity after TSD. This study recruited 20 healthy volunteers who underwent two rounds of resting-state functional magnetic resonance imaging (rs-fMRI), with one being conducted while in a state of rested wakefulness (RW) and the other being conducted following 24 h of TSD. These rs-fMRI data were then used to conduct seed-based FC analyses for the bilateral anterior insular subregions, including the dorsal anterior insula (dAI) and the ventral anterior insula (vAI). The Psychomotor Vigilance Test (PVT) was used to gauge cognitive performance, and associations between altered FC in these anterior insular subregions and PVT performance following TSD were measured using Pearson correlation analyses. Significant changes in the FC of these bilateral insular subregions were observed following 24 h of TSD relative to the RW state. Significantly enhanced FC was evident between the left dAI and right superior frontal gyrus (SFG), right dAI and bilateral SFG and right putamen, and right vAI and left medial SFG. Moreover, the observed enhancement of FC between the left vAI and right SFG functional connectivity was positively correlated with worse PVT performance. These data suggest that altered FC in the anterior insular subregions represents a prominent neuroimaging biomarker associated with cognitive impairment following TSD.
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http://dx.doi.org/10.1016/j.bbrc.2022.07.078DOI Listing
July 2022

Decentralized Federated Averaging.

IEEE Trans Pattern Anal Mach Intell 2022 Aug 4;PP. Epub 2022 Aug 4.

Federated averaging (FedAvg) is a communication-efficient algorithm for distributed training with an enormous number of clients. In FedAvg, clients keep their data locally for privacy protection; a central parameter server is used to communicate between clients. This central server distributes the parameters to each client and collects the updated parameters from clients. FedAvg is mostly studied in centralized fashions, requiring massive communications between the central server and clients, which leads to possible channel blocking. Moreover, attacking the central server can break the whole system's privacy. Indeed, decentralization can significantly reduce the communication of the busiest node (the central one) because all nodes only communicate with their neighbors. To this end, in this paper, we study the decentralized FedAvg with momentum (DFedAvgM), implemented on clients that are connected by an undirected graph. In DFedAvgM, all clients perform stochastic gradient descent with momentum and communicate with their neighbors only. To further reduce the communication cost, we also consider the quantized DFedAvgM. The proposed algorithm involves the mixing matrix, momentum, client training with multiple local iterations, and quantization, introducing extra items in the Lyapunov analysis. Thus, the analysis of this paper is much more challenging than previous decentralized (momentum) SGD or FedAvg. We prove convergence of the (quantized) DFedAvgM under trivial assumptions; the convergence rate can be improved to sublinear when the loss function satisfies the PŁ property. Numerically, we find that the proposed algorithm outperforms FedAvg in both convergence speed and communication cost.
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http://dx.doi.org/10.1109/TPAMI.2022.3196503DOI Listing
August 2022

RNA editing underlies genetic risk of common inflammatory diseases.

Nature 2022 Aug 3. Epub 2022 Aug 3.

Department of Genetics, Stanford University, Stanford, CA, USA.

A major challenge in human genetics is to identify the molecular mechanisms of trait-associated and disease-associated variants. To achieve this, quantitative trait locus (QTL) mapping of genetic variants with intermediate molecular phenotypes such as gene expression and splicing have been widely adopted. However, despite successes, the molecular basis for a considerable fraction of trait-associated and disease-associated variants remains unclear. Here we show that ADAR-mediated adenosine-to-inosine RNA editing, a post-transcriptional event vital for suppressing cellular double-stranded RNA (dsRNA)-mediated innate immune interferon responses, is an important potential mechanism underlying genetic variants associated with common inflammatory diseases. We identified and characterized 30,319 cis-RNA editing QTLs (edQTLs) across 49 human tissues. These edQTLs were significantly enriched in genome-wide association study signals for autoimmune and immune-mediated diseases. Colocalization analysis of edQTLs with disease risk loci further pinpointed key, putatively immunogenic dsRNAs formed by expected inverted repeat Alu elements as well as unexpected, highly over-represented cis-natural antisense transcripts. Furthermore, inflammatory disease risk variants, in aggregate, were associated with reduced editing of nearby dsRNAs and induced interferon responses in inflammatory diseases. This unique directional effect agrees with the established mechanism that lack of RNA editing by ADAR1 leads to the specific activation of the dsRNA sensor MDA5 and subsequent interferon responses and inflammation. Our findings implicate cellular dsRNA editing and sensing as a previously underappreciated mechanism of common inflammatory diseases.
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http://dx.doi.org/10.1038/s41586-022-05052-xDOI Listing
August 2022

Trend estimation and short-term forecasting of COVID-19 cases and deaths worldwide.

Proc Natl Acad Sci U S A 2022 Aug 3;119(32):e2112656119. Epub 2022 Aug 3.

Swiss Data Science Center, École Polytechnique Fédérale de Lausanne and Eidgenössische Technische Hochschule Zürich, 1015 Lausanne, Switzerland.

