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In this study, we investigated how tau phosphorylation is regulated by protein kinase glycogen synthase kinase 3beta (GSK3 beta), protein kinase B (PKB), and protein phosphatase 2A (PP2A) in mouse N2a neuroblastoma cells. Results showed that GSK3 beta overexpression significantly increased PKB phosphorylation at the S473 site but not the T308 site. Neither GSK3 beta nor PKB overexpression could reduce the PP2AC phosphorylation at the Y307 site. In contrast, either PKB or GSK3 beta knockdown could increase PP2A phosphorylation at the Y307 site. PP2AC knockdown increased GSK3 beta phosphorylation at the S9 site but not at the Y216 site, and PKB phosphorylation at the T308 site but not at the S473 site. Tau phosphorylation at the S396 site was increased by GSK3 beta or PKB overexpression. Tau phosphorylation at the S214 site was only induced by PKB overexpression in the study. While GSK3 beta knockdown decreased tau phosphorylation at the S396 site, PKB knockdown increased tau phosphorylation at both the S396 and S214 sites. PP2AC knockdown decreased tau phosphorylation at the S396 and S214 sites. These findings suggest that tau phosphorylation at the S396 and S214 sites is differentially regulated by GSK3 beta, PKB, and PP2A in N2a cells. The final phosphorylation state of tau is possibly caused by the synergic action of the three enzymes. [ABSTRACT FROM AUTHOR]

Background and Purpose: Non-enhanced computed tomography (NECT) and computed tomography angiography (CTA) are useful for detecting aneurysmal subarachnoid hemorrhage (SAH) but challenging to identify ruptured aneurysms in cases of multiple aneurysms. We aimed to determine if the hypoattenuating berry sign (HBS) can identify ruptured aneurysms in SAH patients with multiple aneurysms., Methods: Patients who had multiple aneurysms and underwent NECT were retrospectively recruited. The HBS, blood score, size and location of aneurysm were independently analyzed. The attenuation value of HBS and surrounding SAH were recorded. The independent factors of HBS in determination of ruptured aneurysms were analyzed using multivariable logistic regression., Results: Fifty-three patients (mean age 64.2 ± 10.9 years, 83.0% female) with 112 aneurysms were enrolled. In the univariate analysis, aneurysm size, aneurysm status (ruptured), and blood score were significantly correlated with the occurrence of HBS. In the multivariate analysis, only aneurysm status showed a significant association with HBS. Aneurysms with HBS were larger than those without (6.8 ± 4.2 mm versus 4.2 ± 1.2 mm, P < 0.001), and those measured via NECT were larger than those measured via DSA (7.2 ± 3.8 mm vs. 6.8 ± 4.2 mm, P < 0.001). HBS was found in 51.8% of all aneurysms and in 87.7% of ruptured aneurysms on NECT. Raters had high agreement on aneurysm size (ICC = 0.829), HBS presence (kappa = 0.928), and blood score (kappa = 0.780)., Conclusions: The HBS can be used to detect ruptured aneurysm in patient with SAH and multiple aneurysms., Competing Interests: Declarations. Ethical approval: This study was approved by Yuebei People’s hospital (Ethics code: YBECKY(2024)-004). Guarantor: The scientific guarantor of this publication is Xin-Wei Zhou. Informed consent: Written informed consent was exempted due to the study design entailed no diagnostic tests or treatment. Conflict of interest: The authors declare that they have no conflicts of interest., (© 2025. The Author(s), under exclusive licence to American Society of Emergency Radiology (ASER).)

Competing Interests: Disclosures None.

Seven previously undescribed polyketide derivatives, fusariumtides A-G (1-7), together with three known analogues (8-10), were isolated from the culture extract of Fusarium asiaticum QA-6, an endophytic fungus obtained from the fresh stem tissue of the medicinal plant Artemisia argyi H. Lev. & Vaniot. Their structures were elucidated by detailed interpretation of 1D/2D NMR spectroscopic and mass spectrometric data, and the absolute configuration of compound 1 was established on the basis of X-ray crystallographic analysis and ECD and specific rotation (SR) calculations. The isolated compounds, which possessed a functionalized decalin moiety, were evaluated for antimicrobial activities. Compounds 1 and 10 exhibited broad-spectrum inhibitory activities against nine tested pathogenic bacteria with MIC values ranging from 1 to 64 μg/mL, while compound 8 showed potent inhibitory activities against aquatic pathogens Aeromonas hydrophilia, Pseudomonas aeruginosa, Vibrio harveyi, and V. vulnificus, which were comparable to/or stronger than those of the positive control chloramphenicol., 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 © 2025 Elsevier Ltd. All rights reserved.)

Obstructive sleep apnoea (OSA) and its associations with lung function., Background: OSA is highly prevalent and characterised by abnormal respiration during sleep. This large, population-based study aimed to investigate the associations between OSA and lung function in subjects aged 50-64 years., Method: The population-based Swedish CArdioPulmonary bioimage Study includes information on anthropometry, comorbidities and spirometry. The current analysis included data from three centres (Gothenburg, Umeå and Uppsala) on whole-night respiratory polygraphy as a meta-analysis examining the overall effect size of lung function on sleep apnoea severity, expressed as ß-coefficient after stratifying for sex and adjusting for age, waist circumference and smoking status., Results: Data from 9016 participants (54% women, age 58±4 years, body mass index 27±4 kg/m 2 ) with sleep recordings of good quality were included in the final analysis. Forced expiratory volume during 1 s (FEV 1 ) (ß=-0.10 (95% CI -0.16 to -0.03)), forced vital capacity (FVC) (-0.15 (-0.21 to -0.10)) and diffusion capacity for carbon monoxide (DL CO ) (-0.08 (-0.10 to -0.05)) were all negatively associated with the oxygen desaturation index (ODI) and also with per cent of registration with nocturnal oxygen saturation <90% FVC (-0.44 (-0.87 to -0.01)), FEV 1 (-0.86 (-1.36 to -0.36)) and DL CO (-0.47 (-0.60 to -0.35)). Additionally, a positive association was observed between FEV 1 (0.13 (0.05 to 0.22)) and DL CO (0.07 (0.04 to 0.09)) with the mean nocturnal saturation. There was a negative association between DL CO and apnoea-hypopnoea index, AHI, (ß=-0.04 (95% CI-0.06 to -0.03)), while no associations were found between FEV 1 or FVC and AHI., Conclusion: In OSA, lower lung function is more distinctly associated with the nocturnal hypoxic burden than AHI. Potential lung function impairment should be investigated in OSA patients with a high ODI relative to AHI., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Camellia nitidissima Chi is a popular ornamental plant because of its golden flowers, which contain flavonoids and carotenoids. To understand the regulatory mechanism of golden color formation, the metabolites of C. nitidissima petals at five different developmental stages were detected, a proteome map of petals was first constructed via tandem mass tag (TMT) analysis, and the accuracy of the sequencing data was validated via parallel reaction monitoring (PRM)., Results: Nineteen color components were detected, and most of these components were carotenoids that gradually accumulated, while some metabolites were flavonoids that were gradually depleted. A total of 97,647 spectra were obtained, and 6,789 quantifiable proteins were identified. Then, 1,319 differentially expressed proteins (DEPs) were found, 55 of which belong to the flavonoid and carotenoid pathways, as revealed by pairwise comparisons of protein expression levels across the five developmental stages. Notably, most DEPs involved in the synthesis of flavonoids, such as phenylalanine ammonium lyase and 4-coumarate-CoA ligase, were downregulated during petal development, whereas DEPs involved in carotenoid synthesis, such as phytoene synthase, 1-deoxy-D-xylulose-5-phosphate synthase, and β-cyclase, tended to be upregulated. Furthermore, protein‒protein interaction (PPI) network analysis revealed that these 55 DEPs formed two distinct PPI networks closely tied to the flavonoid and carotenoid synthesis pathways. Phytoene synthase and chalcone synthase exhibited extensive interactions with numerous other proteins and displayed high connectivity within the PPI networks, suggesting their pivotal biological functions in flavonoid and carotenoid biosynthesis., Conclusion: Proteomic data on the flavonoid and carotenoid biosynthesis pathways were obtained, and the regulatory roles of the DEPs were analyzed, which provided a theoretical basis for further understanding the golden color formation mechanism of C. nitidissima., (© 2024. The Author(s).)

