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The established recognition of N6-methyladenosine (m6A) modification as an indispensable regulatory agent in human cancer is widely accepted. However, the understanding of m6A's role and the mechanisms underlying its contribution to gefitinib resistance is notably limited. Herein, using RT-qPCR, Western blot, Cell proliferation and apoptosis, as well as RNA m6A modification assays, we substantiated that heightened FTO (Fat Mass and Obesity-associated protein) expression substantially underpins the emergence of gefitinib resistance in NSCLC cells. This FTO-driven gefitinib resistance is hinged upon the co-occurrence of PELI3 (Pellino E3 Ubiquitin Protein Ligase Family Member 3) expression and concurrent autophagy activation. Manipulation of PELI3 expression and autophagy activation, including its attenuation, was efficacious in both inducing and overcoming gefitinib resistance within NSCLC cells, as validated in vitro and in vivo. In summary, this study has successfully elucidated the intricate interplay involving FTO-mediated m6A modification, its consequential downstream effect on PELI3, and the concurrent involvement of autophagy in fostering the emergence of gefitinib resistance within the therapeutic context of NSCLC., Competing Interests: Declaration of competing Interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Pazopanib (PAZ), an oral multi-tyrosine kinase inhibitor, demonstrates promising cytostatic activities against various human cancers. However, its clinical utility is limited by substantial side effects and therapeutic resistance. We developed a nanoplatform capable of delivering PAZ for enhanced anti-breast cancer therapy. Nanometer-sized PAZ@Fe-MOF, compared to free PAZ, demonstrated increased anti-tumor therapeutic activities in both syngeneic murine 4T1 and xenograft human MDA-MB-231 breast cancer models. High-throughput single-cell RNA sequencing (scRNAseq) revealed that PAZ@Fe-MOF significantly reduced pro-tumorigenic M2-like macrophage populations at tumor sites and suppressed M2-type signaling pathways, such as ATF6-TGFBR1-SMAD3, as well as chemokines including CCL17, CCL22, and CCL24. PAZ@Fe-MOF reprogramed the inhibitory immune microenvironment and curbed tumorigenicity by blocking the polarization of M2 phenotype macrophages. This platform offers a promising and new strategy for improving the cytotoxicity of PAZ against breast cancers. It provides a method to evaluate the immunological response of tumor cells to PAZ-mediated treatment., (© 2024. The Author(s).)

Background: Pancreatic fibrosis is one of the most important pathological features of chronic pancreatitis (CP) and pancreatic stellate cells (PSCs) are the key cells of fibrosis. As an extracellular matrix (ECM) glycoprotein, cartilage oligomeric matrix protein (COMP) is critical for collagen assembly and ECM stability and recent studies showed that COMP exert promoting fibrosis effect in the skin, lungs and liver. However, the role of COMP in activation of PSCs and pancreatic fibrosis remain unclear. We aimed to investigate the role and specific mechanisms of COMP in regulating the profibrotic phenotype of PSCs and pancreatic fibrosis., Methods: ELISA method was used to determine serum COMP in patients with CP. Mice model of CP was established by repeated intraperitoneal injection of cerulein and pancreatic fibrosis was evaluated by Hematoxylin-Eosin staining (H&E) and Sirius red staining. Immunohistochemical staining was used to detect the expression changes of COMP and fibrosis marker such as α-SMA and Fibronectin in pancreatic tissue of mice. Cell Counting Kit-8, Wound Healing and Transwell assessed the proliferation and migration of human pancreatic stellate cells (HPSCs). Western blotting, qRT-PCR and immunofluorescence staining were performed to detect the expression of fibrosis marker, AKT and MAPK family proteins in HPSCs. RNA-seq omics analysis as well as small interfering RNA of COMP, recombinant human COMP (rCOMP), MEK inhibitors and PI3K inhibitors were used to study the effect and mechanism of COMP on activation of HPSCs., Results: ELISA showed that the expression of COMP significantly increased in the serum of CP patients. H&E and Sirius red staining analysis showed that there was a large amount of collagen deposition in the mice in the CP model group and high expression of COMP, α-SMA, Fibronectin and Vimentin were observed in fibrotic tissues. TGF-β1 stimulates the activation of HPSCs and increases the expression of COMP. Knockdown of COMP inhibited proliferation and migration of HPSCs. Further, RNA-seq omics analysis and validation experiments in vitro showed that rCOMP could significantly promote the proliferation and activation of HPSCs, which may be due to promoting the phosphorylation of ERK and AKT through membrane protein receptor CD36. rCOMP simultaneously increased the expression of α-SMA, Fibronectin and Collagen I in HPSCs., Conclusion: In conclusion, this study showed that COMP was up-regulated in CP fibrotic tissues and COMP induced the activation, proliferation and migration of PSCs through the CD36-ERK/AKT signaling pathway. COMP may be a potential therapeutic candidate for the treatment of CP. Interfering with the expression of COMP or the communication between COMP and CD36 on PSCs may be the next direction for therapeutic research., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Inflammation and immunity play important roles in the pathogenesis of ischemic stroke. This study aimed to explore key regulatory genes in acute ischemic stroke (AIS) and their underlying mechanisms to provide new research targets for the diagnosis and treatment of ischemic stroke. We searched for differentially expressed mRNAs and miRNAs in patients with AIS and healthy populations in GEO databases, constructed a miRNA-mRNA network, and screened key miRNAs using least absolute shrinkage and selection operator regression and the support vector machine-recursive feature elimination model. Correlations between key miRNAs and infiltrating immune cells and inflammatory factors were analyzed using CIBERSORT and immunoassays and verified using clinical experiments. Bioinformatics analysis identified hsa-miR-877-5p as a key regulatory miRNA in AIS that can modulate immune and inflammatory responses. In clinical studies, it was verified by quantitative PCR analysis that the expression of hsa-miR-877-5p in the blood of AIS patients was higher than that of the healthy group. Then, enzyme-linked immunosorbent assay revealed that the expression of IL-23 and TNF-α related to inflammation in AIS patients was higher than that of the healthy. Quantitative PCR further found that the relative mRNA expression of IL-23, CXCR3, and TNF-α in AIS group was higher than that of the healthy group. This study may provide a basis for a more comprehensive understanding of the potential mechanism of the occurrence and development of AIS, and hsa-miR-877-5p and its downstream effectors IL-23, CXCR3, and TNF-α may be potential intervention targets in AIS., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Pancreatic adenocarcinoma (PAAD) is a prevalent and aggressive malignancy in the digestive tract, requiring accurate prediction and effective treatment strategies. Recently, the discovery of disulfidptosis, a novel form of programmed cell death characterized by abnormal disulfide accumulation, has sparked interest in its role in PAAD. In this study, we aimed to investigate the involvement of disulfidptosis-related genes (DRGs) in PAAD. Using publicly available databases, we conducted a comprehensive analysis exploring the complex relationships between DRGs and important aspects of PAAD, including gene expression, immune response, mutation, drug sensitivity, and functional enrichment. Notably, we observed significant heterogeneity among different disulfidptosis subclusters and identified specific differentially expressed genes in PAAD. Through machine learning techniques, we identified SLC7A11, S100A4, DIAPH3, PRDX1, and SLC7A7 as the most relevant hub genes. We further validated their significance in PAAD by considering their expression patterns, prognostic value, diagnostic potential, diagnostic model, and immune infiltration. This study presents exciting opportunities and challenges in unraveling the underlying mechanisms of PAAD prognosis. It also establishes a foundation for personalized cancer care and the development of innovative immunotherapeutic strategies. By shedding light on the role of DRGs, particularly hub genes, we enhance our understanding and management of PAAD., Competing Interests: Conflict of interest: The authors declare that they have no conflict of interest to disclose., (© 2024 the author(s), published by De Gruyter.)