Since the beginning of the COVID-19 pandemic, many dashboards have emerged as useful tools to monitor its evolution, inform the public, and assist governments in decision-making. Here, we present a globally applicable method, integrated in a daily updated dashboard that provides an estimate of the trend in the evolution of the number of cases and deaths from reported data of more than 200 countries and territories, as well as 7-d forecasts. One of the significant difficulties in managing a quickly propagating epidemic is that the details of the dynamic needed to forecast its evolution are obscured by the delays in the identification of cases and deaths and by irregular reporting. Our forecasting methodology substantially relies on estimating the underlying trend in the observed time series using robust seasonal trend decomposition techniques. This allows us to obtain forecasts with simple yet effective extrapolation methods in linear or log scale. We present the results of an assessment of our forecasting methodology and discuss its application to the production of global and regional risk maps.
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http://dx.doi.org/10.1073/pnas.2112656119DOI Listing
August 2022

Accurate and robust registration method for computer-assisted high tibial osteotomy surgery.

Int J Comput Assist Radiol Surg 2022 Aug 2. Epub 2022 Aug 2.

Key Laboratory of Mechanism Theory and Equipment Design of Ministry of Education, Tianjin University, Tianjin, 300354, China.

Purpose: Computer-assisted high tibial osteotomy (HTO) is a frequently used treatment technique for lower extremity orthopedics, and its small incision and low exposure area are major limitations in tibial registration. This work combines skin surface features and gives a suitable registration algorithm based on Iterative Closest Points (ICP) algorithm to improve registration results. Furthermore, the precision, stability and efficiency of the described method is evaluated.

Methods: After the initialization stage, the bone surface and skin surface data are combined to construct registration features. Then, a steepest perturbation search method is performed after the ICP algorithm (SPS-ICP) to obtain the optimal transformation through several iterations. Finally, the registration result is evaluated by establishing ground-truth through manual landmarks.

Results: Phantom experiments including simulated human tissue show that the proximal fiducial registration error (FRE) of our method can reach 0.80 ± 0.30 mm (mean ± SD) with an overall rotational error < 1° and translational error < 1.5 mm. Furthermore, it remains stable when the point set is sparse. The average registration time is less than 40 s to ensure the high efficiency of surgical operation.

Conclusions: The approach fully describes a well-defined framework without additional imaging acquisition equipment for Computer-assisted HTO. By the experiment on the basis of a phantom with simulated soft tissue, the proposed method enables the accurate and robust registration of the tibia, and its computation time meets the demands of surgery.
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http://dx.doi.org/10.1007/s11548-022-02720-1DOI Listing
August 2022

Transcriptomic Profile Identifies Hippocampal Sgk1 as the Key Mediator of Ovarian Estrogenic Regulation on Spatial Learning and Memory and Aβ Accumulation.

Neurochem Res 2022 Aug 1. Epub 2022 Aug 1.

Department of Neurobiology, Army Medical University, Chongqing, 400038, China.

Previous studies have shown that ovarian estrogens are involved in the occurrence and pathology of Alzheimer's disease (AD) through regulation on hippocampal synaptic plasticity and spatial memory; however, the underlying mechanisms have not yet been elucidated at the genomic scale. In this study, we established the postmenopausal estrogen-deficient model by ovariectomy (OVX). Then, we used high-throughput Affymetrix Clariom transcriptomics and found 143 differentially expressed genes in the hippocampus of OVX mice with the absolute fold change ≥ 1.5 and P < 0.05. GO analysis showed that the highest enrichment was seen in long-term memory. Combined with the response to steroid hormone enrichment and GeneMANIA network prediction, the serum and glucocorticoid-regulated kinase 1 gene (Sgk1) was found to be the most potent candidate for ovarian estrogenic regulation. Sgk1 overexpression viral vectors (oSgk1) were then constructed and injected into the hippocampus of OVX mice. Morris water maze test revealed that the impaired spatial learning and memory induced by OVX was rescued by Sgk1 overexpression. Additionally, the altered expression of synaptic proteins and actin remodeling proteins and changes in CA1 spine density and synapse density induced by OVX were also significantly reversed by oSgk1. Moreover, the OVX-induced increase in Aβ-producing BACE1 and Aβ and the decrease in insulin degrading enzyme were significantly reversed by oSgk1. The above results show that multiple pathways and genes are involved in ovarian estrogenic regulation of the function of the hippocampus, among which Sgk1 may be a novel potent target against estrogen-sensitive hippocampal dysfunctions, such as Aβ-initiated AD.
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http://dx.doi.org/10.1007/s11064-022-03690-1DOI Listing
August 2022

Gut Microbes in Gynecologic Cancers: Causes or Biomarkers and Therapeutic Potential.

Front Oncol 2022 13;12:902695. Epub 2022 Jul 13.

Department of Breast Medicine, Cancer Hospital of China Medical University, Liaoning Cancer Hospital, Shenyang, China.

The human intestine is home to a variety of microorganisms. In healthy populations, the intestinal flora shares a degree of similarity and stability, and they have a role in the metabolism, immunological response, and physiological function of key organs. With the rapid advent of high-throughput sequencing in recent years, several researchers have found that dysbiosis of the human gut microflora potentially cause physical problems and gynecological malignancies among postmenopausal women. Besides, dysbiosis hinders tumor treatment. Nonetheless, the importance of maintaining homeostatic gut microbiota and the effective use of probiotics in the treatment of gynecological malignancies should not be disregarded. Moreover, intestinal flora regulation and the involvement of probiotics as well as associated biologically active substances in gynecological malignancies could be an adjuvant treatment modality related to surgery and chemoradiotherapy in the future. Herein, this article aims to review the potential relationship between gut microorganisms and postmenopausal status as well as gynecologic malignancies; then the relationship between gut microbes and early screening as well as therapeutic aspects. Also, we describe the role of probiotics in the prevention, treatment, and prognosis of gynecologic malignancies.
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http://dx.doi.org/10.3389/fonc.2022.902695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9326394PMC
July 2022

Cold Plasma Irradiation Attenuates Atopic Dermatitis Enhancing HIF-1α-Induced MANF Transcription Expression.