Increasing evidence supported that oxidative stress induced by herniated lumbar disc played important role in the formation of lumbar disc herniation sciatica (LDHS), however, the neural mechanisms underlying LDHS need further clarification. Endomorphin-2 (EM2) is the endogenous ligand for mu-opioid receptor (MOR), and there is increasing evidence implicating the involvement of spinal EM2 in neuropathic pain. In this study, using an nucleus pulposus implantation induced LDHS rat model that displayed obvious mechanical allodynia, it was found that the expression of EM2 in dorsal root ganglion (DRG) and spinal cord was significantly decreased. It was further found that oxidative stress in DRG and spinal cord was significantly increased in LDHS rats, and the reduction of EM2 in DRG and spinal cord was determined by oxidative stress dominated increment of dipeptidylpeptidase IV activity. A systemic treatment with antioxidant could prevent the forming of mechanical allodynia in LDHS rats. In addition, MOR expression in DRG and spinal cord remained unchanged in LDHS rats. Intrathecal injection of MOR antagonist promoted pain behavior in LDHS rats, and the analgesic effect of intrathecal injection of EM2 was stronger than that of endomorphin-1 and morphine. Taken together, our findings suggest that oxidative stress mediated decrement of EM2 in DRG and spinal cord causes the loss of endogenous analgesic effects and enhances the pain sensation of LDHS., Competing Interests: Declaration of competing interest Each author listed in the manuscript had no conflicts of interest to declare in relation to this article., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Mazabraud's syndrome (MS) is a rare and slowly progressive benign disease characterized by the concurrent presence of fibrous dysplasia of bone and intramuscular myxoma, and is thought to be associated with mutations of the GNAS gene. To date, only about 100 cases of MS have been reported in the literature, but its standard treatment strategy remains unclear., Case Summary: We report two cases of MS in young women who underwent different treatments based on their symptoms and disease manifestations. The first patient, aged 37, received internal fixation and intravenous bisphosphonate for a pathological fracture of the right femoral neck, excision of a right vastus medialis myxoma was subsequently performed for pain control, and asymptomatic psoas myxomas were monitored without surgery. Genetic testing confirmed a GNAS gene mutation in this patient. The second patient, aged 24, underwent right vastus intermedius muscle myxoma resection, and conservative treatment for fibrous dysplasia of the ilium. These patients were followed-up for 17 months and 3 years, respectively, and are now in a stable condition., Conclusion: Various treatments have been selected for MS patients who suffer different symptoms. The main treatment for myxomas is surgical resection, while fibrous dysplasia is selectively treated if the patient experiences pathological fracture or severe pain. However, given the documented instances of malignant transformation of fibrous dysplasia in individuals with MS, close follow-up is necessary., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Performance of zirconium tritides used for hydrogen isotope storage is significantly changed under reactor environments. This can be attributed to the formation of various radiation-induced dislocations. To help gain insight, molecular dynamics simulations have been employed to investigate hydrogen isotope population in zirconium containing different types of edge dislocations. Our studies reveal that hydrogen isotope concentration is highest near the tensile side of dislocation cores and varies based on dislocation type. This increase in hydrogen isotope concentration can be explained by the Boltzmann equation based on calculations using swelling volume and pressure field, with significantly reduced computational cost. Strikingly, because hydrogen isotope in the compressive regions of dislocations is depleted, the overall hydrogen isotope content is found to be unchanged by dislocation formation. These results counter the previous view that the dislocation trapping effect increases hydrogen isotope solubility and provide an understanding of changes in hydrogen isotope pressure under reactor conditions. By elucidating the impact of dislocations on hydrogen isotope storage performance, this research offers insights for optimizing zirconium tritides in nuclear applications. and contributes to the advancement of hydrogen isotope storage materials., Competing Interests: 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.

Background: The existence of pancreatic cancer stem cells (PCSCs) results in limited survival benefits from current treatment options. There is a scarcity of effective agents for treating pancreatic cancer patients. Dehydroevodiamine (DeHE), a quinazoline alkaloid isolated from the traditional Chinese herb Evodiae fructus, exhibited potent inhibition of pancreatic ductal adenocarcinoma (PDAC) cell proliferation and tumor growth both in vitro and in vivo., Methods: The cytotoxic effect of DeHE on PDAC cells was assessed using CCK-8 and colony formation assays. The antitumor efficacy of DeHE were appraised in human PANC-1 xenograft mouse model. Sphere formation assay and flow cytometry were employed to quantify the tumor stemness. RNA-Seq analysis, drug affinity responsive target stability assay (DARTS), and RNA interference transfection were conducted to elucidate potential signaling pathways. Western blotting and immunohistochemistry were utilized to assess protein expression levels., Results: DeHE effectively inhibited PDAC cell proliferation and tumor growth in vitro and in vivo, and exhibited a better safety profile compared to the clinical drug gemcitabine (GEM). DeHE inhibited PCSCs, as evidenced by its suppression of self-renewal capabilities of PCSCs, reduced the proportion of ALDH + cells and downregulated stemness-associated proteins (Nanog, Sox-2, and Oct-4) both in vitro and in vivo. Furthermore, there is potential involvement of DDIT3 and its downstream DDIT3/TRIB3/AKT/mTOR pathway in the suppression of stemness characteristics within DeHE-treated PDAC cells. Additionally, results from the DARTS assay indicated that DeHE interacts with DDIT3, safeguarding it against degradation mediated by pronase. Notably, the inhibitory capabilities of DeHE on PDAC cell proliferation and tumor stemness were partially restored by siDDIT3 or the AKT activator SC-79., Conclusion: In summary, our study has identified DeHE, a novel antitumor natural product, as an activator of DDIT3 with the ability to suppress the AKT/mTOR pathway. This pathway is intricately linked to tumor cell proliferation and stemness characteristics in PDAC. These findings suggest that DeHE holds potential as a promising candidate for the development of innovative anticancer therapeutics., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Introduction: Aneurysmal subarachnoid hemorrhage (SAH) constitutes a life-threatening condition, and identifying the ruptured aneurysm is essential for further therapy. This study aimed to evaluate the diagnostic accuracy of hypo-attenuating berry sign (HBS) observed on computed tomography (CT) scan in distinguishing ruptured aneurysms., Methods: In this diagnostic accuracy study, patients who had SAH and underwent non-enhanced brain CT scan were recruited. The HBS was defined as a hypo-attenuating area with an identifiable border in the blood-filled hyper-dense subarachnoid space. The screening performance characteristics of HBS in identifying ruptured aneurysms were calculated considering the digital subtraction angiography (DSA) as the gold standard., Results: A total of 129 aneurysms in 131 patients were analyzed. The overall sensitivity and specificity of HBS in the diagnosis of aneurysms were determined to be 78.7% (95%CI: 73.1% - 83.4%) and 70.7% (95%CI: 54.3% - 83.4%), respectively. Notably, the sensitivity increased to 90.9% (95%CI: 84.3% - 95.0%) for aneurysms larger than 5mm. The level of inter-observer agreement for assessing the presence of HBS was found to be substantial (kappa=0.734). The diagnostic accuracy of HBS in individuals exhibited enhanced specificity, sensitivity, and reliability when evaluating patients with a solitary aneurysm or assessing ruptured aneurysms. The multivariate logistic regression analysis revealed a statistically significant relationship between aneurysm size and the presence of HBS (odds ratios of 1.667 (95%CI: 1.238 - 2.244; p < 0.001) and 1.696 (95%CI: 1.231 - 2.335; p = 0.001) for reader 1 and reader 2, respectively)., Conclusions: The HBS can serve as a simple and easy-to-use indicator for identifying a ruptured aneurysm and estimating its size in SAH patients.   ., Competing Interests: The authors declare that they have no conflicts of interest.