Objective: Photodynamic therapy (PDT) primarily treats skin diseases or cancer by generating reactive oxygen species (ROS) to damage cellular DNA, yet drug resistance limits its application. To tackle this problem, the present study was carried out to improve the efficacy of chlorin e6 (Ce6)-PDT using Cepharanthine (CEP) as well as to reveal the potential molecular mechanism., Materials and Methods: Lewis lung cancer cell line (LLC) was utilized as the cancer cell model. chlorin e6 (Ce6) acted as the photosensitizer to induce PDT. The in vitro anti-cancer efficacy was measured by CCK-8, Annexin-V/PI staining, and migration assay. The Ce6 uptake was observed using flow cytometry and confocal microscopy. The ROS generation was detected by the DCFH-DA probe. The analysis of MutT Homolog 1 (MTH1) expression, correlation, and prognosis in databases was conducted by bioinformatic. The MTH1 expression was detected through western blots (WB). DNA damage was assayed by WB, immunofluorescent staining, and comet assay., Results: Ce6-PDT showed robust resistance in lung cancer cells under certain conditions, as evidenced by the unchanged cell viability and apoptosis. The subsequent findings confirmed that the uptake of Ce6 and MTH1 expression was enhanced, but ROS generation with laser irradiation was not increased in LLC, which indicated that the ROS scavenge may be the critical reason for resistance. Surprisingly, bioinformatic and in vitro experiments identified that MTH1, which could prevent the DNA from damage of ROS, was highly expressed in lung cancer and thereby led to the poor prognosis and could be further up-regulated by Ce6 PDT. CEP exhibited a dose-dependent suppressive effect on the lung cancer cells. Further investigations presented that CEP treatment boosted ROS production, thereby resulting in DNA double-strand breakage (DDSB) with activation of MTH1, indicating that CEP facilitated Ce6-PDT-mediated DNA damage. Finally, the combination of CEP and Ce6-PDT exhibited prominent ROS accumulation, MTH1 inhibition, and anti-lung cancer efficacy, which had synergistic pro-DNA damage properties., Conclusion: Collectively, highly expressed MTH1 and the failure of ROS generation lead to PDT resistance in lung cancer cells. CEP facilitates ROS generation of PDT, thereby promoting vigorous DNA damage, inactivating MTH1, alleviating PDT resistance, and ameliorating the anti-cancer efficacy of Ce6-PDT, provides a novel approach for augmented PDT., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Objective: Prompt and effective wound repair is an essential strategy to promote recovery and prevent infection in patients with various types of trauma. Platelets can release a variety of growth factors upon activation to facilitate revascularization and tissue repair, provided that their activation is uncontrollable. The present study is designed to explore the selective activation of platelets by photodynamic and photothermal effects (PDE/PTE) as well as the trauma repair mediated by PDE/PTE., Materials and Methods: In the current research, platelets were extracted from the blood of mice. Indocyanine green (ICG) was applied to induce PDE/PTE. The uptake of ICG by platelets was detected by laser confocal microscopy and flow cytometry. The cellular integrity was measured by microscopy. The reactive oxygen species (ROS) generation and temperature of platelets were assayed by 2,7-Dichlorodihydrofluorescein diacetate (DCFH-DA) and temperature detector. The activation of platelets was measured by western blots (WB), dynamic light scattering (DLS), and scanning electron microscopy (SEM). The release of growth factor was detected by enzyme-linked immuno sorbent assay (Elisa), wherein the in vitro cell proliferation was investigated by 5-Ethynyl-2'-deoxyuridine (EDU) assay. The wound infection rates model and histological examination were constructed to assay the ICG-loaded platelet-mediated wound repair., Results: Platelets could load with ICG, a kind of photodynamic and photothermal agent, as carriers and remain intact. Near-infrared (NIR) laser irradiation of ICG-loaded platelets (ICG@PLT) facilitated higher temperature and ROS generation, which immediately activated ICG@PLT, as characterized by increased membrane p-selectin (CD62p), cyclooxygenase-2 (COX-2), thromboxane A2 receptor (TXA2R) expression, elevated hydrated particle size, and prominent aggregation in platelets. Further investigation revealed that massive insulin-like growth factor (IGF) and platelet-derived growth factor (PDGF) were released from the activated ICG@PLT, which also promoted the proliferation of endothelial cells and keratinocytes in co-culture. In consequence, activated platelets and increased neovascularization could be observed in rats with wound infection treated by ICG@PLT in the presence of NIR. More impressively, the hydrogel containing ICG@PLT accelerated wound healing and suppressed inflammation under NIR, exhibiting excellent wound repair properties., Conclusion: Taken together, the current work identified that platelets could be activated by PDE/PTE and thereby release growth factor, potentiating wound repair in a controlled manner., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Abstract: Patients with chronic pain often experience exaggerated pain response and aversive emotion, such as anxiety and depression. Central plasticity in the anterior cingulate cortex (ACC) is assumed to be a critical interface for pain perception and emotion, which has been reported to involve activation of NMDA receptors. Numerous studies have documented the key significance of cGMP-dependent protein kinase I (PKG-I) as a crucial downstream target for the NMDA receptor-NO-cGMP signaling cascade in regulating neuronal plasticity and pain hypersensitivity in specific regions of pain pathway, ie, dorsal root ganglion or spinal dorsal horn. Despite this, whether and how PKG-I in the ACC contributes to cingulate plasticity and comorbidity of chronic pain and aversive emotion has remained elusive. Here, we uncovered a crucial role of cingulate PKG-I in chronic pain and comorbid anxiety and depression. Chronic pain caused by tissue inflammation or nerve injury led to upregulation of PKG-I expression at both mRNA and protein levels in the ACC. Knockdown of ACC-PKG-I relieved pain hypersensitivity as well as pain-associated anxiety and depression. Further mechanistic analysis revealed that PKG-I might act to phosphorylate TRPC3 and TRPC6, leading to enhancement of calcium influx and neuronal hyperexcitability as well as synaptic potentiation, which results in the exaggerated pain response and comorbid anxiety and depression. We believe this study sheds new light on the functional capability of ACC-PKG-I in modulating chronic pain as well as pain-associated anxiety and depression. Hence, cingulate PKG-I may represent a new therapeutic target against chronic pain and pain-related anxiety and depression., (Copyright © 2023 International Association for the Study of Pain.)

Background and Aim: Previous studies have reported an association between gut microbiota and cirrhosis. However, the causality between intestinal flora and liver cirrhosis still remains unclear. In this study, bi-directional Mendelian randomization (MR) analysis was used to ascertain the potential causal effect between gut microbes and cirrhosis., Methods: Large-scale Genome Wide Association Study (GWAS) data of cirrhosis and gut microbes were obtained from FinnGen, Mibiogen consortium, and a GWAS meta-analysis of Alcoholic cirrhosis (ALC). Two-sample MR was performed to determine the causal relationship between gut microbiota and cirrhosis. Furthermore, a bi-directional MR analysis was employed to examine the direction of the causal relations., Result: In MR analysis, we found that 21 gut microbiotas were potentially associated with cirrhosis. In reverse MR analysis, 11 gut microbiotas displayed potentially associations between genetic liability in the gut microbiome and cirrhosis. We found that the family Lachnospiraceae (OR: 1.59, 95% CI:1.10-2.29) might be harmful in cirrhotic conditions (ICD-10: K74). Furthermore, the genus Erysipelatoclostridium might be a protective factor for cirrhosis (OR:0.55, 95% CI:0.34-0.88) and PBC (OR:0.68, 95% CI:0.52-0.89). Combining the results from the MR analysis and reverse MR analysis, we firstly identified the Genus Butyricicoccus had a bi-directional causal effect on PBC (Forward: OR: 0.37, 95% CI:0.15-0.93; Reverse: OR: 1.03, 95% CI:1.00-1.05)., Conclusion: We found a new potential causal effect between cirrhosis and intestinal flora and provided new insights into the role of gut microbiota in the pathological progression of liver cirrhosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Xiao, Yang, Chen, Xie, Li, Fu, Han, Qin, Tian, Zhao, Cai, Hu, Ai, Li, Chen, Wang, Tan, Xia and Zhang.)

Male infertility is a global concern, with a noticeable increase in the decline of spermatogenesis and sperm quality. However, there are limited clinically effective treatments available. This study aimed to investigate the potential effectiveness of puerarin in treating male infertility, which leads to gonadal changes. The results obtained from various analyses such as CASA, immunofluorescence, DIFF-Quick, hematoxylin and eosin (H&E), and periodic acid-Schiff (PAS) staining demonstrated that puerarin supplementation significantly alleviated the busulfan-induced reduction in spermatogenesis and sperm quality in both young and adult mice. Furthermore, puerarin exhibited a marked improvement in the damage caused by busulfan to the architecture of seminiferous tubules, causal epididymis, blood-testicular barrier (BTB), as well as spermatogonia and Sertoli cells. Similarly, puerarin significantly reduced the levels of total antioxidant capacity (T-AOC), malondialdehyde (MDA), and caspase-3 in the testes of busulfan-induced mice, as determined by microplate reader analysis. Additionally, RNA-seq data, RT-qPCR, and western blotting revealed that puerarin restored the abnormal gene expressions induced by busulfan to nearly healthy levels. Notably, puerarin significantly reversed the impact of busulfan on the expression of marker genes involved in spermatogenesis and oxidative stress. Moreover, puerarin suppressed the phosphorylation of p38, ERK1/2, and JNK in the testes, as observed through testicular analysis. Consequently, this study concludes that puerarin may serve as a potential alternative for treating busulfan-induced damage to male fertility by inactivating the testicular MAPK pathways. These findings may pave the way for the use of puerarin in addressing chemotherapy- or other factors-induced male infertility in humans., Competing Interests: Declaration of Competing Interest The authors declare that they have NO affiliations with or involvement in any organization or entity with any financial interest in the subject matter or materials discussed in this manuscript., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objective: Cognitive impairment, one of the most prevalent complications of trigeminal neuralgia, is troubling for patients and clinicians due to limited therapeutic options. Curcumin shows antinociception and neuroprotection pharmacologically, suggesting that it may have therapeutic effect on this complication. This study aimed to investigate whether curcumin alleviates orofacial allodynia and improves cognitive impairment by regulating hippocampal CA1 region synaptic plasticity in trigeminal neuralgia., Methods: A mouse model of trigeminal neuralgia was established by partially transecting the infraorbital nerve (pT-ION). Curcumin was administered by gavage twice daily for 14 days. Nociceptive thresholds were measured using the von Frey and acetone test, and the cognitive functions were evaluated using the Morris water maze test. Dendritic spines and synaptic ultrastructures in the hippocampal CA1 area were observed by Golgi staining and transmission electron microscopy., Results: Curcumin intervention increased the mechanical and cold pain thresholds of models. It decreased the escape latency and distance to the platform and increased the number of platform crossings and dwell time in the target quadrant of models, and improved spatial learning and memory deficits. Furthermore, it partially restored the disorder of the density and proportion of dendritic spines and the abnormal density and structure of synapses in the hippocampal CA1 region of models., Conclusion: Curcumin alleviates abnormal orofacial pain and cognitive impairment in pT-ION mice by a mechanism that may be related to the synaptic plasticity of hippocampal CA1, suggesting that curcumin is a potential strategy for repairing cognitive dysfunction under long-term neuropathic pain conditions.