Front Immunol 2022 14;13:941219. Epub 2022 Jul 14.

Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, China.

Cold atmospheric plasma has been widely applied in medical treatment clinically, especially skin diseases. However, the mechanism of cold atmospheric plasma on the treatment of skin diseases is still undefined. In this study, dinitrofluorobenzene-induced atopic dermatitis mice model was constructed. Cold atmospheric plasma was able to decrease skin cells apoptosis, relieve skin inflammation, ER stress and oxidative stress caused by dinitrofluorobenzene stimulation, which was mediated by cold atmospheric plasma-induced MANF expression. In terms of mechanism, hypoxia-inducible factor-1α expression was increased intracellularly after cold atmospheric plasma treatment, which further bound to the promoter region of gene and enhanced MANF transcriptional expression. This study reveals that cold atmospheric plasma has a positive effect on atopic dermatitis treatment, also demonstrates the regulatory mechanism of cold atmospheric plasma on MANF expression HIF-1α, which indicates the potential medical application of cold atmospheric plasma for atopic dermatitis treatment.
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http://dx.doi.org/10.3389/fimmu.2022.941219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9329666PMC
August 2022

Coexistence under Hierarchical Resource Exploitation: The Role of the *-Preemption Trade-Off.

Am Nat 2022 08 27;200(2):193-201. Epub 2022 Jun 27.

AbstractResource competition theory predicts coexistence and exclusion patterns based on species' *s, the minimum resource values required for a species to persist. A central assumption of the theory is that all species have equal access to resources. However, many systems are characterized by preemption exploitation, where some species deplete resources before their competitors can access them (e.g., asymmetric light competition, contest competition among animals). We hypothesized that coexistence under preemption requires an *-preemption trade-off-that is, the species with the priority access should have a higher * (lower "efficiency"). Thus, we developed an extension of resource competition theory to investigate partial and total preemption (in the latter, the preemptor is unaffected by species with lower preemption rank). We found that an *-preemption trade-off is a necessary condition for coexistence in all models. Moreover, under total preemption, the trade-off alone is sufficient for coexistence. In contrast, under partial preemption, more conditions are needed, which restricts the parameter space of coexistence. Finally, we discuss the implications of our finding for seemingly distinct trade-offs, which we view as special cases of the *-preemption trade-off. These trade-offs include the digger-grazer trade-off, the competition-colonization trade-off, and trade-offs related to light competition between trees and understories.
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http://dx.doi.org/10.1086/720269DOI Listing
August 2022

Enlarged Pericarotid Lymph Nodes Suggest Recent Ischemic Symptoms in Patients with Carotid Atherosclerosis.

Front Immunol 2022 12;13:900642. Epub 2022 Jul 12.

Department of Neurosurgery, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong University, Jinan, China.

Atherosclerosis is a chronic inflammatory disease closely associated with immunological activity. Lymph nodes (LNs) are essential secondary lymphoid organs, in which complex immune responses occur. Enlarged LNs are commonly observed around inflamed tissues or tumors; however, their role in atherosclerosis is not well understood. We hypothesized that enlarged pericarotid LNs would be present in symptomatic patients with carotid atherosclerosis. Therefore, we recorded the size of LNs around the carotid artery during surgery in patients undergoing carotid endarterectomy (CEA) for carotid atherosclerotic stenosis. Patients were stratified by enlarged LNs, defined as a diameter ≥ 10mm in the transverse diameters. Demographic and clinical data of participants were measured and analyzed. Hematoxylin and eosin (H&E), Sirius red, DAB-enhanced Perls' Prussian blue, alizarin red, and immunohistochemistry (IHC) staining were performed for composition identification of plaques or LNs. Symptomatic patients were defined as those presenting with an ipsilateral cerebral ischemic event. Compared with patients with non-enlarged LNs, patients with enlarged LNs were more likely to be symptomatic (22/32, 68.8% versus 9/40, 22.5%, < 0.001) and use calcium channel blocker drugs (17/32, 53.1% versus 10/40, 25%, =0.014). In addition, they showed lower body mass index (mean ± SD: 24.00 ± 2.66 versus 25.34 ± 2.56 kg/m, =0.034), lower weight (median [interquartile range]: 64 [60.00-76.00] versus 72.5 [65.00-77.50] Kg, = 0.046) and higher diastolic blood pressure (mean ± SD: 78.94 ± 9.30 versus 73.93 ± 8.84 mmHg, = 0.022). The plague from patients with enlarged LNs exhibited a lower relative percentage of fibrous tissue (29.49 ± 10.73% versus 34.62 ± 10.33%, = 0.041). The enlarged LNs remained oval-shaped by visual inspection. Compared to non-enlarged LNs, the predominant changes in enlarged LNs were atrophic lymphatic sinuses and dilated LNs parenchyma. Enlarged LNs contained more germinal centers and lymphocytes. In conclusion, symptomatic patients with carotid atherosclerosis have enlarged pericarotid LNs. The current study supports the conclusion that enlarged LNs with an activated and enhanced adaptive immune response may indicate plaque instability. Pericarotid LNs will be a promising marker of plaque stability and may be a potential therapeutic target in patients with carotid atherosclerosis.
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http://dx.doi.org/10.3389/fimmu.2022.900642DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9315152PMC
August 2022

Microvascular decompression for trigeminal neuralgia caused by persistent trigeminal artery associated with craniosynostosis: a case report.