Background: Plasmodium vivax malaria, with the widest geographic distribution, can cause severe disease and death. Primaquine is the main licensed antimalarial drug that can kill hypnozoites. The dose-dependent acute haemolysis in individuals with glucose-6-phospate dehydrogenase (G6PD) deficiency is the main safety concern when using primaquine. The recommended treatment regimen for P. vivax malaria is chloroquine plus primaquine for 14 days (CQPQ14) in Myanmar. The study aimed to evaluate the therapeutic efficacy, safety and adherence for the regimen of artemisinin-naphthoquine plus primaquine for 3 days (ANPQ3) in patients with P. vivax infections compared to those with CQPQ14., Methods: The patients in the ANPQ3 group were given fixed-dose artemisinin-naphthoquine (a total 24.5 mg/kg bodyweight) plus a lower total primaquine dose (0.9 mg/kg bodyweight) for 3 days. The patients in the CQPQ14 group were given a total chloroquine dose of 30 mg/kg body weight for 3 days plus a total primaquine dose of 4.2 mg/kg bodyweight for 14 days. All patients were followed up for 365 days., Results: A total of 288 patients completed follow-up, 172 in the ANPQ3 group and 116 in the CQPQ14 group. The first recurrence patients were detected by day 58 in both groups. By day 182, 16 recurrences had been recorded: 12 (7.0%) patients in the ANPQ3 group and 4 (3.4%) in the CQPQ14 group. The difference in recurrence-free patients was 3.5 (-8.6 to 1.5) percentage points between ANPQ3 and CQPQ14 group (P = 0.2946). By day 365, the percentage of recurrence-free patients was not significant between the two groups (P = 0.2257). Mean fever and parasite clearance time of ANPQ3 group were shorter than those in CQPQ14 group (P ≤ 0.001). No severe adverse effect was observed in ANPQ3 group, but five (3.9%) patients had acute haemolysis in CQPQ14 group (P = 0.013). Medication percentage of ANPQ3 group was significantly higher than that of CQPQ14 group (P < 0.0001)., Conclusions: Both ANPQ3 and CQPQ14 promised clinical cure efficacy, and the radical cure efficacy was similar between the ANPQ3 and CQPQ14 group. ANPQ3 clears fever and parasites faster than CQPQ14. ANPQ3 is safer and shows better patient adherence to the regimen for treatment of P. vivax malaria along the China-Myanmar border., Trial Registration: ChiCTR-INR-17012523. Registered 31 August 2017, https://www.chictr.org.cn/showproj.html?proj=21352., (© 2024. The Author(s).)

The stimulator of interferon genes (STING) signaling pathway is crucial for the pathogenesis of autoimmune and inflammatory disorders, including acute lung injury (ALI). Apigenin (4[Formula: see text],5,7-trihydroxyflavone) is a natural flavonoid widely found in fruits, vegetables, and Chinese medicinal herbs that exhibits a range of pharmacological effects, such as antibacterial and anti-inflammatory activities. However, the efficacy of apigenin in STING pathway-mediated diseases remains unclear. Accordingly, this study screened Chinese medicines to identify potent agents that reduced the synthesis of type I interferons (IFNs). The results revealed apigenin as a potent compound with low cytotoxicity that markedly reduced the synthesis of type I IFNs in response to STING pathway agonists. Besides, apigenin markedly suppressed innate immune responses triggered by the STING agonist SR-717. Mechanistically, apigenin downregulated IFN beta 1 (IFNB1) expression mediated by the STING pathway via dose-dependent inhibition of STING expression, reduction of dimerization, nuclear translocation of phosphorylated IRF3, and disruption of the association between STING and IRF3. Moreover, apigenin effectively mitigated pathological pulmonary inflammation and lung edema in lipopolysaccharide (LPS)-induced ALI in mice. Apigenin further strongly attenuated the hallmarks of immoderate inflammation (interleukin (IL)-6, IL-1[Formula: see text], and tumor necrosis factor [Formula: see text]) and innate immune responses (IFNB1, C-X-C motif chemokine ligand 10, and IFN-stimulated gene 15) by preventing the activation of the STING/IRF3 pathway both in vitro and in vivo . Importantly, SR-717 significantly reversed the inhibitory effects of apigenin in LPS-induced THP1-Blue TM ISG macrophages. Collectively, apigenin effectively alleviated innate immune responses and mitigated inflammation in LPS-induced ALI via inhibition of the STING/IRF3 pathway. These findings suggest the potential of apigenin as a prophylactic and therapeutic candidate for managing STING-mediated diseases.

With the expansion of global energy problems and the deepening of research on oxygen reduction reaction (ORR) in alkaline media, the development of low cost and high electrocatalytic performance catalysts has become a research hotspot. In this study, a hexagonal Pd-C-MnOOH composite catalyst was prepared by using the triblock copolymer P123 as the reducing agent and protective agent, sucrose as the carbon source and self-made MnOOH as the carrier under hydrothermal conditions. When the Pd load is 20% and the C/MnOOH ratio is 1 : 1, the 20% Pd-C-MnOOH-1 : 1 catalyst obtained by the one-step method has the highest ORR activity and stability in the alkaline system. At 1600 rpm, the limiting diffusion current density and half-wave potential of the 20% Pd-C-MnOOH-1 : 1 electrocatalyst are -4.78 mA cm -2 and 0.84 V, respectively, which are better than those of the commercial 20%Pd/C catalyst. According to the Koutecky-Levich (K-L) equation and the linear fitting results, the electron transfer number of the 20%Pd-C-MnOOH-1 : 1 electrocatalyst for the oxygen reduction reaction is 3.8, which is similar to that of a 4-electron process. After 1000 cycles, the limiting diffusion current density of the 20%Pd-C-MnOOH-1 : 1 catalyst is -4.61 mA cm -2 , which only decreases by 3.7%, indicating that the 20%Pd-C-MnOOH-1 : 1 catalyst has good stability. The reason for the improvement of the ORR performance of the Pd-C-MnOOH composite catalyst is the improvement of the conductivity of the carbon layer formed by original carbonization, the regular hexagonal highly active Pd particles and the synergistic catalytic effect between Pd and MnOOH. The method of introducing triblock copolymers in the synthesis of oxides and metal-oxide composite catalysts is expected to be extended to other electrocatalysis fields.

Background: Phosphorus (P) and salt stress are common abiotic stressors that limit crop growth and development, but the response mechanism of soybean to low phosphorus (LP) and salt (S) combined stress remains unclear., Results: In this study, two soybean germplasms with similar salt tolerance but contrasting P-efficiency, A74 (salt-tolerant and P-efficient) and A6 (salt-tolerant and P-inefficient), were selected as materials. By combining physiochemical and transcriptional analysis, we aimed to elucidate the mechanism by which soybean maintains high P-efficiency under salt stress. In total, 14,075 differentially expressed genes were identified through pairwise comparison. PageMan analysis subsequently revealed several significantly enriched categories in the LP vs. control (CK) or low phosphorus + salt (LPS) vs. S comparative combination when compared to A6, in the case of A74. These categories included genes involved in mitochondrial electron transport, secondary metabolism, stress, misc, transcription factors and transport. Additionally, weighted correlation network analysis identified two modules that were highly correlated with acid phosphatase and antioxidant enzyme activity. Citrate synthase gene (CS), acyl-coenzyme A oxidase4 gene (ACX), cytokinin dehydrogenase 7 gene (CKXs), and two-component response regulator ARR2 gene (ARR2) were identified as the most central hub genes in these two modules., Conclusion: In summary, we have pinpointed the gene categories responsible for the LP response variations between the two salt-tolerant germplasms, which are mainly related to antioxidant, and P uptake process. Further, the discovery of the hub genes layed the foundation for further exploration of the molecular mechanism of salt-tolerant and P-efficient in soybean., (© 2023. The Author(s).)

Background: Appropriate malaria treatment-seeking behaviour (TSB) is critical for timely detecting malaria, prompt treatment, and prevention of onward transmission of the disease in a community. This study aimed to compare treatment-seeking behaviours between malaria patients and non-malaria febrile patients, and to analyse the factors associated with appropriate TSB along the China-Myanmar border., Methods: A cross-sectional study was carried out to investigate the appropriate TSB of microscopy-confirmed malaria patients versus non-malaria febrile (NMF) patients. An unconditional logistic regression analysis (LRA) was used to identify factors associated with appropriate TSB., Results: Among 223 malaria patients and 446 NMF patients, 129 (57.8%) of the malaria patients versus 163 (36.5%) of the NMF patients firstly sought treatment in health facilities without laboratory testing for malaria (P < 0.0001). A total of 85(38.1%) of the malaria patients versus 278 (62.3%) of the NMF patients had appropriate TSB, namely, seeking treatment in health facilities with laboratory testing for malaria within 48 h (P < 0.0001). Multivariate LRA identified that the malaria patients with Chinese nationality had less appropriate TSB compared to those with other nationalities (adjusted odds ratio [AOR]: 0.21, 95% confidence interval CI 0.07-0.68, P = 0.0097), and malaria patients residing in urban areas had more appropriate TSB compared to those living in rural areas (AOR: 2.16, 95%CI 1.06-4.39, P = 0.0337)., Conclusions: TSB was not appropriate in malaria patients. Chinese citizenship and rural residence were two independent factors associated with inappropriate malaria TSB. It is urgently necessary to improve appropriate malaria TSB through effective campaigns of information, education, and communication for malaria control in Myanmar and preventing reestablishment of malaria transmission in Yunnan, China., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Metabolic fitness of T cells is essential for their vitality, which is largely dependent on the behavior of the mitochondria. The nature of mitochondrial behavior in tumor-infiltrating T cells remains poorly understood. In this study, we show that mitofusin-2 (MFN2) expression is positively correlated with the prognosis of multiple cancers. Genetic ablation of Mfn2 in CD8 + T cells dampens mitochondrial metabolism and function and promotes tumor progression. In tumor-infiltrating CD8 + T cells, MFN2 enhances mitochondria-endoplasmic reticulum (ER) contact by interacting with ER-embedded Ca 2+ -ATPase SERCA2, facilitating the mitochondrial Ca 2+ influx required for efficient mitochondrial metabolism. MFN2 stimulates the ER Ca 2+ retrieval activity of SERCA2, thereby preventing excessive mitochondrial Ca 2+ accumulation and apoptosis. Elevating mitochondria-ER contact by increasing MFN2 in CD8 + T cells improves the efficacy of cancer immunotherapy. Thus, we reveal a tethering-and-buffering mechanism of organelle cross-talk that regulates the metabolic fitness of tumor-infiltrating CD8 + T cells and highlights the therapeutic potential of enhancing MFN2 expression to optimize T cell function.