Discriminating between Higgs production mechanisms can play a crucial role in determining the couplings of Higgs to gauge bosons, probing the nature of electroweak symmetry breaking. We propose a novel method to distinguish the Higgs production mechanisms at the LHC by utilizing the jet charge asymmetry of the two leading forward jets in Higgs plus two jets production. This novel observable provides a way to disentangle the W fusion from the Z fusion and gluon fusion processes for the first time, due to the electric charge correlation of the two leading jets in the events. We show that the Higgs couplings to gauge bosons can be well constrained, and its conclusion does not depend on the other possible new physics effects which modify the Higgs total or partial width. We also discuss the complementary roles between the proposed jet charge asymmetry measurement and the Higgs signal strength measurements at the high luminosity LHC (HL-LHC) in determining the Higgs couplings.

Ammonia production via glutamate dehydrogenase is inhibited by SIRT4, a sirtuin that displays both amidase and non-amidase activities. The processes underlying the regulation of ammonia removal by amino acids remain unclear. Here, we report that SIRT4 acts as a decarbamylase that responds to amino acid sufficiency and regulates ammonia removal. Amino acids promote lysine 307 carbamylation (OTC CP-K307 ) of ornithine transcarbamylase (OTC), which activates OTC and the urea cycle. Proteomic and interactome screening identified OTC as a substrate of SIRT4. SIRT4 decarbamylates OTC CP-K307 and inactivates OTC in an NAD + -dependent manner. SIRT4 expression was transcriptionally upregulated by the amino acid insufficiency-activated GCN2-eIF2α-ATF4 axis. SIRT4 knockout in cultured cells caused higher OTC CP-K307 levels, activated OTC, elevated urea cycle intermediates and urea production via amino acid catabolism. Sirt4 ablation decreased male mouse blood ammonia levels and ameliorated CCl 4 -induced hepatic encephalopathy phenotypes. We reveal that SIRT4 safeguards cellular ammonia toxicity during amino acid catabolism., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Lifespan longevity has attracted increasing attention with societal development. To counter the effects of aging on longevity, we focused on the natural chemicals of plants. In this study, we investigated the effects of puerarin supplementation on the lifespan of Drosophila melanogaster . Puerarin supplementation significantly extended the lifespan of D. melanogaster at 60 μM and 120 μM by upregulating proteasome subunit beta 5 (prosbeta5) and sirtuin-1 (Sirt1). However, puerarin-induced longevity of male flies (F0 generation) may not be passed on to descendants. Additionally, a puerarin diet for 10 and 25 days did not influence the body weight and food intake of male Canton-S flies. Puerarin significantly improved the climbing ability, starvation resistance, and oxidation resistance of male flies by upregulating the expression of Shaker, catalase (CAT), superoxide dismutase 1 (SOD1), and Methuselah, and downregulating poly [ADP-ribose] polymerase (PARP-1) and major heat shock 70 kDa protein Aa (HSP70). Moreover, 120 μM puerarin supplementation for 25 days significantly increased adenosine 5' triphosphate (ATP) content by increasing adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) levels. Additionally, the puerarin diet for 25 days suppressed male fecundity in male flies by decreasing the levels of Bam and Punt. Mechanistically, puerarin enhanced lysosome-involved autophagy by promoting the expression of lysosome markers [β-galactosidase and lysosomal associated membrane protein 1 (LAMP1)], and elevating the levels of autophagy-related genes, including autophagy-associated gene 1 (ATG1), ATG5, and ATG8b. However, puerarin decreased the phosphorylation of the target of rapamycin (TOR) protein. In conclusion, puerarin is a promising compound for improving the longevity of D. melanogaster by activating autophagy.

Background: Colonoscopy is the main kind of way to detect and treat diseases about large intestine, but during the examination and preparation, these 2 processes are able to lead abdominal pain, abdominal distention and other discomfort feel, which will cause patients to refuse the examination and become anxious. Painless and sedative endoscopy may reduce discomfort of patients, but there is a risk of adverse effects. Many studies have shown that playing music during colonoscopy can reduce discomfort and increase acceptance of colonoscopy, but the conclusion remains controversial. The 3 approaches of random, single-blind, controlled method were used to investigate the interventions effects of piano light music on satisfaction, anxiety and pain in patients undergoing colonoscopy., Methods: A total of 216 patients were randomly divided into piano music group (n = 112, piano music played during colonoscopy) and control group (n = 104, no music during colonoscopy) to compare patients satisfaction, anxiety score, pain score, vital signs, endoscopic difficulty score, and willingness to undergo colonoscopy again., Results: There were no significant differences in vital signs, pre-colonoscopic state anxiety score, and trait anxiety score before and after colonoscopy, and willingness to undergo colonoscopy again between the 2 groups (P > .05). The difficulty of colonoscopy operation and the score of state anxiety after colonoscopy in the piano group were lower than those in the control group (P < .05), and the satisfaction of colonoscopy process, pain management and overall service satisfaction were better than those of the control group (P < .05), and they were more likely to listen to music in the next examination (P < .001)., Conclusion: The light music played by piano can relieve patients' anxiety, improve the satisfaction of colonoscopy process, pain management and service satisfaction, reduce the difficulty of colonoscopy, which have no obvious adverse reactions. Therefore, it is worthy of promotion., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Rationale: Familial adenomatous polyposis (FAP) is an autosomal dominant genetic disease, with a very high cancer rate. At present, endoscopic resection of polyps ≥ 1 cm is often chosen for patients with non-cancerous polyps who are unwilling to undergo surgery, and regular review is conducted. Once the polyps are pathologically confirmed to be cancerous, surgical resection of the diseased large intestine is generally recommended, but surgery often leads to a series of complications. So what do you do with cancer patients who don't want surgery?, Patient Concerns: A 19-year-old woman presented with intermittent hematochezia with abdominal pain. A colonoscopy revealed hundreds of intestinal polyps., Diagnoses: The patient had a family history of FAP, and there were hundreds of polyps in the intestine. The pathology was adenomatous, and some polyps became cancerous, which met the diagnostic criteria of FAP., Interventions: Endoscopic examination was arranged for the patient, the resection of intestinal polyps ≥ 1 cm was given priority, and other polyps were removed as far as possible. After that, metformin 500 mg orally was given twice a day, and endoscopic follow-up was conducted every 6 months. During each endoscopic follow-up, intestinal polyps ≥ 1 cm were preferred to be removed, and other polyps were removed as far as possible., Outcomes: The patient's abdominal pain and blood in the stool disappeared after endoscopic treatment. Cancerous polyps were found at the second and third follow-up visits, but the patient always refused surgical treatment. After 4 years of follow-up, polyp load was significantly reduced, abdominal pain and bloody stool symptoms did not appear again, and imaging examination showed no tumor recurrence and metastasis., Lessons: Endoscopic polyp resection is an important method to treat the clinical symptoms of FAP. Metformin combined with endoscopic therapy is a good alternative for patients with familial polyposis who do not want surgery. When the polyp is cancerous and the polyp is radically resected by the endoscope, if the patient refuses additional surgery, oral metformin combined with endoscopic follow-up can be considered., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: Trigeminal neuralgia (TN), one of the most severe and debilitating chronic pain conditions, is often accompanied by mood disorders, such as anxiety and depression. Electroacupuncture (EA) is a characteristic therapy of Traditional Chinese Medicine with analgesic and anxiolytic effects. This study aimed to investigate whether EA ameliorates abnormal TN orofacial pain and anxiety-like behavior by altering synaptic plasticity in the hippocampus CA1., Materials and Methods: A mouse infraorbital nerve transection model (pT-ION) of neuropathic pain was established, and EA or sham EA was used to treat ipsilateral acupuncture points (GV20-Baihui and ST7-Xiaguan). Golgi-Cox staining and transmission electron microscopy (TEM) were administrated to observe the changes of synaptic plasticity in the hippocampus CA1., Results: Stable and persistent orofacial allodynia and anxiety-like behaviors induced by pT-ION were related to changes in hippocampal synaptic plasticity. Golgi stainings showed a decrease in the density of dendritic spines, especially mushroom-type dendritic spines, in hippocampal CA1 neurons of pT-ION mice. TEM results showed that the density of synapses, membrane thickness of the postsynaptic density, and length of the synaptic active zone were decreased, whereas the width of the synaptic cleft was increased in pT-ION mice. EA attenuated pT-ION-induced orofacial allodynia and anxiety-like behaviors and effectively reversed the abnormal changes in dendritic spines and synapse of the hippocampal CA1 region., Conclusion: EA modulates synaptic plasticity of hippocampal CA1 neurons, thereby reducing abnormal orofacial pain and anxiety-like behavior. This provides evidence for a TN treatment strategy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Jia, Li, Zhang, Wu, Zhang, Zhi, Wang, Zhu, Wang, Xu, Tian and Cui.)