J Med Case Rep 2022 Jul 29;16(1):292. Epub 2022 Jul 29.

Department of Neurosurgery, The First Affiliated Hospital of Sun Yat-Sen University, No 58th, Zhongshan Er Road, Guangzhou, 510080, China.

Background: Persistent trigeminal artery (PTA) is a rare arterial anastomosis between the basilar artery (BA) and internal carotid artery (ICA). It plays an indispensable role in a number of neurological disorders, including trigeminal neuralgia (TN).

Case Presentation: We report a unique case of a 58-year-old Han female patient with TN caused by PTA associated with craniosynostosis. Preoperative three-dimensional time-of-flight (3D-TOF) magnetic resonance (MR) and 3D constructive inference in steady state (3D-CISS) imaging showed that the PTA run though Meckel's cave. Complete pain relief was immediately achieved after microvascular decompression (MVD), without facial numbness and other complications. No recurrence was recorded at the 1-year follow up.

Conclusions: Microvascular decompression is a feasible option for the treatment of complex TN combined with other abnormalities. For patients deemed suitable for percutaneous balloon compression, PTA should be ruled out. Preoperative 3D-TOF and 3D-CISS MR imaging were essential to identify PTA neurovascular conflicts.
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http://dx.doi.org/10.1186/s13256-022-03490-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9336082PMC
July 2022

Mechanical Properties, Constitutive Behaviors and Failure Criteria of Al-PTFE-W Reactive Materials with Broad Density.

Materials (Basel) 2022 Jul 26;15(15). Epub 2022 Jul 26.

Beijing Institute of Technology, 5 South Zhongguancun Street, Beijing 100081, China.

Quasi-static tension tests, quasi-static compression tests and dynamic compression tests were conducted to investigate the mechanical properties, constitutive behaviors and failure criteria of aluminum-polytetrafluoroethylene-tungsten (Al-PTFE-W) reactive materials with W content from 20% to 80%. The analysis of the quasi-static test results indicated that the strength of the materials may be independent of the stress state and W content. However, the compression plasticity of the materials is significantly superior to its tension plasticity. W content has no obvious influence on the compression plasticity, while tension plasticity is extremely sensitive to W content. Dynamic compression test results demonstrated the strain rate strengthening effect and the thermal softening effect of the materials, yet the dynamic compression strengths and the strain rate sensitivities of the materials with different W content show no obvious difference. Based on the experimental results and numerical iteration, the Johnson-Cook constitutive (, , , and ) and failure parameters (~) were well determined. The research results will be useful for the numerical studies, design and application of reactive materials.
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http://dx.doi.org/10.3390/ma15155167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9332727PMC
July 2022

Characterization of plasma exosomal microRNAs in responding to radiotherapy of human esophageal squamous cell carcinoma.

Mol Med Rep 2022 Sep 27;26(3). Epub 2022 Jul 27.

Center for Precision Medicine, School of Medicine and School of Biomedical Sciences, Huaqiao University, Xiamen, Fujian 361021, P.R. China.

Radiotherapy is one of the main treatment methods for esophageal squamous cell carcinoma (ESCC). Previous research has shown that plasma exosomal microRNAs (miRNAs) can predict therapeutic outcome. In the present study, to identify potential exosomal miRNAs that respond to radiotherapy, plasma exosomal miRNAs from ESCC patients undergoing radiotherapy were isolated and sequenced. Upregulated and downregulated miRNAs were detected from patients pre‑ and post‑radiotherapy, and it was found that they play distinct roles in DNA damage process and endosomal mediated transport. Based on wound healing and Cell Counting Kit‑8 assays in TE‑1 human esophageal cancer cells, it was identified that representative miRNA and alter migration but not proliferation. The present findings identified differentially expressed miRNAs in responding to radiotherapy, and added a reference to explore non‑invasive plasma biomarkers to evaluate therapeutic effects in ESCC.
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http://dx.doi.org/10.3892/mmr.2022.12803DOI Listing
September 2022

Acute Effects of Focused Ultrasound-Induced Blood-Brain Barrier Opening on Anti-Pyroglu3 Abeta Antibody Delivery and Immune Responses.

Biomolecules 2022 07 6;12(7). Epub 2022 Jul 6.

Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, 60 Fenwood Road, Boston, MA 02115, USA.

Alzheimer's Disease (AD) is a neurodegenerative disorder characterized by the accumulation of amyloid plaques and hyperphosphorylated tau in the brain. Currently, therapeutic agents targeting amyloid appear promising for AD, however, delivery to the CNS is limited due to the blood-brain-barrier (BBB). Focused ultrasound (FUS) is a method to induce a temporary opening of the BBB to enhance the delivery of therapeutic agents to the CNS. In this study, we evaluated the acute effects of FUS and whether the use of FUS-induced BBB opening enhances the delivery of 07/2a mAb, an anti-pyroglutamate-3 Aβ antibody, in aged 24 mo-old APP/PS1dE9 transgenic mice. FUS was performed either unilaterally or bilaterally with mAb infusion and the short-term effect was analyzed 4 h and 72 h post-treatment. Quantitative analysis by ELISA showed a 5-6-fold increase in 07/2a mAb levels in the brain at both time points and an increased brain-to-blood ratio of the antibody. Immunohistochemistry demonstrated an increase in IgG2a mAb detection particularly in the cortex, enhanced immunoreactivity of resident Iba1+ and phagocytic CD68+ microglial cells, and a transient increase in the infiltration of Ly6G+ immune cells. Cerebral microbleeds were not altered in the unilaterally or bilaterally sonicated hemispheres. Overall, this study shows the potential of FUS therapy for the enhanced delivery of CNS therapeutics.
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http://dx.doi.org/10.3390/biom12070951DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9313174PMC
July 2022

[Reform of biology experiment teaching in the context of "Strengthening Basic Disciplines Program"-taking the course of comprehensive biology design as an example].