Background: Rouleaux agglutination is a common cause of difficult blood typing, but it is rarely reported in patients with acute brain trauma., Methods: This article describes a 69-year-old male with head injury who was admitted to the hospital. Blood typing showed type O, Rh(D) positive, but the Rh(D) control was also positive. After ruling out the possibility of the patient having abnormal autoantibodies, it was suspected that rouleaux agglutination might be the cause. Microscopic examination of the specimen revealed rouleaux agglutination, which was believed to be the cause of the false-positive Rh(D) control result. The patient's red blood cells were treated with physiological saline and retested by microcolumn gel card testing., Results: The retest showed negative Rh(D) control results, indicating normal results. The patient subsequently received normal blood transfusion., Conclusions: Laboratory personnel should be aware of the possibility of difficult blood typing caused by rouleaux agglutination in various diseases, especially in relatively rare traumatic diseases.

The growth of helium bubbles impacts structural integrity of materials in nuclear applications. Understanding helium bubble nucleation and growth mechanisms is critical for improved material applications and aging predictions. Systematic molecular dynamics simulations have been performed to study helium bubble nucleation and growth mechanisms in Fe 70 Ni 11 Cr 19 stainless steels. First, helium cluster diffusivities are calculated at a variety of helium cluster sizes and temperatures for systems with and without dislocations. Second, the process of diffusion of helium atoms to join existing helium bubbles is not deterministic and is hence studied using ensemble simulations for systems with and without vacancies, interstitials, and dislocations. We find that bubble nucleation depends on diffusion of not only single helium atoms, but also small helium clusters. Defects such as vacancies and dislocations can significantly impact the diffusion kinetics due to the trapping effects. Vacancies always increase the time for helium atoms to join existing bubbles due to the short-range trapping effect. This promotes bubble nucleation as opposed to bubble growth. Interestingly, dislocations can create a long-range trapping effect that reduces the time for helium atoms to join existing bubbles. This can promote bubble growth within a certain region near dislocations., Competing Interests: There are no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)

Highland barley (HB) is an important cereal crop distributed in the plateau region. Bioactive peptides (BAPs) derived from cereal proteins have shown biological functions. However, the knowledge of highland barley peptide (HBP) is limited. This study aims to explore the immunomodulatory activity of HBP and the relationship between immunomodulatory activity and related gene expression through RNA-seq. Firstly, HBP is isolated from protease hydrolysates of HB protein, yielding 12.04% of crude HB protein. The molecular weight of HBP is about 1702 Da analyzed by gel filtration chromatography, and HBP has a specific amino acid sequence as Gln-Pro-Gln-Gln-Pro-Phe-Pro-Gln (QPQPFPQ) analyzed by LC-MS. Besides, HBP contains 42.20% hydrophobic amino acids and 10.86% basic amino acids. Next, the immunomodulatory activity of HBP in vitro shows that HBP enhances the phagocytosis of RAW264.7 macrophages, promotes nitric oxide (NO) production and the mRNA expression of pro-inflammatory genes including tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and inducible nitric oxide synthase (iNOS), and decreases the mRNA expression of anti-inflammatory gene, transforming growth factor β1 (TGF-β1). RNA-seq analysis reveals TNF and nuclear factor kappa B (NF-κB) pathways are upregulated, and RT-qPCR is performed to verify RNA-seq analysis. In conclusion, HBP activates RAW264.7 macrophages via TNF/NF-κB signaling pathway. HBP, as a significant immunomodulatory peptide, might be a promising resource for future functional foods., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The aim of this study was to evaluate the application potential of a recombinant fungal immunomodulatory protein from Ganoderma lucidum (rFIP-glu). First, a recombinant plasmid pPIC9K::FIP-glu-His was transferred into Pichia pastoris for the production of protein. The protein was then to assess its free radical scavenging abilities and the effect on the viability of both human immortalized keratinocytes (HaCaT cells) and mouse B16-F10 melanoma cells (B16 cells) in vitro , followed by the effect on the melanin synthesis of B16 cells. The results of SDS-PAGE and western blot showed that rFIP-glu was successfully expressed. Furtherly, a bioactivity assay in vitro indicated that the scavenging rate of 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals reached 84.5% at 6.0 mg/mL ( p ≤ 0.0001) of rFIP-glu, showing strong antioxidant activity. Subsequently, a safety evaluation demonstrated that rFIP-glu promoted the proliferation of HaCaT cells, with the cell viability reaching 124.3% at 48 μg/mL ( p ≤ 0.01), regarding the cell viability of B16 cells after exposure to rFIP-glu (48 μg/mL) significantly inhibited, to 80.7% ( p ≤ 0.01). Besides, rFIP-glu inhibited the melanin synthesis of B16 cells in a dose-dependent manner from 100-1000 μg/mL, and rFIP-glu at 500 μg/mL ( p ≤ 0.01) exhibited the highest intracellular melanin amount reduction of 16.8%. Furthermore, a mechanism analysis showed that rFIP-glu inhibited tyrosinase (TYR) activity by up-regulating the expression of the microphthalmia-associated transcription factor (MITF) and down-regulating the gene expression of TYR and tyrosinase-related protein-1 (TYRP-1), thus inhibiting melanin synthesis. The data implied that rFIP-glu had significant antioxidant activity and whitening potency. It should be used as raw materials for cosmeceutical applications.

The interplay between hydrogen and dislocations ( e.g. , core and elastic energies, and dislocation-dislocation interactions) has implications on hydrogen embrittlement but is poorly understood. Continuum models of hydrogen enhanced local plasticity have not considered the effect of hydrogen on dislocation core energies. Energy minimization atomistic simulations can only resolve dislocation core energies in hydrogen-free systems because hydrogen motion is omitted so hydrogen atmosphere formation can't occur. Additionally, previous studies focused more on face-centered-cubic than body-centered-cubic metals. Discrete dislocation dynamics studies of hydrogen-dislocation interactions assume isotropic elasticity, but the validity of this assumption isn't understood. We perform time-averaged molecular dynamics simulations to study the effect of hydrogen on dislocation energies in body-centered-cubic iron for several dislocation character angles. We see atmosphere formation and highly converged dislocation energies. We find that hydrogen reduces dislocation core energies but can increase or decrease elastic energies of isolated dislocations and dislocation-dislocation interaction energies depending on character angle. We also find that isotropic elasticity can be well fitted to dislocation energies obtained from simulations if the isotropic elastic constants are not constrained to their anisotropic counterparts. These results are relevant to ongoing efforts in understanding hydrogen embrittlement and provide a foundation for future work in this field.