Multi-isotope systems have shown great application potential in tracing geological and environmental processes. In order to obtain the isotopic composition of multiple elements of interest, the common protocol is to separate each element from the matrix by independent procedures, which has some limitations, including poor efficiency, being time-consuming, requiring large samples and being unsuitable for rare samples ( e.g. , meteorite, lunar soil and atmospheric aerosol samples). In this study, we present an integrated and optimized one-step method to separate Cu, Fe, Zn and Cd from complex matrix elements using the AG MP-1M anion exchange resin. By experimentally optimizing the resin volume, eluent concentration and eluent amount, these target elements can be effectively separated from the matrix elements, such as Cu separation from Ti and Co, Zn separation from Fe and Cd, and Cd separation from Sn. The recoveries of Cu, Fe, Zn and Cd were 100.1 ± 0.8% (2SD, n = 3), 99.8 ± 0.7% (2SD, n = 3), 100 ± 0.8% (2SD, n = 3) and 99 ± 1% (2SD, n = 3), respectively. Moreover, the resolution ( R ) between the elements of interest and interfering elements was in the range of 1.8-28.1. The process blanks of Cu, Fe, Zn and Cd were 1-1.6 ng, 62-70 ng, 2.1-3 ng and 66-74 pg, respectively. The obtained isotope ratios for the standard reference materials agreed well with the published values. Meanwhile, we have reported the Cu, Fe and Zn isotope ratios of six soil and sediment standard reference materials, namely NIST 2711a, GSS-1, GSD-5a, GSD-7a, GSD-12 and GSD-23, for the first time. These new data can be used for the intercalibration and quality control of soils and sediments in other laboratories. The one-step separation of Cu, Fe, Zn and Cd shows obvious economic and efficiency advantages, making it suitable for the simultaneous separation of multiple elements of interest in geological samples.

Bacillus thuringiensis , a gram-positive bacteria, has three insecticidal proteins: Vip (vegetative insecticidal protein), Cry (crystal), and Sip (secreted insecticidal protein). Of the three, Sip proteins have insecticidal activity against larvae of Coleoptera. However, the Sip1Aa protein has little solubility in the supernatant because of inclusion bodies. This makes it more difficult to study, and thus research on Sip proteins is limited, which hinders the study of their mechanistic functions and insecticidal mechanisms. This highlights the importance of further investigation of the Sip1Aa protein. Disulfide bonds play an important role in the stability and function of proteins. Here, we successfully constructed mutant proteins with high insecticidal activity. The tertiary structure of the Sip1Aa protein was analyzed with homologous modeling and bioinformatics to predict the conserved domain of the protein. Cysteine was used to replace amino acids via site-directed mutagenesis. We successfully constructed Sip149-251, Sip153-248, Sip158-243, and Sip178-314 mutant proteins with higher solubility than Sip1Aa. Sip153-248 and Sip158-243 were the most stable compared to Sip1Aa, followed by Sip149-251 and Sip178-314. The insecticidal activity of Sip153-248 (Sip158-243) was 2.76 (2.26) times higher than that of Sip1Aa. The insecticidal activity of Sip149-251 and Sip178-314 did not differ significantly from that of Sip1Aa. Basic structural properties, physicochemical properties, and the spatial structure of the mutation site of Sip1Aa and the mutant proteins were analyzed. These results provide a molecular basis for using Sip1Aa to control Coleopteran insects and contribute to the study of the Sip1Aa insecticidal mechanism., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Ding, Wang, Gao, Liu and Li.)

Objective: To investigate the effect of PPP2R5C to the activity of Molt-4 cells in childhood acute T lymphocytic leukemia and its mechanism., Methods: The small interfering RNA (siRNA) technology targeting PPP2R5C gene was used to down-regulate the expression of PPP2R5C in Molt-4 cells. At the same time, a blank control group, a negative control group and a 17-DMAG group were set up. The cells in the negative control group were transfected with siRNA-NC, the cells in 17-DMAG group were treated with the HSP90 inhibitor 17-DMAG at a final concentration of 6.4 μmol/L for 48 h. Real-time fluorescent quantitative PCR (RT-qPCR) and Western blot were used to detect transfection efficiency; CCK-8 method was used to detect the proliferation activity of the cells in each group, EdU was used to detect the proliferation level of the cells in each group, flow cytometry was used to detect the cell cycle distribution ratio of the cells in each group, Annexin V-FITC/PI staining was used to detect the apoptosis of the cell, RT-qPCR and Western blot were used to detect the expression changes of heat shock protein 90 (HSP90) and glucocorticoid receptor (GR) of the cells in each group., Results: After Molt-4 cells were transfected with siRNA-PPP2R5C, the expression of PPP2R5C mRNA and protein in the cells were down-regulated significantly compared with those in the blank control group and the si-NC group (P<0.05); compared with cells in the blank control group and the si-NC group, the proliferation activity of the cells in the siRNA-PPP2R5C group and the 17-DMAG group significantly decreased (P<0.05), and the rate of EdU positive cells was significantly reduced (P<0.05); the proportion of the cells in G1 phase decreased while the proportion of the cells in G 2 phase increased (P<0.05), the apoptosis rate of the cells also increased significantly (P<0.05); in addition, the expression of PPP2R5C mRNA and protein of the cells in siRNA-PPP2R5C group was significantly down-regulated compared with those in the blank control group and si-NC group (P<0.05). The expressions of PPP2R5C mRNA and protein in the 17-DMAG group were also significantly down-regulated compared with those in the blank control group and si-NC group (P<0.05)., Conclusion: Down-regulation of PPP2R5C gene expression can inhibit Molt-4 cell activity in childhood acute T lymphocytic leukemia, block the cells in G 2 phase, and promote cell apoptosis, the mechanism may be related to the inhibition of HSP90-GR signaling pathway.

BACKGROUND This study aimed to investigate frontoparietal network (FPN) dysfunction in participants with migraine without aura (MwoA). MATERIAL AND METHODS We selected 48 age-, sex-, and education level-matched graduate students (24 participants with MwoA [MwoA group] and 24 healthy controls). RS-fMRI and independent component analysis were used to examine the FPN and to compare abnormal encephalic regional homogeneity values. The Mindful Attention Awareness Scale (MAAS), Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS), and Self-Rating Scale of Sleep (SRSS) were used to evaluate attention, anxiety, depression, and sleep, respectively. Pearson's correlation was applied to evaluate the association between abnormal brain areas and the scores for each scale. RESULTS Neural function activity in encephalic regions of FPN showed abnormal changes in the MwoA group. The MwoA group had significantly lower MAAS scores (P<0.001), higher SAS scores (P<0.001), and higher SDS (P=0.06) and SRSS scores (P=0.26). In the MwoA group, functional activity of the right parietal lobule in the left FPN was positively correlated with MAAS scores (P=0.01) and negatively correlated with SAS (P=0.02). The orbital part of left inferior frontal gyrus activity in the right FPN was positively correlated with SDS (P=0.04) and SRSS (P<0.001). Right superior marginal gyrus activity in the right FPN was positively correlated with SDS (P=0.02). CONCLUSIONS Abnormal FPN function was correlated with attention, anxiety, depression, and sleep status in the MwoA group. These results offer further insights into the evaluation and treatment of MwoA.