Sheng Wu Gong Cheng Xue Bao 2022 Jul;38(7):2655-2664

School of Life Sciences, Tianjin University, Tianjin 300072, China.

Talent training is the core of future national competition. "Strengthening Basic Disciplines Program" is an important initiative exploring the training mode for top-notch creative talents in basic disciplines, and an important measure to meet the needs for fostering future talents. The students enrolled in the "Strengthening Basic Disciplines Program" often have excellent grades and strong motivation, which puts forward new requirements and new goals for the talents training mode. Among them, the teaching reform under the background of "Strengthening Basic Disciplines Program" is imperative. The science, technology, engineering, arts, mathematics (STEAM) education concept is an interdisciplinary comprehensive educational philosophy that happens to coincide with the philosophy of the "Strengthening Basic Disciplines Program". In view of this, the School of Life Sciences of Tianjin University has explored and practiced the reform of biology experimental teaching based on the objective of fostering biology talents in the context of "Strengthening Basic Disciplines Plan" and the STEAM education concept, by taking the course of comprehensive biology design as an example.
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http://dx.doi.org/10.13345/j.cjb.210953DOI Listing
July 2022

[Application of synthetic small regulatory RNAs in synthetic biology].

Sheng Wu Gong Cheng Xue Bao 2022 Jul;38(7):2459-2476

Laboratory of Synthetic Microbiology, School of Chemical Engineering & Technology, Tianjin University, Tianjin 300072, China.

Synthetic biology has brought enormous impacts to the advancement of agriculture, energy, manufacturing and medicine by redesigning existing natural systems or creating biological elements, modules and systems to endow life with new functions. The precise, quantitative and efficient regulation of biological elements, modules and systems is critical for controlling living systems. Bacterial small regulatory RNAs are a class of functional molecules with a length of 50-300 nt and usually do not translate into proteins. They play an irreplaceable role in environmental stress response, metabolic adaptation and bacterial virulence control. In recent years, synthetic small regulatory RNAs have been designed based on natural small RNAs and were used to effectively inhibit or activate target genes and even pathways. Synthetic small regulatory RNAs have broad application advantages in synthetic biology because of their small size, high flexibility, programmability, easy design and little metabolic burden on host cells. To better understand the synthetic small regulatory RNAs and promote its application, this review summarized several synthetic small RNA systems and their representative applications in synthetic biology. Finally, future optimization directions were prospected.
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http://dx.doi.org/10.13345/j.cjb.220068DOI Listing
July 2022

EMX1 functions as a tumor inhibitor in spinal cord glioma through transcriptional suppression of WASF2 and inactivation of the Wnt/β-catenin axis.

Brain Behav 2022 Jul 18:e2684. Epub 2022 Jul 18.

Department of Traumatic Orthopedics, Yantaishan Hospital of Yantai, Yantai, Shandong, P.R. China.

Background: Gliomas are the most frequent and aggressive cancers in the central nervous system, and spinal cord glioma (SCG) is a rare class of the gliomas. Empty spiracles homobox genes (EMXs) have shown potential tumor suppressing roles in glioma, but the biological function of EMX1 in SCG is unclear.

Methods: The EMX1 expression in clinical tissues of patients with SCG was examined. SCG cells were extracted from the tissues, and altered expression of EMX1 was then introduced to examine the role of EMX1 in cell growth and invasiveness in vitro. Xenograft tumors were induced in nude mice for in vivo validation. The targets of EXM1 were predicted via bioinformatic analysis and validated by luciferase and ChIP-qPCR assays. Rescue experiments were conducted to validate the involvements of the downstream molecules.

Results: EMX1 was poorly expressed in glioma, which was linked to decreased survival rate of patients according to the bioinformatics prediction. In clinical tissues, EMX1 was poorly expressed in SCG, especially in the high-grade tissues. EMX1 upregulation significantly suppressed growth and metastasis of SCG cells in vitro and in vivo. EMX1 bound to the promoter of WASP family member 2 (WASF2) to suppress its transcription. Restoration of WASF2 blocked the tumor-suppressing effect of EMX1. EMX1 suppressed Wnt/β-catenin signaling activity by inhibiting WASF2. Coronaridine, a Wnt/β-catenin-specific antagonist, blocked SCG cell growth and metastasis induced by WASF2.

Conclusion: This study elucidates that EMX1 functions as a tumor inhibitor in SCG by suppressing WASF2-dependent activation of the Wnt/β-catenin axis.
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http://dx.doi.org/10.1002/brb3.2684DOI Listing
July 2022

Comparison of MLC positioning deviations using log files and establishment of specific assessment parameters for different accelerators with IMRT and VMAT.

Radiat Oncol 2022 Jul 16;17(1):123. Epub 2022 Jul 16.

Department of Radiation Physics and Technology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, 440 Jiyan Road, Jinan, 250117, Shandong, China.