High temperature and drought are abiotic stresses restricting many arthropods' survival and growth. Wolf spiders are poikilothermic arthropods that are vital in managing insects and pests. Nonetheless, investigating changes in spiders under temperature and drought stress are limited, especially at the molecular and gene expression levels. The study found that the combined effects of high temperature and drought stress significantly reduced survival rates and raised superoxide dismutase and malondialdehyde levels in the wolf spider Pardosa pseudoannulata. An integrated transcriptome and metabolome analysis showed that differentially expressed genes and metabolites were highly enriched in pathways involved in the proteolysis and oxidation-reduction process. The gene expression profiles displayed that heat shock protein (HSP) families (i.e., small heat shock protein, HSP70, HSP90, and HSP beta protein) were up-regulated under temperature and/or drought stresses. Additionally, a conjoint analysis revealed that under the combined stress, several important enzymes, including maltase-glucoamylase, glycerol-6-phosphate transporter, alanine-glyoxylate transaminase, and prostaglandin-H2 D-isomerase, were altered, affecting the metabolism of starch, sucrose, amino acids, and arachidonic acid. The protein interaction network further confirmed that under the combined stress, metabolic processes, peptide metabolic processes, and ATP generation from ADP were up-regulated, indicating that spiders could accelerate the metabolism of carbohydrates and proteins to combat stress and maintain homeostasis. Overall, this work showed that exposure to a combination of pressures might cause distinct defensive reactions in spiders and offered novel perspectives to research the molecular underpinnings of spider adaptation to a changing climate., 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 © 2022 Elsevier Ltd. All rights reserved.)

Proteins do not only serve as nutrients to fulfill the demand for food, but also are used as a source of bioactive proteins/polypeptides for regulating physical functions and promoting physical health. Female breast cancer has the highest incidence in the world and is a serious threat to women's health. Bioactive proteins/polypeptides exert strong anti-tumor effects and exhibit inhibition of multiple breast cancer cells. This review discussed the suppressing effects of bioactive proteins/polypeptides on breast cancer in vitro and in vivo, and their mechanisms of migration and invasion inhibition, apoptosis induction, and cell cycle arrest. This may contribute to providing a basis for the development of bioactive proteins/polypeptides for the treatment of breast cancer., Competing Interests: Conflict of interestThe 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., (© The Korean Society of Food Science and Technology 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

The investigation of the toxic effects of cadmium (Cd) on rice field invertebrates has attracted accumulating attention. Spider grants a novel insight into the impacts of Cd stress on invertebrates, but the effects of Cd-induced toxicity and molecular response mechanism of related metabolites in spider's egg sacs remain elusive. This investigation found that Cd stress distinctively decreased vitellogenin (Vg) content and hatched spiderlings numbers in the egg sac of Pardosa pseudoannulata. In addition, Cd stress exerted oxidative stress in the egg sac, manifested as the increase of superoxide dismutase and malondialdehyde levels. Further results showed that Cd exposure could affect egg sacs' energy metabolism, including protein and lipid contents. Metabolome analysis generated 73 up-regulated and 63 down-regulated differentially expressed metabolites (DEMs), mainly affecting phenylalanine metabolism, alpha-linolenic acid metabolism, pentose phosphate pathway, and biosynthesis of amino acids. Specifically, pathway analysis showed that Cd exposure down-regulated several key factors, including tyrosine, L-phenylalanine, O-phospho-L-serine, and L-cystathionine, and inhibited the metabolism of amino acids in the egg sacs. The subsequent correlation analysis found that three metabolite indicators, 9-Oxo-ODE, PG (17:0/18:2), and PE (17:0/20:5), were the dominant contributors to the egg sec's properties (i.e., Vg content and gained spiderlings). Collectively, this study hopes to provide valuable data for the protection of rice field spiders and offer novel perspectives for Cd pollution assessment and management., 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 © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

The flavonoids and phenolic acids in grape berries greatly influence the quality of wine. Various methods are used to shape and prune grapevines, but their effects on the flavonoids and phenolic acids remain unclear. The flavonoids and phenolic acids in the berry pericarps from grapevines pruned using three types of leaf canopy, namely, V-shaped, T-shaped, and vertical shoot-positioned (VSP) canopies, were compared in this study. Results showed that the V-shaped canopy was more favorable for the accumulation of flavonoids and phenolic acids. Transcriptome and metabolome analyses revealed that the differentially expressed genes (DEGs) and differentially regulated metabolites (DRMs) were significantly enriched in the flavonoid and phenylpropanoid biosynthesis pathways. A total of 96 flavonoids and 32 phenolic acids were detected among the DRMs. Their contents were higher in the V-shaped canopy than in the T-shaped and VSP canopies. Conjoint analysis of transcriptome and metabolome showed that nine DEGs (e.g., cytochrome P450 98A9 and 98A2) were significantly correlated to nine phenolic acids (e.g., gentisic acid and neochlorogenic acid) and three genes (i.e., chalcone isomerase, UDP-glycosyltransferase 88A1, and caffeoyl-CoA O-methyltransferase) significantly correlated to 15 flavonoids (e.g., baimaside and tricin-7-O-rutinoside). These genes may be involved in the regulation of various flavonoids and phenolic acids in grape berries, but their functions need validation. This study provides novel insights into the effects of leaf canopy on flavonoids and phenolic acids in the skin of grape berries and reveals the potential regulatory networks involved in this phenomenon., 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 © 2022 Elsevier Ltd. All rights reserved.)

Cadmium (Cd) is a kind of toxic heavy metal widely distributed in the environment, posing life-threatening challenges to organisms. The paddy field spider is a natural enemy of pests and an essential component of rice biodiversity. Nonetheless, the effects of Cd stress on the postembryonic development of spiders and its detailed mechanism remain to be investigated. In the present study, we found that Cd stress posed adverse impacts on the growth indicators (e.g., carapace length, development duration, and survival rate) and increased the levels of three antioxidants (i.e., superoxide dismutase, glutathione S-transferase, and glutathione peroxidase) in the spiderlings of Pirata subpiraticus. An in-depth transcriptome analysis was employed in the study, and the results displayed that differentially expressed genes (DEGs) involved in postembryonic morphogenesis, development involved in symbiotic interaction, postembryonic development, and growth were distinctively altered under Cd stress. Further enrichment analysis showed that Cd exposure could activate the apoptosis pathway in the spider via the up-regulation of several key factors, including caspase-10, α-tubulin, actin, etc. In addition, we demonstrated that the increased level of glutathione-related enzymes in spiderlings was caused by the activation of glutathione metabolic pathway. The altered hedgehog signaling pathway might affect cell proliferation, tissue patterning, and development of spiderlings. Further protein interaction network displayed that Cd stress could affect multiple biological processes in spiderlings, particularly cellular response to stimulus and system development. To sum up, this study can provide multi-level perspectives to understand the toxicity of Cd on the growth and development of spiders., 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 © 2022 Elsevier Inc. All rights reserved.)

Background: The World Health Organization (WHO) has certificated China malaria free, but imported malaria is a continuous challenge in preventing reintroduction of malaria in the border area of China. Understanding risk factors of malaria along China-Myanmar border is benefit for preventing reintroduction of malaria in China and achieving the WHO's malaria elimination goal in the Greater Mekong Subregion (GMS)., Methods: This is a case-control study with one malaria case matched to two controls, in which cases were microscopy-confirmed malaria patients and controls were feverish people with microscopy-excluded malaria. A matched logistic regression analysis (LRA) was used to identify risk factors associated with malaria infection., Results: From May 2016 through October 2017, the study recruited 223 malaria cases (152 in China and 71 in Myanmar) and 446 controls (304 in China and 142 in Myanmar). All the 152 cases recruited in China were imported malaria. Independent factors associated with malaria infection were overnight out of home in one month prior to attendance of health facilities (adjusted odd ratio [AOR] 13.37, 95% confidence interval [CI]: 6.32-28.28, P < 0.0001), staying overnight in rural lowland and foothill (AOR 2.73, 95% CI: 1.45-5.14, P = 0.0019), staying overnight at altitude < 500 m (AOR 5.66, 95% CI: 3.01-10.71, P < 0.0001) and streamlets ≤ 100 m (AOR9.98, 95% CI: 4.96-20.09, P < 0.0001) in the border areas of Myanmar; and people lacking of knowledge of malaria transmission (AOR 2.17, 95% CI: 1.42-3.32, P = 0.0004)., Conclusions: Malaria transmission is highly focalized in lowland and foothill in the border areas of Myanmar. The risk factors associated with malaria infection are overnight staying out of home, at low altitude areas, proximity to streamlets and lack of knowledge of malaria transmission. To prevent reintroduction of malaria transmission in China and achieve the WHO goal of malaria elimination in the GMS, cross-border collaboration is continuously necessary, and health education is sorely needed for people in China to maintain their malaria knowledge and vigilance, and in Myanmar to improve their ability of personal protection., (© 2022. The Author(s).)