Drug resistance is a critical factor responsible for the recurrence of non-small cell lung cancer (NSCLC). Previous studies suggest that curcumin acts as a chemosensitizer and radiosensitizer in human malignancies, but the underlying mechanism remains elusive. In the present study, we explored how curcumin regulates the expression of miR-142-5p and sensitizes NSCLC cells to crizotinib. We found that miR-142-5p is significantly downregulated in NSCLC tissue samples and cell lines. Curcumin could increase crizotinib cytotoxicity by epigenetically restoring the expression of miR-142-5p. Furthermore, curcumin treatment suppressed the expression of DNA methylation-related enzymes, including DNMT1, DNMT3A, and DNMT3B, in NSCLC cells. In addition, the upregulation of miR-142-5p expression increased crizotinib cytotoxicity and induced apoptosis in tumor cells in a similar manner to that of curcumin. Strikingly, miR-142-5p overexpression suppressed crizotinib-induced autophagy in A549 and H460 cells. Mechanistically, miR-142-5p inhibited autophagy in lung cancer cells by targeting Ulk1. Overexpression of Ulk1 abrogated the miR-142-5p-induced elevation of crizotinib cytotoxicity in A549 and H460 cells. Collectively, our findings demonstrate that curcumin sensitizes NSCLC cells to crizotinib by inactivating autophagy through the regulation of miR-142-5p and its target Ulk1.

Rationale: Respiratory distress syndrome (RDS) refers to the symptoms of progressive dyspnea and respiratory failure in newborns shortly after birth. The clinical and genetic characteristics of patients with neonatal RDS have not been extensively reported., Patient Concerns: A infant was in critical condition with repeated paroxysmal blood oxygen decline. Oxygen inhalation and noninvasive ventilator-assisted breathing relief were not effective. The etiology was unclear, and there was no family history of lung disease. Surface-active substance replacement therapy and positive pressure-assisted ventilation support were ineffective., Diagnosis: The infant was clinically diagnosed with RDS. Genetic tests revealed a heterozygous missense mutation in the c.168 surfactant protein C (SFTPC) gene., Interventions: Tracheal intubation was performed with invasive ventilator-assisted breathing, pulmonary surfactant was administered. Supportive treatment for liver protection and administration of a cardiotonic diuretic, vasodilator, human immunoglobulin (intravenous infusion), fresh frozen plasma, and suspended red blood cells were performed., Outcomes: The infant showed poor responses to respiratory and circulatory support, antibiotic treatment, and other treatment methods. The patient was discharged from hospital against the advice of us, cut off from us. The long-term prognosis of the patient after discharge remains unknown., Lessons: SFTPC gene mutations may be an important risk factor for the development of common lung diseases. Because of the important roles of surfactant functions and metabolism, mutations in these genes can affect the production and function of pulmonary surfactant, leading to severe lung disease in term newborns., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Foodborne pathogens can cause illnesses. Existing tools for detecting foodborne pathogens are typically time-consuming or require complex protocols. Here, we report an assay to directly analyze pathogenic genes based on CRISPR-Cas12. This new test, termed proximal DNA probe-based CRISPR-Cas12 (PPCas12), facilitates the detection of foodborne pathogens without amplification steps. The elimination of the nucleic acid amplification process dramatically reduced the processing time, complexity, and costs in the analysis of foodborne pathogens. The substitution of the frequently used dually labeled DNA reporter with a proximal DNA probe in the PPCas12 assay led to a 4-fold sensitivity enhancement. PPCas12 offered a limit of detection of 619 colony-forming units in the detection of Salmonella enterica ( S. enterica ) without the nucleic acid amplification process. The specific recognition of genes via PPCas12 allowed distinguishing S. enterica from other foodborne pathogens. The PPCas12 assay was applied in the screening of S. enterica contamination on fresh eggs with high precision. Hence, the new PPCas12 assay will be a valuable tool for on-site monitoring of foodborne pathogens.

Professor ZHENG Liang believes that the main pathogenesis of postoperative facial paralysis is related to the retarded circulation of qi and blood and malnutrition of tendons and vessels in local area because of local retention of "stasis" after surgical trauma. In treatment of postoperative facial paralysis with acupotomy, the abnormal facial structure after operation should be considered specially. The region where acupotomy is exerted is determined by taking surgical scar as the center so that the local adhesion can be released and separated. In treatment, the knife needle should be as fine as possible and the attention be paid to the direction of needle insertion and the release amplitude. The frequency of acupotomy should be once per week.

Jet production and jet substructure in reactions with nuclei at future electron-ion colliders will play a preeminent role in the exploration of nuclear structure and the evolution of parton showers in strongly interacting matter. In the framework of soft-collinear effective theory, generalized to include in-medium interactions, we present the first theoretical study of inclusive jet cross sections and the jet charge at the electron-ion collider. Predictions for the modification of these observables in electron-gold relative to electron-proton collisions reveal how the flexible center-of-mass energies and kinematic coverage at this new facility can be used to enhance the signal and maximize the impact of the electron-nucleus program. Importantly, we demonstrate theoretically how to disentangle the effects from nuclear parton distribution functions and the ones that arise from strong final-state interactions between the jet and the nuclear medium.

Transcriptome-wide association studies (TWAS) have identified several genes that are associated with qualitative traits. In this work, we performed TWAS using quantitative traits and predicted gene expressions in six brain subcortical structures in 286 mild cognitive impairment (MCI) samples from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. The six brain subcortical structures were in the limbic region, basal ganglia region, and cerebellum region. We identified 9, 15, and 6 genes that were stably correlated longitudinally with quantitative traits in these three regions, of which 3, 8, and 6 genes have not been reported in previous Alzheimer's disease (AD) or MCI studies. These genes are potential drug targets for the treatment of early-stage AD. Single-Nucleotide Polymorphism (SNP) analysis results indicated that cis-expression Quantitative Trait Loci (cis-eQTL) SNPs with gene expression predictive abilities may affect the expression of their corresponding genes by specific binding to transcription factors or by modulating promoter and enhancer activities. Further, baseline structure volumes and cis-eQTL SNPs from correlated genes in each region were used to predict the conversion risk of MCI patients. Our results showed that limbic volumes and cis-eQTL SNPs of correlated genes in the limbic region have effective predictive abilities.

Alzheimer's disease (AD) is a neurodegenerative brain disease in the elderly. Identifying patients with mild cognitive impairment (MCI) who are more likely to progress to AD is a key step in AD prevention. Recent studies have shown that AD is a heterogeneous disease. In this study, we propose a subtyping-based prediction strategy to predict the conversion from MCI to AD in three years according to MCI patient subtypes. Structural magnetic resonance imaging (sMRI) data and multi-omics data, including genotype data and gene expression profiling derived from peripheral blood samples, from 125 MCI patients were used in the Alzheimer's Disease Neuroimaging Initiative (ADNI)-1 dataset and from 98 MCI patients in the ADNI-GO/2 dataset. A variational Bayes approximation model based on the multiple kernel learning method was constructed to predict whether an MCI patient will progress to AD within three years. In internal fivefold cross-validation within ADNI-1, we achieved an overall AUC of 0.83 (79.20% accuracy, 81.25% sensitivity, 77.92% specificity) compared to the model without subtyping, which achieved an AUC of 0.78 (76.00% accuracy, 77.08% sensitivity, 75.32% specificity). In external validation using ADNI-1 as a training set and ADNI-GO/2 as an independent test set, we attained an AUC of 0.78 (74.49% accuracy, 74.19% sensitivity, 74.63% specificity). Identifying MCI patient subtypes with omics data would improve the accuracy of predicting the conversion from MCI to AD. In addition to evaluating statistics, obtaining the significant sMRI, single nucleotide polymorphism (SNP) and mRNA expression data from peripheral blood of MCI patients is noninvasive and cost-effective for predicting conversion from MCI to AD.

Prometryne is a widely used herbicide in China to control annual grasses and broadleaf weeds. However, the stability of prometryne makes it difficult to be degraded, which poses a threat to human health. This study presents a bacterial strain isolated from soil samples with a prometryne application history, designated strain DY-1. Strain DY-1, identified as Pseudomonas sp., is capable of utilizing prometryne as a sole carbon source for growth and degrading 100% of prometryne within 48 h from an initial concentration of 50 mg L -1 . To further optimize the degradation of prometryne, the prometryne concentration, temperature, pH, and salt concentration were examined. The optimal conditions for degradation of prometryne by strain DY-1 were an initial prometryne concentration of 50 mg L -1 , 30 °C, pH 7-8, and NaCl concentration of 200 mg L -1 . The same strain also degraded other s-triazine herbicides, including simetryne, ametryne, desmetryne, and metribuzin, under the same conditions. The biodegradation pathway of prometryne was established by isolating sulfoxide prometryne as the first metabolite and by the identification of sulfone prometryne and 2-hydroxy prometryne by liquid chromatography-mass spectrometry (LC-MS/MS). The results illustrated that strain DY-1 achieved the removal of prometryne by gradually oxidizing and hydrolyzing the methylthio groups. A bioremediation trial with contaminated soil and pot experiments showed that after treating the prometryne-contaminated soil with strain DY-1, the content of prometryne was significantly reduced (P < 0.05). This study provides an efficient bacterial strain and approach that could be potentially useful for detoxification and bioremediation of prometryne analogs.