Background And Purpose: The study evaluated the differences in leaf positioning deviations by the log files of three advanced accelerators with two delivery techniques, and established specific assessment parameters of leaf positioning deviations for different types of accelerators.

Methods: A total of 420 treatment plans with 5 consecutive treatment log files were collected from the Trilogy, TrueBeam and Halcyon accelerators. Millennium MLC was equipped on the Trilogy and TrueBeam accelerators. A jawless design and dual-layer MLC were adopted on the Halcyon accelerator. 70 IMRT and 70 VMAT plans were selected randomly on each accelerator. The treatment sites of all plans included head and neck, chest, breast, pelvis and other sites. The parsing tasks for 2100 log files were proceeded by SunCheck software from Sun Nuclear Corporation. The maximum leaf root mean square (RMS) errors, 95th percentile errors and percentages of different leaf positioning errors were statistically analyzed. The correlations between these evaluation parameters and accelerator performance parameters (maximum leaf speed, mean leaf speed, gantry and arc angle) were analyzed.

Results: The average maximum leaf RMS errors of the Trilogy in the IMRT and VMAT plans were 0.44 ± 0.09 mm and 0.79 ± 0.07 mm, respectively, which were higher than the TrueBeam's 0.03 ± 0.01 mm, 0.03 ± 0.01 mm and the Halcyon's 0.05 ± 0.01 mm, 0.07 ± 0.01 mm. Similar data results were shown in the 95th percentile error. The maximum leaf RMS errors were strongly correlated with the 95th percentile errors (Pearson index > 0.5). The leaf positioning deviations in VMAT were higher than those in IMRT for all accelerators. In TrueBeam and Halcyon, leaf position errors above 1 mm were not found in IMRT and VMAT plans. The main influencing factor of leaf positioning deviation was the leaf speed, which has no strong correlation with gantry and arc angles.

Conclusions: Compared with the quality assurance guidelines, the MLC positioning deviations tolerances of the three accelerators should be tightened. For both IMRT and VMAT techniques, the 95th percentile error and the maximum RMS error are suggested to be tightened to 1.5 and 1 mm respectively for the Trilogy accelerator. In TrueBeam and Halcyon accelerators, the 95th percentile error and maximum RMS error of 1 and 0.5 mm, respectively, are considered appropriate.
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http://dx.doi.org/10.1186/s13014-022-02097-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9288677PMC
July 2022

A Global Perspective of Correlation Between Maternal Copper Levels and Preeclampsia in the 21st Century: A Systematic Review and Meta-Analysis.

Front Public Health 2022 27;10:924103. Epub 2022 Jun 27.

Department of Obstetrics, Center for Reproductive Medicine, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, China.

Background: Preeclampsia (PE) is a common multi-system disorder in pregnancy and a major cause of maternal and perinatal morbidity and mortality globally. Copper is a crucial micronutrient for human health.

Methods: A systematic review was performed according to Preferred Reporting Item for Systematic Reviews and Meta-analysis (PRISMA) guidelines to synthesize the best available evidence regarding the correlation between maternal copper levels and PE from women with different geographical and economic backgrounds.

Results: A total of 34 studies containing 2,471 women with PE and 2,888 healthy pregnant controls across 16 countries were included for research. All studies were systematically reviewed and assessed with the Newcastle-Ottawa Scale (NOS), The Agency of Healthcare for Research and Quality (AHRQ) assessment tools according to the study types. Globally, there was no significant difference in maternal serum copper levels between women with PE and control (Mean difference 5.46, 95% CI -9.63, 20.54). Sub-group analysis from geographical and economic perspectives revealed contrasting results. In conclusion, copper is associated with PE, but the levels of copper leading to increased risk of PE varied across regions and economic development.

Conclusions: The deranged maternal copper levels are correlated with risks of PE, but it presents variously across different geographical and economic contexts.

Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=306536. Identifier: CRD42022306536.
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http://dx.doi.org/10.3389/fpubh.2022.924103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9271744PMC
July 2022

Breast cancer brain metastasis: Current evidence and future directions.

Cancer Med 2022 Jul 13. Epub 2022 Jul 13.

Department of Medical Oncology, Liaoning Cancer Hospital & Institute, Cancer Hospital of China Medical University, Shenyang, China.

Breast cancer is the most common cancer in women and the second leading cause of cancer-related deaths after lung cancer. Metastasis of the central nervous system is a terrible event for breast cancer patients, affecting their survival and quality of life. Compared with hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancer patients, brain metastases are more likely to affect patients with triple-negative breast cancer and human epidermal growth factor receptor 2-positive breast cancer. The treatment of breast cancer has improved greatly in the last two decades. However, brain metastases from breast cancer remain the leading cause of morbidity and mortality. Patients with breast cancer brain metastasis have been in an inferior position due to the lack of clinical research in this field, and they are often explicitly excluded from almost all clinical trials. The occurrence and progression of brain metastases will result in severe cognitive impairment and adverse physical consequences, so we must have a good understanding of the molecular mechanisms of breast cancer brain metastasis. In this article, we have retrieved the latest literature of molecules and pathways associated with breast cancer brain metastasis, summarized common therapy strategies, and discussed the prospects and clinical implications of targeting the molecules involved.
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http://dx.doi.org/10.1002/cam4.5021DOI Listing
July 2022

A randomized phase 3 trial of Gemcitabine or Nab-paclitaxel combined with cisPlatin as first-line treatment in patients with metastatic triple-negative breast cancer.