Chinese Cordyceps is a valuable source of natural products with various therapeutic effects. It is rich in various active components, of which adenosine, cordycepin and polysaccharides have been confirmed with significant immunomodulatory and antitumor functions. However, the underlying antitumor mechanism remains poorly understood. In this review, we summarized and analyzed the chemical characteristics of the main components and their pharmacological effects and mechanism on immunomodulatory and antitumor functions. The analysis revealed that Chinese Cordyceps promotes immune cells' antitumor function by via upregulating immune responses and downregulating immunosuppression in the tumor microenvironment and resetting the immune cells' phenotype. Moreover, Chinese Cordyceps can inhibit the growth and metastasis of tumor cells by death (including apoptosis and autophagy) induction, cell-cycle arrest, and angiogenesis inhibition. Recent evidence has revealed that the signal pathways of mitogen-activated protein kinases (MAPKs), nuclear factor kappaB (NF-κB), cysteine-aspartic proteases (caspases) and serine/threonine kinase Akt were involved in the antitumor mechanisms. In conclusion, Chinese Cordyceps, one type of magic mushroom, can be potentially developed as immunomodulator and anticancer therapeutic agents., Competing Interests: The authors declare no conflict of interest.

Vincetoxicum junzifengense B.J. Ye and S.P. Chen 2022 is a newly described species which belongs to the genus Vincetoxicum in the family Apocynaceae. The complete plastid genome of Vincetoxicum junzifengense B.J. Ye and S.P. Chen 2022 was determined and analyzed in this study. The total chloroplast genome was 159,666 bp in length, consisting of a large single-copy region of 90,565 bp, a small single-copy region of 19,691 bp, and two inverted repeat regions of 24,705 bp. The genome contained 131 genes, including 85 protein-coding genes, 37 transfer RNA genes, and eight ribosomal RNA genes. Phylogenetic analysis indicated that V. junzifengense is sister to V . versicolor., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this article. The authors alone are responsible for the content and writing of the paper., (© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

By assessing and comparing the phenotypic changes on the stepwise acquisition of fluconazole resistant Candida albicans isolates, we could find and describe the relationship between drug resistance and biofilm formation ability in a series of clonal strains., Methods: We performed antifungal susceptibility of five drugs (fluconazole, itraconazole, voriconazole, caspofungin and amphotericin B) to further verify the antifungal activity of the six isolates in vitro . Then we combined hyphal formation assay, cell surface hydrophobicity test positively related to adherence ability, and biofilm assays in vitro to observe and compare the phenotypic characteristics of our six clonal strains., Results: Biofilm capability is enhanced for four drug- intermediate strains, whereas the initial susceptible strain and the final resistant strain are both poor in adherence, hyphal growth and biofilm formation., Conclusions: It was suggested that the biofilm formation ability were not absolutely related to the degree of fluconazole resistance., Competing Interests: Conflicts of interest: The authors reported no conflicts of interest., (Copyright © 2022 Hospital for Skin Diseases (Institute of Dermatology), Chinese Academy of Medical Sciences, and Chinese Medical Association, published by Wolters Kluwer, Inc.)

Background and Purpose: Intracranial aneurysms, a rare complication of radiation therapy, have been reported mainly in case reports or case series. We performed a multicenter, retrospective cohort study to investigate the characteristics of radiation-induced intracranial aneurysms., Materials and Methods: Data on 2641 patients with intracranial aneurysms were retrospectively collected from 3 hospitals between January 2005 and June 2014. An additional 1519 patients were recruited from a single center between July 2014 and March 2020. Aneurysms in patients with a history of radiation therapy for at least 6 months were defined as radiation-related aneurysms. Patients' demographic profiles, clinical characteristics, and aneurysm parameters detected on CTA were compared between radiation-related and control groups., Results: Of the 4160 patients, the average age was 57.9 (SD, 13.5) years, 2406 (57.8%) were women, 477 (11.5%) had multiple aneurysms, 3009 (72.3%) had SAH, and 34 (0.8%) had radiation-related aneurysms. The male-to-female ratio in the radiation-related group was significantly higher than that in the control group (2.4:1 versus 0.72:1, P = .001). The mean age of the radiation-related group was significantly younger than in the control group (51.4 [SD, 15.0] years versus 58.2 [SD, 13.5] years, P = .003). More patients in the radiation-related group presented with SAH than in the control group (without age and sex matching, 88.2% versus 72.2%, P = .037; with age and sex matching, 88.2% versus 58.8%, P = .006). Of the 4813 intracranial aneurysms, only 43 (0.9%) aneurysms were categorized as in the radiation-related group, whereas 4770 (99.1%) aneurysms constituted the control group. Compared with the control group, there was a significantly higher proportion of sidewall aneurysms (46.5% versus 32.3%, P = .048) and a predilection for aneurysms involving the ICA and posterior circulation arteries (72.1% versus 52.2%, P = .046) in the radiation-related group., Conclusions: Compared with the control group, radiation-related aneurysms are more prone to occur in men and young patients, with a higher percentage of sidewall aneurysms located in the ICA and posterior circulation arteries. Furthermore, SAH is highly prevalent in patients with radiation-induced aneurysms, indicating that dedicated screening for aneurysms after radiation therapy is necessary, but further studies are needed to determine when and how to screen., (© 2022 by American Journal of Neuroradiology.)

Whether amino acids act on cellular insulin signaling remains unclear, given that increased circulating amino acid levels are associated with the onset of type 2 diabetes (T2D). Here, we report that phenylalanine modifies insulin receptor beta (IRβ) and inactivates insulin signaling and glucose uptake. Mice fed phenylalanine-rich chow or phenylalanine-producing aspartame or overexpressing human phenylalanyl-tRNA synthetase (hFARS) develop insulin resistance and T2D symptoms. Mechanistically, FARS phenylalanylate lysine 1057/1079 of IRβ (F-K1057/1079), inactivating IRβ and preventing insulin from promoting glucose uptake by cells. SIRT1 reverse F-K1057/1079 and counteract the insulin-inactivating effects of hFARS and phenylalanine. F-K1057/1079 and SIRT1 levels in white blood cells from T2D patients are positively and negatively correlated with T2D onset, respectively. Blocking F-K1057/1079 with phenylalaninol sensitizes insulin signaling and relieves T2D symptoms in hFARS-transgenic and db/db mice. These findings shed light on the activation of insulin signaling and T2D progression through inhibition of phenylalanylation., (© 2022. The Author(s).)

Grid management is a grassroots governance strategy widely implemented in China since 2004 to improve the government's efficiency to actively find and solve problems among populated regions. A grid-based strategy surveillancing high-risk groups, including mobile and migrant populations (MMPs), in the China-Myanmar border region has played an indispensable role in promoting and consolidating the malaria elimination efforts by tracking and timely identification of potential importation or re-establishment of malaria among MMPs. A sequential mixed methods was implementated to explore the operational mechanism and best practices of the grid-based strategy including through the focus group discussions (FGDs), comparison of before and after the implementation of a grid-based strategy in the field sites, and data collection from the local health system.This paper distills the implementation mechanism and highlights the role of the grid-based strategy in the elimination and prevention of re-establishment of malaria transmission., (© 2022. The Author(s).)