Resina Draconis, a rare and precious traditional medicine in China, is known as the &quot;holy medicine for promoting blood circulation&quot;. According to the national drug standard, it's derived from the resin extracted from the wood of Dracaena cochinchinensis, a Liliaceae plant. In addition, a variety of Dracaena species all over the world can form red resins, and there is currently no molecular identification method that can efficiently identify the origin of Dracaena medicinal materials. In this study, seven species of Dracaena distributed in China were selected as the research objects. Four commonly used DNA barcodes(ITS2, matK, rbcL and psbA-trnH), and four highly variable regions(trnP-psaJ, psbK-psbI, trnT-trnL, clpP) in chloroplast genome were used to evaluate the identification efficiency of Dracaena species. The results showed that clpP sequence fragment could accurately identify seven species of Dracaena plants. However, due to the long sequence of clpP fragment, there were potential problems in the practical application process. We found that the combined fragment &quot;psbK-psbI+ trnP-psaJ&quot; can also be used for accurate molecular identification of the Resina Draconis origin plants and relative species of Dracaena, which were both relatively short sequences in the combined fragment, showing high success rates of amplification and sequencing. Therefore, the &quot;psbK-psbI+ trnP-psaJ&quot; combined fragment can be used as the DNA barcode fragments for molecular identification of Resina Dracon's origin plants and relative species of Dracaena. Research on the identification of Dracaena species, the results of this study can be used to accurately identify the original material of Resina Draconis, and providing effective means for identification, rational development and application of Resina Draconis base source.

Ethnopharmacological Relevance: As a traditional Chinese medicine, Taraxacum mongolicum has been widely used for the prevention and treatment of a variety of inflammatory and infectious diseases, and also clinically used as a remedy for mastitis. However, the scientific rationale and mechanism behind its use on mastitis in vivo are still unclear., Aim of the Study: This study aimed to investigate the protective effect and potential mechanism of Taraxacum mongolicum Hand.-Mazz. (T. mongolicum) on mastitis infected by Staphylococcus aureus (S. aureus)., Materials and Methods: Female ICR mice were given intragastrically 2.5, 5 and 10 g/kg of T. mongolicum extract twice per day for 6 consecutive days, and infected with S. aureus via teat canal to induce mastitis. Pro-inflammatory cytokine tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) levels were determined by ELISA. Myeloperoxidase (MPO) activity and distribution were measured by reagent kit and immunohistochemistry. Histopathological changes of mammary gland tissues were observed by H&E staining. Toll-like receptor 2 (TLR2) expression, phosphorylations of related proteins in nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs) signaling pathways were detected by western blot., Results: T. mongolicum decreased TNF-α, IL-6 and IL-1β levels, and reduced MPO activity and distribution in sera and mammary glands with S. aureus-infected mastitis. In addition, T. mongolicum effectively attenuated histopathological damages and cell necrosis of mammary gland tissues infected by S. aureus. Moreover, T. mongolicum inhibited the expression of TLR2, and the phosphorylations of inhibitor κBα (IκBα), p65, p38, extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK) proteins in mammary glands with S. aureus-infected mastitis., Conclusions: This study suggests that T. mongolicum protects against S. aureus-infected mastitis by exerting anti-inflammatory role, which is attributed to the inhibition of TLR2-NF-κB/MAPKs pathways., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Aspidopterys obcordata var. obcordata, a medicinal plant endemic to China, is a narrowly distributed species and wild resources are extremely limited. To evaluate the genetic variability and degree of genetic divergence of A. obcordata var. obcordata, and to make rational scientific decisions on its harvest and germplasm conservation, we collected 122 samples from across nearly all of its distribution area and studied genetic diversity using inter-simple sequence repeats (ISSRs), sequence-related amplified polymorphisms (SRAPs), and a method combining the two techniques. The results revealed the high genetic diversity of A. obcordata var. obcordata, mainly due to its intra-population diversity, and the top two populations with the highest levels of intra-population diversity were ML and DH, individuals of which can serve as excellent germplasm candidates during the processing of germplasm screening and conservation. In general, the combining method was prior to the ISSR analyses and SRAP analyses results, except for a slight difference in the genetic structure of individual populations. Therefore, we suggest that a combination analysis of the two marker methods is ideal for evaluating the genetic diversity and genetic relationships of A. obcordata var. obcordata.

Purpose: To investigate the effect of vascularized free fibular flap in repairing segmental mandibular defects., Methods: Eighty patients with segmental mandibular defects treated in our hospital from June 2015 to May 2018 were enrolled. Both groups of patients were operated by the same group of medical staff with more than 5 years of clinical experience. Patients were divided into 2 groups using a random number table method, 40 in each group. Patients in the control group underwent non-vascularized iliac bone graft while patients in the experimental, group underwent vascularized free fibular bone flap repair. The graft survival, pain, quality of life, negative emotions and complications were compared between the two groups using SPSS 22.0 software package., Results: There was no significant difference in the scores of the proximal gingival papilla, distal gingival papilla, labial margin and labial margin (P>0.05). The gingival texture, color score and total score of the root surface of the experimental group were significantly higher than the control group (P<0.05). The scores of VAS, anxiety and depression in both groups were significantly decreased after operation, but the decrease in the experimental group was greater(P<0.05). Physical function, psychological and social function, life quality of the two groups were significantly increased, but the increase of the experimental group was greater (P<0.05).Three cases (7.5%) developed complications in the control group, including 1 case of pneumonia, 1 case of infection and 1 case of wound recurrence. Two cases(5%) in the experimental group developed of complications, including 1 case of wound recurrence and 1 case of pneumonia, the difference was not statistically significant (P>0.05)., Conclusions: Repair of mandibular segmental defect with vascularized free fibular bone flap can significantly improve the overall effect, relieve pain and negative emotion, improve quality of life of patients and decrease incidence of complications.

The study aims at exploring the composition and characteristics of the medicinal plant resources of six major ethnic minorities living in Xishuangbanna, as well as the characteristics of traditional utilization of ethnic medicine, and promote the rational protection and inheritance and utilization of ethnic medicine resources and traditional knowledge. Based on the fourth survey of traditional Chinese medicine resources in Xishuangbanna, Yunnan province, through the methods of literature collection, interviewing and field investigation, this paper analyzed the data of the types, medicinal parts and attending diseases of medicinal plant resources of Dai, Hani, Jinuo, Wa, Lahu and Bulang nationalities. The results showed that there were 1 048 medicinal plant resources of the six ethnic minorities, and the medicinal plants were 735, 497, 272, 295, 280 and 49 in the six nationalities, respectively. The cross-use of medicinal plants among the six nationalities accounted for 62.45%, 78.07%, 88.60%, 87.46%, 82.25% and 95.92%, respectively. The main medicinal plants used by the six major ethnic minorities are root and rhizome, whole grass, leaf and stem. Various ethnic medicinal plants are mainly used in the treatment of diseases of digestive system, respiratory system, rheumatic disease, trauma, snake and insect bite and other external diseases. This study showed that Xishuangbanna has rich resources of ethnic medicinal plants. The ethnic medicine culture with Dai medicine as the main part has a long history and diversified theories, forming a unique ethnic characteristic culture. However, all ethnic medicine resources and the application of traditional knowledge are faced with the risk of gradually decreasing, it is suggested to strengthen the mining, Xishuangbanna folk medicine of ethnic culture protection and inheri-tance, and to develop regional economy and the international community has a positive influence.

Professor YANG Wen - hui 's clinical experience of treating alopecia areata with combination of acupuncture and Chinese herbs based on yingwei theory was summarized. Professor YANG divides alopecia areata into ying qi disease and wei qi disease. Alopecia areata belonging to wei qi disease locates on the skin and is related to the lung and kidney, and belonging to ying qi disease locates in the meridians and is related to the heart, spleen and stomach. Acupuncture is chosen when the disease locates in the skin and meridians. If both viscera and meridians suffered, acupuncture and Chinese herbs should be combined. As for the acupuncture, professor YANG used the method of harmonizing yingwei needling to treat alopecia areata, which includes regulating the origin of yingwei , regulating the deficiency and excess of yingwei and regulating the operation of local yingwei . As for the Chinese herbs, wei qi disease can be washed out by Chinese herbs of relieving exterior wind and activating meridians and collaterals. The ying qi disease can be washed out by Chinese herbs in mild condition, and long course of disease can be given Guizhi decoction as the base, add or subtract according to syndrome.