Nat Commun 2022 Jul 12;13(1):4025. Epub 2022 Jul 12.

Department of Breast Cancer and Urological Medical Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong'an Road, Shanghai, 200032, P.R. China.

Platinum is recommended in combination with gemcitabine in the treatment of metastatic triple-negative breast cancer (mTNBC). We conduct a randomized phase 3, controlled, open-label trial to compare nab-paclitaxel/cisplatin (AP) with gemcitabine/cisplatin (GP) in mTNBC patients (ClinicalTrials.gov NCT02546934). 254 patients with untreated mTNBC randomly receive AP (nab-paclitaxel 125 mg/m² on day 1, 8 and cisplatin 75 mg/m² on day 1) or GP (gemcitabine 1250 mg/m² on day 1, 8 and cisplatin 75 mg/m² on day 1) intravenously every 3 weeks until progression disease, intolerable toxicity or withdrawal of consent. The primary endpoint is progression-free survival (PFS); secondary endpoints are objective response rate (ORR), safety and overall survival (OS). The trial has met pre-specified endpoints. The median PFS is 9.8 months with AP as compared to 7.4 months with GP (stratified HR, 0.67; 95% CI, 0.50-0.88; P = 0.004). AP significantly increases ORR (81.1% vs. 56.3%, P < 0.001) and prolongs OS (stratified HR, 0.62; 95% CI, 0.44-0.90; P = 0.010) to GP. Of grade 3 or 4 adverse events, a significantly higher incidence of neuropathy in AP and thrombocytopenia in GP is noted. These findings warrant further assessment of adding novel agents to the nab-paclitaxel/platinum backbone due to its high potency for patients with mTNBC.
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http://dx.doi.org/10.1038/s41467-022-31704-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9276725PMC
July 2022

Microenvironment-tailored micelles restrain carcinoma-astrocyte crosstalk for brain metastasis.

J Control Release 2022 Jul 20;349:520-532. Epub 2022 Jul 20.

Department of Pharmaceutics, School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery, Ministry of Education, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai 201203, China. Electronic address:

Breast-to-brain metastatic cells can interact with the surrounding cells, including astrocytes and microglia, to generate a pro-tumorigenic niche. Breast-to-brain metastasis can be treated using a dual strategy of eliminating metastatic tumor cells and normalizing their localized microenvironment. The effective accumulation of drugs at the action site of metastasis is crucial to realizing the above strategy, especially when dealing with the blood-brain barrier (BBB)-penetrating and tumor-targeting tactics. Here, we establish an in-situ microenvironment-tailored micelle (T-M/siRNA) to co-deliver therapeutic siRNA and paclitaxel (PTX) into the breast-to-brain metastasis. Anchored with a D-type cyclic peptide, T-M/siRNA can penetrate the BBB and subsequently target the brain metastases. Upon internalization by metastatic tumor cells, T-M/siRNA can release PTX in the high-level glutathione (GSH), resulting in killing cancer cells. Meanwhile, the micellar structure is dissociated, resulting in lowering the charge density to release the loaded siRNA that can targeted downregulate the expression of protocadherin 7 (PCDH7). Treatment of model mice revealed that T-M/siRNA can inhibit the abnormal activation of astrocytes and immunosuppressive activation of microglia, resulting in significantly enhanced synergistic anti-tumor efficacy. This study indicates that the micelle system can serve as a hopeful strategy to treat breast-to-brain metastasis.
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http://dx.doi.org/10.1016/j.jconrel.2022.07.009DOI Listing
July 2022

Alterations of RNAs in the insula related to cocaine-induced condition place preference in adolescent mice.

Biochem Biophys Res Commun 2022 09 5;621:109-115. Epub 2022 Jul 5.

Ningxia Key Laboratory of Craniocerebral Disease, Ningxia Medical University, Yinchuan, China. Electronic address:

Cocaine as a highly addictive psychostimulant can cause changes in the body at the cellular and molecular levels over a long period of time. It reminds us that cocaine may have a potential role in post-transcriptional regulation, but the alteration of insula-expression profile in adolescent cocaine use disorder (CUD) has not been reported. To reveal the mechanisms underlying the post-transcriptional regulation of cocaine, we investigate the transcriptome in the insula of cocaine-induced mice based on high-throughput strand-specific RNA sequencing. We analyzed the alterations of messenger RNA (mRNA) expression profile in the insula of cocaine-induced condition place preference (CPP) mice and then correlated it with microRNAs to reveal their involvement in the formation of cocaine-induced CPP. In this study, a total of 27786 genes were identified, 5750 new genes (novel expressed transcripts of unannotated in the reference genome) were discovered, among which 1,205 were annotated functionally. A total of 198 differentially expressed genes (DEG) that functioned in synaptic transmission, cholinergic, developmental process, neurotransmitter metabolic process, drug catabolism, cellular response to drug, MAP kinase activity, ceramidase activity, and drug resistance were significantly enriched. Further analysis showed that 26045 mRNAs formed 45,208 network-relationship pairs with 1770 microRNAs. In the current study, our work was the first to reveal that alterations of RNAs in the insula, as a core brain region of the neural circuits of interoception, were involved in the process of cocaine-induced CPP of adolescent mice. These findings enrich the biology and expand the molecular regulatory network related to adolescence CUD. They provided the possibility that some DEGs may be used as novel biomarkers for the diagnosis or evaluation of substance use disorder, and also provided clues for elucidating the neurobiological mechanism of substance use disorder.
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http://dx.doi.org/10.1016/j.bbrc.2022.06.080DOI Listing
September 2022

Pembrolizumab for the better treatment of EGFR-mutant T790M-negative advanced lung adenocarcinoma patients than dual treatment of pemetrexed plus platinum after tyrosine kinase inhibitor treatment failure.