Objective: To explore the prognostic factors of adult ventricle glioma (AVG) and to construct and evaluate a survival-related prognostic nomogram model, which could provide further reference for the clinical management of AVG patients., Methods: The patients covered in the study were selected from the Surveillance Epidemiology and End Results (SEER) database (1973-2016). They all had definite histological diagnosis of AVG. They were assigned randomly to the training cohort and the validation cohort by random number table at a 2/1 ratio. Survival analysis was performed by Kaplan-Meier analysis. Cox regression analysis was employed to determine the independent prognostic factors for overall survival (OS) and cancer-specific survival (CSS). Then, integrating the basic characteristics of patients, the survival-related nomogram predictive model for OS and CSS in the training cohort was constructed, respectively. After that, internal cross validation and external validation of the model were carried out with the training cohort and the validation cohort in succession. The authenticity and reliability of the nomogram model were evaluated by calculating the concordance index (C-index). Calibration plots were constructed to assess the agreement between the predicted values and the observed values in the training cohort and the validation cohort., Results: A total of 369 AVG patients, including 218 males and 151 females, were included. The median age of the patients was 53. According to the WHO classification of gliomas, 66 (17.9%) patients had grade Ⅱ gliomas, 73 (19.8%) had grade Ⅲ gliomas, and 230 (62.3%) had grade Ⅳ gliomas. Regarding the extent of resection (EOR), 59 (16.0%) had gross total resection (GTR) and 145 (39.3%) had subtotal resection (STR) or partial resection (PR). Of all the patients, 167 (45.3%) received postoperative radiotherapy and 143 (38.8%) received postoperative chemotherapy. Patients were randomized into the training cohort ( n =246) and the validation cohort ( n =123), and there was no significant difference ( P >0.05) in the basic clinical characteristics between the training cohort and the validation cohort. In the training cohort, Cox regression analysis revealed that the independent prognostic factors for OS and CSS included age≥65, grades Ⅲ and Ⅳ according to the WHO classification of gliomas, and not receiving radiotherapy. Furthermore, 5 variables, including age, gender, WHO grades, surgery, and radiotherapy, were used to construct the nomogram model for predicting 6-month, 1-year, and 2-year OS and CSS. The results of internal cross validation in the training cohort showed that the C-indexes of OS and CSS were 0.758 and 0.765, respectively. The external validation results of the validation cohort showed that the C-indexes of OS and CSS were 0.733 and 0.719, respectively. Calibration plots for 6-month, 1-year, and 2-year OS in the training cohort showed relatively good agreement, while in the validation cohort the agreement was relatively low. The 6-month, 1-year, and 2-year CSS calibration plots had results similar to the calibration plots of OS., Conclusion: This nomogram predictive model of OS and CSS showed moderately reliable predictive performance, providing helpful reference information for clinicians to make quick and simple assessment of the survival probability of AVG patients., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)

Deep brain stimulation (DBS) is a reversible treatment for chorea-acanthocytosis (ChAc). Its safety and efficacy remain elusive due to the low prevalence of ChAc. We aimed to investigate the safety and efficacy of DBS for ChAc by systematically reviewing literature through PubMed and EMBASE. Inclusion criteria were reports on the efficacy or safety of DBS for ChAc and English language articles, and exclusion criteria were other movement disorders, non-human subjects, and studies without original data. Most studies were published as case reports, and we therefore pooled these cases in one cohort. Twenty studies with 34 patients were included. The mean age of symptom onset was 29.3 years (range, 17-48). The median follow-up was 12 months (range, 2-84). Twenty-nine patients underwent GPi-DBS, two received STN-DBS, and one underwent Vop-DBS. Electrodes were implanted into the ventralis oralis complex of the thalamus and the pallidal in two patients. Symptoms seemed to be easier relieved in chorea (88.5%) and dystonia (76.9%) but dysarthria of most patients (85.7%) was no response after DBS. The Unified Huntington's Disease Rating Scale-Motor Score was used to assess the efficacy of DBS in 25 patients; the mean score decreased from 43.2 to 22.3 and the median improvement rate was 46.7%. Of 24 patients with data on adverse events, complications occurred in 9 patients (37.5%; mostly transient and mild events). DBS is a promising treatment for ChAc with satisfactory efficacy and safety based on the review. Pallidal and thalamic DBS have been applied in ChAc; GPi-DBS seems to be more widely used., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background and Aim: Carbapenem resistance has become a major obstacle in combating Acinetobacter baumannii infections. Although enzymatic degradation by β-lactamases is the pivotal mechanism of carbapenem resistance, porin deficiency has also been implicated in the mechanism. In this study, outer membrane proteins (OMPs) pattern of a clinical multidrug-resistant A. baumannii isolate were analysed in order to attain a deeper understanding of carbapenem-resistance strategies., Methods: OMPs extracts, respectively, separated from carbapenem-resistant and -susceptible clinical A. baumannii isolates were compared using two-dimensional polyacrylamide gel electrophoresis. Differentially expressed proteins were identified by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF)., Results: Twenty-three differently expressed proteins were identified between the resistant and susceptible isolates. Among them, six were annotated convincingly as OMPs in UniProt database. CarO was found absent from the resistant isolate and the expression levels of Omp33-36 and Omp25 were significantly lower than that in the susceptible counterpart. Strikingly, a LysM domain/BON superfamily protein, which has been linked to carbapenem resistance in Klebsiella pneumoniae, was found underexpressed by tenfold in the resistant isolate., Conclusion: Our study verified some porins which have been proven to play an important role in bacterial resistance against carbapenems. Underexpression of the LysM domain/BON superfamily protein may indicate its possible engagement in bacterial drug resistance, but its actual role requires more investigation., (© 2022 The Society for Applied Microbiology.)

Alzheimer's disease (AD) is the most common cause of neurodegenerative dementia and one of the top medical concerns worldwide. Currently, the approved drugs to treat AD are effective only in treating the symptoms, but do not cure or prevent AD. Although the exact causes of AD are not understood, it is recognized that tau aggregation in neurons plays a key role. Chuanxiong Rhizoma (CR) has been widely reported as effective for brain diseases such as dementia. Thus, we explored the protections of CR in AD by a tau pathogenesis-based network pharmacology approach. According to ultra-HPLC with triple quadrupole mass spectrometry data and Lipinski's rule of five, 18 bioactive phytochemicals of CR were screened out. They were shown corresponding to 127 tau pathogenesis-related targets, among which VEGFA, IL1B, CTNNB1, JUN, ESR1, STAT3, APP, BCL2L1, PTGS2, and PPARG were identified as the core ones. We further analyzed the specific actions of CR-active phytochemicals on tau pathogenesis from the aspects of tau aggregation and tau-mediated toxicities. It was shown that neocnidilide, ferulic acid, coniferyl ferulate, levistilide A, Z-ligustilide, butylidenephthalide, and caffeic acid can be effective in reversing tau hyperphosphorylation. Neocnidilide, senkyunolide A, butylphthalide, butylidenephthalide, Z-ligustilide, and L-tryptophan may be effective in promoting lysosome-associated degradation of tau, and levistilide A, neocnidilide, ferulic acid, L-tryptophan, senkyunolide A, Z-ligustilide, and butylidenephthalide may antagonize tau-mediated impairments of intracellular transport, axon and synaptic damages, and neuron death (especially apoptosis). The present study suggests that acting on tau aggregation and tau-mediated toxicities is part of the therapeutic mechanism of CR against AD., 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 Zeng, Su, Ye, Qiu, Shi, Wang, Zhou and Tian.)

Presently, the treatment options for ischemic stroke (IS) are limited due to the complicated pathological process of the disease. Chuanxiong Rhizome (CR), also known as Conioselinum anthriscoides "Chuanxiong" (rhizome), is the most widely used traditional Chinese medicine for treating stroke. This study aimed to uncover the key phytochemicals and biological functions of CR against IS through a network pharmacology approach combining with IS pathophysiology analysis. We employed permanent unilateral common carotid artery ligation to construct a mouse model of global cerebral ischemia and found that cerebral ischemia injuries were improved after 7 days of gavage treatment of CR (1,300 mg/kg/day). CR exerts protective effects on neurons mainly by acting on targets related to synaptic structure, synaptic function, neuronal survival and neuronal growth. A total of 18 phytochemicals from CR based on UHPLC-MS/MS that corresponded to 85 anti-IS targets. Coniferyl ferulate, neocnidilide and ferulic acid were identified as the key phytochemicals of CR against IS. Its brain protective effects involve anti-inflammatory, anti-oxidative stress, and anti-cell death activities and improves blood circulation. Additionally, the two most important synergistic effects of CR phytochemicals in treating IS are prevention of infection and regulation of blood pressure. In brain samples of Sham mice, L-tryptophan and vanillin were detected, while L-tryptophan, gallic acid, vanillin and cryptochlorogenic acid were detected in IS mice by UHPLC-MS/MS. Our findings provide a pathophysiology relevant pharmacological basis for further researches on IS therapeutic drugs., 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 © 2021 Zeng, Yi, Su, Ye, Sun, Zhou, Lu, Shi and Tian.)

Amyloid-β (Aβ) accumulating is considered as a causative factor for formation of senile plaque in Alzheimer's disease (AD), but its mechanism is still elusive. The Nicotinamide mononucleotide adenylyltransferase 2 (Nmnat2), a key redox cofactor for energy metabolism, is reduced in AD. Accumulative evidence has shown that the decrease of α-secretase activity, a disintegrin and metalloprotease domain 10 (ADAM10), is responsible for the increase of Aβ productions in AD patient's brain. Here, we observe that the activity of α-secretase ADAM10 and levels of Nmnat2 are significantly decreased, meanwhile there is a simultaneous elevation of Aβ in Tg2576 mice. Over-expression of Nmnat2 increases the mRNA expression of α-secretase ADAM10 and its activity and inhibits Aβ production in N2a/APPswe cells, which can be abolished by Compound C, an AMPK antagonist, suggesting that AMPK is involved in over-expression of Nmnat2 against Aβ production. The further assays demonstrate that Nmnat2 activates AMPK by up-regulating the ratio of NAD + /NADH, moreover AMPK agonist AICAR can also increase ADAM10 activity and reduces Aβ1-40/1-42. Taken together, Nmnat2 suppresses Aβ production and up-regulates ADAM10 in AMPK activity-dependent manner, suggesting that Nmnat2 may serve as a new potential target in arresting AD.