To ensure the safety of medications, it is vital to accurately authenticate species of the Apocynaceae family, which is rich in poisonous medicinal plants. We identified Apocynaceae species by using nuclear internal transcribed spacer 2 (ITS2) and psbA-trnH based on experimental data. The identification ability of ITS2 and psbA-trnH was assessed using specific genetic divergence, BLAST1, and neighbor-joining trees. For DNA barcoding, ITS2 and psbA-trnH regions of 122 plant samples of 31 species from 19 genera in the Apocynaceae family were amplified. The PCR amplification for ITS2 and psbA-trnH sequences was 100%. The sequencing success rates for ITS2 and psbA-trnH sequences were 81% and 61%, respectively. Additional data involved 53 sequences of the ITS2 region and 38 sequences of the psbA-trnH region were downloaded from GenBank. Moreover, the analysis showed that the inter-specific divergence of Apocynaceae species was greater than its intra-specific variations. The results indicated that, using the BLAST1 method, ITS2 showed a high identification efficiency of 97% and 100% of the samples at the species and genus levels, respectively, via BLAST1, and psbA-trnH successfully identified 95% and 100% of the samples at the species and genus levels, respectively. The barcode combination of ITS2/psbA-trnH successfully identified 98% and 100% of samples at the species and genus levels, respectively. Subsequently, the neighbor joining tree method also showed that barcode ITS2 and psbA-trnH could distinguish among the species within the Apocynaceae family. ITS2 is a core barcode and psbA-trnH is a supplementary barcode for identifying species in the Apocynaceae family. These results will help to improve DNA barcoding reference databases for herbal drugs and other herbal raw materials., (Copyright © 2020 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

Colaphellus bowringi Baly mainly damages cruciferous vegetables, leading to huge economic losses. The secretory insecticidal protein (Sip) of Bacillus thuringiensis (Bt) has high insecticidal activity against C. bowringi Baly. The tertiary structure of Sip1Aa protein was analyzed by homologous modeling and other bioinformatics methods to predict the conserved domain of Sip1Aa protein. Acidic and basic amino acids in the conserved domain were selected, and alanine was used to replace these amino acids by site-directed mutation. The difference between the insecticidal activities of mutant protein and Sip1Aa protein was analyzed. The insecticidal activities of H99A, K109A, K128A, and E130A against C. bowringi Baly were significantly increased, among which that of K128A was the most obviously changed, and the LC 50 value was decreased by about 10 times compared with that of Sip1Aa protein. The LC 50 value of mutant E130A was 0.286 μg/mL, which was about six times less than that of Sip1Aa. K128 and E130 were both in the β9-β10 loop. The toxicity of D290A, H242A, and H303A to C. bowringi Baly was significantly reduced, and their LC 50 value increased by about six, eight, and three times compared with that of Sip1Aa protein, respectively. This study showed that acidic and basic amino acid residues played a certain role in the toxicity of Sip1Aa protein, and the loss of side chains in key residues had a significant impact on the insecticidal activity of the protein. This study provides the theoretical basis for revealing the relationship between the structure and function of Sip1Aa protein and also provides a new method for the subsequent study of sip gene., (Copyright © 2020 Wang, Ding, Wang, Liu, Li and Gao.)

In December 2019, an outbreak of viral pneumonia began in Wuhan, Hubei Province, which caused the spread of infectious pneumonia to a certain extent in China and neighboring countries and regions, and triggered the epidemic crisis. The coronavirus disease 2019(COVID-19) is an acute respiratory infectious disease listed as a B infectious disease, which is managed according to standards for A infectious disease. Traditional Chinese medicine and integrated traditional Chinese and Western medicine have played an active role in the prevention and control of this epidemic. China's ethnomedicine has recognized infectious diseases since ancient times, and formed a medical system including theory, therapies, formula and herbal medicines for such diseases. Since the outbreak of the COVID-19 epidemic, Tibet Autonomous Region, Qinghai Province, Inner Mongolia Autonomous Region, Xinjiang Uygur Autonomous Region and Chuxiong Autonomous Prefecture of Yunnan, Qiandongnan Autonomous Prefecture of Guizhou have issued the prevention and control programs for COVID-19 using Tibetan, Mongolian, Uygur, Yi and Miao medicines. These programs reflect the wisdom of ethnomedicine in preventing and treating diseases, which have successfully extracted prescriptions and preventive measures for the outbreak of the epidemic from their own medical theories and traditional experiences. In this paper, we summarized and explained the prescriptions and medicinal materials of ethnomedicine in these programs, and the origin of Tibetan medicine prescriptions and Mongolian medicine prescriptions in ancient books were studied. These become the common characteristics of medical prevention and treatment programs for ethnomedicine to formulate therapeutic programs under the guidance of traditional medicine theories, recommend prescriptions and prevention and treatment methods with characteristics of ethnomedicine, and focus on the conve-nience and standardization. However, strengthening the support of science and technology and the popularization to the public, and improving the participation of ethnomedicine in national public health services and the capacity-building to deal with sudden and critical diseases are key contents in the development of ethnomedicine in the future.

The role of genomic variation in differentiation is currently not well understood. Here, the genomic variations were determined with the whole-genome sequencing for three pairs of pluripotent stem cell lines and their corresponding BMP4-induced trophoblast cell lines. We identified ∼3,500 single nucleotide variations and ∼4,500 indels by comparing the genome sequenced data between the stem cell lines and the matched BMP4-induced trophoblast cell lines and annotated them by integrating the epigenomic and transcriptomic datasets. Relatively, introns enrich more variations. We found ∼45% (42 genes) of the differentially expressed genes in trophoblasts that associate genomic variations. Six variations, located at transcription factor binding sites where H3K4me3 and H3K27ac are enriched in both H1 and H1&#95;BMP4, were identified. The epigenetic status around the genomic variations in H1 was similar to that in H1&#95;BMP4. This means that the variation-associated gene's expression change can not be attributed to epigenetic alteration. The genes associated with the six variations were upregulated in differentiation. We inferred that during the differentiation, an increased in the expression level of the MEF2C gene is due to a genomic variation in chromosomes 5: 88179358 A > G, which is at a binding site of TFs KLF16, NR2C2, and ZNF740 to MEF2C. Allele G shows a higher affinity to the TFs in the induced cells. The increased expression of MEF2C leads to an increased expression of TF MEF2C's target genes, subsequently affecting the differentiation. Although genomic variation should not be a dominant factor in differentiation, we believe that genomic variation could indeed play a role in the differentiation from stem cells into trophoblast., (Copyright © 2020 Li, Liu, Liu and Sun.)

Objective: To investigate whether use of single-foot centered and double-foot centered weight-bearing X-rays has an impact on the relevant indicators of hallux valgus., Methods: A total of 55 female patients from the Department of Ankle Surgery of Beijing Tongren Hospital with hallux valgus (110 feet) were collected from September to December 2015. The age of these patients ranged from 18 to 43 years, with an average age of 47.9 ± 8.5 years. All selected patients fit the diagnostic criteria of hallux valgus and had weight-bearing single foot centered and double foot centered radiographs taken. During the projection, all patients were instructed to stand on the X-ray box, with the knee joint straightened and legs perpendicular to the floor. The projection center of the single foot was directed at the lateral part of the scaphoid bone of the foot, while the projection center was directed at the position between the scaphoid bones of both feet for the double-foot shooting. The hallux valgus angle (HAV), the intermetatarsal angle between the first and second metatarsals (IMA), the intermetatarsal angle between the first and fifth metatarsals (IM1-5), and the metatarsal adduction angle (MAA) were measured and examined. The difference between these two shooting conditions was compared and analyzed., Results: The differences in X-ray measurement results (IMA, HAV, IM1-5, and MMA) between different measures for the same patient were not statistically significant. The values of HAV, IMA, IM1-5, and MAA are common indexes for evaluating hallux valgus. The average IMA was 15.9° for single-foot centered and 14.1° for double-foot centered X-rays. The average HAV was 30.2° for single-foot centered and 29.7° for double-foot centered X-rays. The average IM1-5 was 31.1° for single-foot centered and 29.7° for double-foot centered X-rays. The average of metatarsal adduction angle was 13.8° for single-foot centered and 14.1° for double-foot centered X-rays. The differences between single-foot centered and double-foot centered X-rays were statistically significant in terms of the measurement index (P < 0.05). In addition, compared with double-foot centered weight-bearing X-rays, the focus of single-foot centered X-rays was located on the lateral part of the scaphoid bone of the foot, and the ray was closer to the vertical foot in the single-foot centered weight-bearing X-ray., Conclusion: When the weight-bearing position and projection distance are the same, the single-foot centered weight-bearing X-ray is more effective in evaluating the severity of hallux valgus compared with the double-foot centered weight-bearing X-ray., (© 2019 The Authors. Orthopaedic Surgery published by Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.)