Ann Palliat Med 2022 Jun;11(6):2100-2109

Department of Cardiothoracic Surgery, Jiangmen Central Hospital, Jiangmen, China.

Background: The treatment of lung cancer patients, especially those with epidermal growth factor receptor (EGFR)-mutant T790M-negative adenocarcinoma, after first- or second-line tyrosine kinase inhibitor (TKI) treatment failure is challenging due to the poor prognosis and limited effectiveness of platinum two-drug chemotherapy or chemotherapy plus anti-angiogenesis therapy. It is well-known that pembrolizumab monotherapy exhibits low toxicity and long-term survival, but it is unknown in these patients.

Methods: From September 2018 to March 2021, 460 patients in Jiangmen Central Hospital were included and 82 patients with disease progression in lung adenocarcinoma who remained T790M-negative on the second biopsy were screened. Two groups were divided according to treatment status, and simple random sampling was performed to obtain 32 cases respectively. The safety of the patients was subsequently evaluated by telephone follow-up.

Results: The objective response rate (ORR) and disease control rate (DCR) in the pembrolizumab group were 15.63% and 53.13%. In the chemotherapy group, the ORR was 8.33% and the DCR was 25% (P<0.05). In the pembrolizumab group, the progression-free survival (PFS) [14.65 months, 95% confidence interval (CI): 13.03 to 16.28] was significantly higher than that of the control group (9.54 months, 95% CI: 8.43 to 10.65) (P<0.05). In the univariate analysis, programmed cell death protein 1 ligand (PD-L1) expression, smoking status, gender, and whether first-line chemotherapy was associated with survival. In the multivariate analysis, gender [P=0.001; hazard ratio (HR) 10.98, 95% CI: 2.49-46.67], first-line chemotherapy (P=0.037; HR 4.5, 95% CI: 1.1-4.81), and PD-L1 expression (P=0.039; HR 0.16, 95% CI: 0.04-0.68) were correlated with patient survival. Grade 3 or grade 4 treatment-related adverse events were not found in the pembrolizumab group, while 2 cases of grade 3 or 4 treatment-related adverse events occurred in the control group.

Conclusions: In advanced lung adenocarcinoma patients with EGFR-mutant T790M-negative after TKI treatment, pembrolizumab had a higher ORR and PFS. Pembrolizumab in women with first-line chemotherapy and PD-L1 ≥25% of those patients may have a good response and a low rate of adverse reactions. A multicenter, prospective, evidence-based study of pembrolizumab salvage therapy in those patients is warranted for posterior line treatment.
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http://dx.doi.org/10.21037/apm-22-671DOI Listing
June 2022

Dehydrocorydaline Accelerates Cell Proliferation and Extracellular Matrix Synthesis of TNFα-Treated Human Chondrocytes by Targeting Cox2 through JAK1-STAT3 Signaling Pathway.

Int J Mol Sci 2022 Jun 30;23(13). Epub 2022 Jun 30.

Center for Precision Medicine, School of Medicine and School of Biomedical Sciences, Huaqiao University, Xiamen 361021, China.

Osteoarthritis (OA) causes severe degeneration of the meniscus and cartilage layer in the knee and endangers joint integrity and function. In this study, we utilized tumor necrosis factor α (TNFα) to establish in vitro OA models and analyzed the effects of dehydrocorydaline (DHC) on cell proliferation and extracellular matrix (ECM) synthesis in human chondrocytes with TNFα treatment. We found that TNFα treatment significantly reduced cell proliferation and mRNA and protein expression levels of aggrecan and type II collagen, but caused an increase in mRNA and protein expression levels of type I collagen, matrix metalloproteinase 1/13 (MMP1/13), and prostaglandin-endoperoxide synthase 2 (PTGS2, also known as Cox2) in human chondrocytes. DHC significantly promoted the cell activity of normal human chondrocytes without showing cytotoxity. Moreover, 10 and 20 μM DHC clearly restored cell proliferation, inhibited mRNA and protein expression levels of type I collagen, MMP 1/13, and Cox2, and further increased those of aggrecan and type II collagen in the TNFα-treated human chondrocytes. RNA transcriptome sequencing indicated that DHC could improve TNFα-induced metabolic abnormalities and inflammation reactions and inhibit the expression of TNFα-induced inflammatory factors. Furthermore, we found that the JAK1-STAT3 signaling pathway was confirmed to be involved in the regulatory effects of DHC on cell proliferation and ECM metabolism of the TNFα-treated human chondrocytes. Lastly, to explore the effects of DHC in vivo, we established an anterior cruciate ligament transection (ACLT)-stimulated rat OA model and found that DHC administration significantly attenuated OA development, inhibited the enzymatic hydrolysis of ECM, and reduced phosphorylated JAK1 and STAT3 protein expression in vivo after ACLT for 6 weeks. These results suggest that DHC can effectively relieve OA progression, and it has a potential to be utilized for the clinical prevention and therapy of OA as a natural small molecular drug.
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http://dx.doi.org/10.3390/ijms23137268DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9267121PMC
June 2022
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