Myocardial dysfunction is an important manifestation of sepsis. In addition, inactivation of the mitogen-activated protein kinase (MAPK) signaling pathway has been reported to be beneficial in sepsis. The current study used gene expression profiling to demonstrate the overexpression of angiotensin II type 1 receptor (AT1R) and activation of the MAPK signaling pathway in sepsis. In this study, we used a rat model of sepsis established by cecal ligation and puncture to explore the mechanism of AT1R silencing in relation to the MAPK signaling pathway on myocardial injury. Various parameters including blood pressure, heart rate, and cardiac function changes were observed. Enzyme-linked immunosorbent assay was used to measure the concentration of cardiac troponin T (TnT), cardiac troponin I (cTnI), and creatine kinase isoenzyme muscle/brain (CK-MB). Myocardial enzyme, tissue antioxidant capacity, mitochondria swelling, and membrane potential were also detected. Terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling staining was applied to measure cell apoptosis, and messenger RNA and protein levels of apoptosis-related proteins (Fas ligand [Fasl], B-cell CLL/lymphoma [Bcl-2], p53) were also detected. Initially, sepsis rats exhibited decreased survival rate, but increased ejection fraction (EF), heart rate, and concentrations of TnT, cTnI, and CK-MB. Furthermore, decreased AT1R expression inactivated the MAPK signaling pathway (shown as decreased extracellular signal-regulated kinase and cyclic adenosine 3',5'-monophosphate response element binding protein expression), decreased EF, heart rate, and concentrations of TnT, cTnI, and CK-MB, but increased sepsis rat survival rate. Eventually, decreased AT1R expression inhibited myocardial cell apoptosis (shown as decreased apoptosis rate and p53 and Fasl expression as well as increased Bcl-2 expression). These findings indicated that AT1R silencing plays an inhibitory role in sepsis-induced myocardial injury by inhibiting the MAPK signaling pathway., (© 2019 Wiley Periodicals, Inc.)

The primary mechanism underlying sepsis‑induced cardiac dysfunction is loss of endothelial barrier function. Neuregulin‑1 (NRG‑1) exerts its functions on multiple targets. The present study aimed to identify the protective effects of NRG‑1 in myocardial cells, including endothelial, anti‑inflammatory and anti‑apoptotic effects. Subsequent to lipopolysaccharide (LPS)‑induced sepsis, rats were administered with either a vehicle or recombinant human NRG‑1 (rhNRG‑1; 10 µg/kg/day) for one or two days. H9c2 cardiomyoblasts were subjected to LPS (10 µg/ml) treatment for 12 and 24 h with or without rhNRG‑1 (1 µg/ml). Survival rates were recorded at 48 h following sepsis induction. The hemodynamic method was performed to evaluate cardiac function, and myocardial morphology was observed. Von Willebrand Factor levels were detected using an immunofluorescence assay. Serum levels of tumor necrosis factor α, interleukin‑6, intercellular cell adhesion molecule‑1 and vascular endothelial growth factor were detected using an enzyme‑linked immunosorbent assay; the reductase method was performed to detect serum nitric oxide levels. Apoptosis rates were determined using terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Ras homolog family member A (RhoA) and Rho‑associated protein kinase 1 (ROCK1) protein levels were assessed using western blotting. Transmission electron microscopy was used to observe endothelial cells and myocardial ultrastructure changes. Results revealed that NRG‑1‑treated rats displayed less myocardial damage compared with sham rats. NRG‑1 administration strengthened the barrier function of the vasculature, reduced the secretion of endothelial‑associated biomarkers and exerted anti‑inflammatory and anti‑apoptotic effects. In addition, NRG‑1 inhibited RhoA and ROCK1 signaling. The results revealed that NRG‑1 improves cardiac function, increases the survival rate of septic rats and exerts protective effects via multiple targets throughout the body. The present results contribute to the development of a novel approach to reverse damage to myocardial and endothelial cells during sepsis.

We present an operator-based factorization formula for the transverse energy-energy correlator (TEEC) hadron collider event shape in the back-to-back (dijet) limit. This factorization formula exhibits a remarkably symmetric form, being a projection onto a scattering plane of a more standard transverse momentum dependent factorization. Soft radiation is incorporated through a dijet soft function, which can be elegantly obtained to next-to-next-to-leading order (NNLO) due to the symmetries of the problem. We present numerical results for the TEEC resummed to next-to-next-to-leading logarithm (NNLL) matched to fixed order at the LHC. Our results constitute the first NNLL resummation for a dijet event shape observable at a hadron collider, and the first analytic result for a hadron collider dijet soft function at NNLO. We anticipate that the theoretical simplicity of the TEEC observable will make it indispensable for precision studies of QCD at the LHC, and as a playground for theoretical studies of factorization and its violation.

Background: The microbiomechanical properties of the meniscus influence the cell response to the surrounding biomechanical environment ​and are beneficial to understand meniscus repairing and healing. To date, however, this information remains ambiguous. This study aims to characterise the microbiomechanical properties of the meniscus after degeneration in a rabbit anterior cruciate ligament transection (ACLT) model and to analyse the corresponding histology at the macroscale and chemical composition., Methods: Twenty New Zealand white rabbits were used. Menisci were collected from the knee joints 4 and 8 weeks after the ACLT and from those of the corresponding control groups. The central portions of both medial and lateral menisci were investigated using atomic force microscopy, histological study, and an energy-dispersive spectrometer. The evaluation was conducted regionally within the inner, middle, and outer sites from the top layer (facing the femoral surface) to the bottom layer (facing the tibial surface) in both the lateral and medial menisci to obtain the site-dependent properties., Results: At 4 weeks after surgery, the dynamic elastic modulus at the microlevel increased significantly at both the top and bottom layers compared with the intact meniscus (P ​= ​0.021). At 8 weeks after surgery, the stiffening occurred in all regions (P ​= ​0.030). The medial meniscus showed greater change than the lateral meniscus. All these microbiomechanical alterations occurred before the histological findings at the macroscale., Conclusion: The microbiomechanical properties in the meniscus changed significantly after ACLT and were site dependent. Their alterations occurred before the histological changes of degeneration were observed., The Translational Potential of This Article: The results of our study indicated that degeneration promoted meniscus stiffening. Thus, they provide a better understanding of the disease process affecting the meniscus. Our results might be beneficial to understand how mechanical forces distribute throughout the healthy and pathologic joint. They indicate the possibility of early diagnosis using a minimally invasive arthroscopic tool, as well as they might guide treatment to the healthy and pathologic meniscus and joint., (© 2019 Published by Elsevier (Singapore) Pte Ltd on behalf of Chinese Speaking Orthopaedic Society.)

LACTB, a mitochondrial protein, was ubiquitously expressed in different mammalian tissues, such as liver, heart, and skeletal muscle. It has been shown that LACTB is downexpressed in breast cancers, and it suppresses the proliferation and promotes the apoptosis of breast cancers. However, its role in the progression and prognosis of glioma remains unknown. In this study, we analyzed the clinicopathological features and outcomes of LACTB expression in 98 glioma patients and investigated the effects of LACTB overexpression on the proliferation, invasion, and angiogenesis of glioma cells in vitro. We observed a significant decrease in LACTB expression in glioma, and downexpression of LACTB is correlated with a poor prognosis of glioma patients. Moreover, Cox regression analysis reveals that the LACTB is an independent prognostic indicator for glioma patients. Overexpression of LACTB could suppress the proliferation, invasion, and angiogenesis of glioma cells. In addition, overexpression of LACTB could inhibit the expression of PCNA, MMP2, MMP9, and VEGF. Taken together, these data indicate that LACTB may serve as a promising therapeutic target for gliomas.

Annulus fibrosus is critical to bear loads and resist fluid flow in the intervertebral disc. However, the detailed biomechanical mechanism of annulus fibrosus under abnormal loading is still ambiguous, especially at the micro and nano scales. This study aims to characterize the alterations of modulus at the nano scale of individual collagen fibrils in annulus fibrosus after in-situ immobilization, and the corresponding micro-biomechanics of annulus fibrosus. An immobilization model was used on the rat tail with an external fixation device. The elastic modulus of annulus fibrosus at both the nano- and micro-scale was examined using atomic force microscopy after fixation for 4 and 8 weeks, respectively. The fibrils in inner layer showed an alteration in elastic modulus from 91.38 ± 20.19 MPa in the intact annulus fibrosus to 110.64 ± 15.58 MPa (p < 0.001) at the nano scale after immobilization for 8 weeks, while the corresponding modulus at the micro scale also underwent a change from 0.33 ± 0.04 MPa to 0.47 ± 0.04 MPa (p < 0.001). The fibril disorder after immobilization was observed by hematoxylin/eosin staining. The gene expression of annulus fibrosus was also measured by real-time reverse transcription-polymerase chain reaction, which showed the upregulation of collagen II (p = 0.003) after immobilization. The results indicated that the immobilization not only influenced the individual fibril at the nanoscale, but also the micro-biomechanical property of annulus fibrosus which is critical to define the cell response to surrounding biomechanical environment. These alterations may also lead to the change in the mechanical property of the whole disc and the load-bearing function. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 9999:1-7, 2018., (© 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)