A perfect PtCu nanocube with partial hollow structure was prepared by hydrothermal reaction and its electrocatalytic methanol oxidation reaction (MOR) was studied. The appropriate concentration of shape-control additives KI and triblock pluronic copolymers, poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO 19 -PPO 69 -PEO 19 ) (P123) play crucial roles in the final product morphology. The PtCu nanocubes can be perfectly in situ immobilizedonto graphene under the action of P123 while the structure and cubic morphologyremain unchanged. The electrochemical tests suggest that the obtained PtCu nanocube (PtCu-NCb) exhibits better MOR activity and stability than PtCu hexagon nanosheet (PtCu-NSt), PtCu nanoellipsoid (PtCu-NEs) and commercial Pt/C in alkaline medium. When in situ immobilized onto graphene, the MOR catalytic activity and stability of PtCu cubes are further improved. The markedly enhanced electrocatalytic activity and durability maybe attributed to the special cubic morphology with partial hollow structure enclosed by highly efficient facet and the probably the synergistic effect of PtCu and intermediate state CuI decorated on the surface and graphene., 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 © 2021 Elsevier Inc. All rights reserved.)

Ethnopharmacological Relevance: Chinese Cordyceps (DongChong XiaCao), a parasitic complex of a fungus Ophiocordyceps sinensis and a caterpillar, is a traditional Chinese medicine. Polysaccharides extracted from O. sinensis have immunomodulatory effects on macrophages. However, the mechanism of polysaccharides on macrophage and the composition of polysaccharides are not known., Aim of Study: We aimed to investigate composition and structure of the intracellular polysaccharides from O. sinensis mycelia (designed as OSP), and evaluate its the immunomodulatory effect on macrophages and its underlying mechanism., Materials and Methods: We performed a liquid-state fermentation of O. sinensis to produce mycelia. The DEAE-Sephadex-A25 cellulose column and Sephadex-G100 gel column chromatography were employed to purify and character the intracellular OSP. Macrophages RAW264.7 cells were employed to evaluate OSP's immunomodulatory activity and the possible mechanism responsible for the activation of macrophages in vitro., Results: The average molecular weight of OSP was distributed at 27,972 Da, OSP was composed of xylose, mannose, glucose, and galactose with the ratio of 2.9 : 6.6 : 166 : 2.6, with a trace amount of fucose, arabinose and rhamnose. The phagocytosis of RAW264.7 cells was improved significantly and remarkable changes were observed in the morphology with OSP-treated cells. Real-time quantitative polymerase chain reaction (RT-qPCR) analysis demonstrated that OSP had an ability to regulate the mRNA expression of pro-inflammatory and anti-inflammatory cytokines, and to induce the mRNA expression level of iNOS in a concentration dependent manner in RAW264.7 cells. Western blotting analysis showed that the regulation of NO and cytokines was mediated through mitogen-activated protein kinase (MAPK) and PI3K/Akt signaling pathways., Conclusion: This study demonstrated that OSP was with a capacity to activate macrophage cells RAW264.7 for an improvement of immunomodulation activities, which was through regulation of inflammatory mediators via MAPK and PI3K/Akt signaling pathways., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Osteoporosis (OP) behaves in different manners in different parts of the skeleton. This study aims to investigate the effects of curcumin on bone mass of the mandibular and femur from ovariectomized OP rats and to validate whether enhancer of zeste homolog 2 (EZH2)/Wnt/β-Catenin pathway is involved in this process. Curcumin was administered intragastrically into ovariectomized rats for 12 weeks. The bone parameters and the morphology of the trabecular bone of the left mandible and left femur were assessed by micro-computed tomography assay. Morphological changes of the left mandible and left femur were evaluated by hematoxylin and eosin staining. The mRNA levels of EZH2, β-Catenin, and Runx2 in the right mandible and right femur were examined by quantitative real-time polymerase chain reaction. Immunohistochemistry was performed to assess EZH2 expression. Both the mandible and femur exhibited OP-like changes in ovariectomized rats, while the mandible bone resorption was less than the femur bone resorption. Curcumin intragastric administration improved bone microstructure and promoted bone formation in the mandible and femur. Curcumin inhibited EZH2 mRNA level and induced that of β-Catenin and Runx2 in the mandible and femur. Collectively, curcumin exerts protective effects against OP, possibly by regulating the EZH2/Wnt/β-Catenin pathway., (© 2021 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia on behalf of Kaohsiung Medical University.)

Cervical cancer is a common public health issue with high morbidity worldwide. Paeonol (Pae) has been recognized as a traditional Chinese medicine used for the treatment of various cancer types. However, whether Pae could exert a protective effect on cervical cancer remains to be investigated. The aim of the present study was to explore the role of Pae in cervical cancer cells and identify the potential mechanism. Cell Counting Kit‑8 and colony‑formation assays were conducted to test the proliferation of HeLa cells. Additionally, wound healing and transwell assays were used to detect the migratory and invasive abilities of cells. The plasmid that overexpressed 5‑lipoxygenase (5‑LO) or control vector was constructed and transfected into the cells. Subsequently, flow cytometry was used to monitor the apoptotic rate of cells. The expression levels of apoptosis‑associated proteins and 5‑LO were detected using western blot analysis. Reverse transcription‑quantitative PCR analysis detected the expression of 5‑LO. Pae inhibited the proliferation, invasion and migration of HeLa cells, promoted cell apoptosis and downregulated the expression of 5‑LO. Overexpression of 5‑LO, however, attenuated these effects. Thus, Pae could inhibit the proliferation, migration and invasion, as well as promote apoptosis of HeLa cells by regulating the expression of 5‑LO.

The global health emergency generated by coronavirus disease-2019 has prompted the search for immunomodulatory agents. There are many potential natural products for drug discovery and development to tackle this disease. One of these candidates is the Ganoderma lucidum fungal immunomodulatory protein (FIP-glu). In the present study, we clarify the influences of N-linked glycans on the improvement of anti-inflammatory activity and the potential mechanisms of action. Four proteins, including FIP-glu (WT) and its mutants N31S, T36N and N31S/T36N, were successfully expressed in P. pastoris, of which T36N and N31S/T36N were glycoproteins. After treatment with peptide-N-glycosidase F, the results of SDS-PAGE and Western blot showed that the glycan moiety was removed completely, indicating that the glycan moiety was N-linked. This was also demonstrated by UPLC-qTOF-MS. The cytotoxicity assay showed that N-linked glycans decreased the cytotoxicity of WT; while, the RT-qPCR assay showed that N-glycosylated WT regulated the mRNA expression of IL-6 and TGF-β1. The Western blot results showed that N-glycosylated WT reduced the phosphorylation level of p38 MAPK. In conclusion, our findings revealed a novel mechanism by which N-glycosylation of FIP-glu improved its anti-inflammatory activity through the regulation of the expression of inflammatory cytokines in RAW264.7 via inhibition of p38 MAPK phosphorylation. It was proved that N-glycosylation significantly improved the functional properties of FIP-glu, providing theoretical and technical support for expanding the application of FIPs in the food and pharmaceutical industries.

Carotane sesquiterpenes are commonly found in plants but are infrequently reported in the fungal kingdom. Chemical investigation of Trichoderma virens QA-8, an endophytic fungus associated with the inner root tissue of the grown medicinal herb Artemisia argyi H. Lév. and Vaniot, resulted in the isolation and characterization of five new carotane sesquiterpenes trichocarotins I-M ( 1 - 5 ), which have diverse substitution patterns, and seven known related analogues ( 6 - 12 ). The structures of these compounds were established on the basis of a detailed interpretation of their NMR and mass spectroscopic data, and the structures including the relative and absolute configurations of compounds 1 - 3 , 5 , 9 , and 10 were confirmed by X-ray crystallographic analysis. In the antibacterial assays, all isolates exhibited potent activity against Escherichia coli EMBLC-1, with MIC values ranging from 0.5 to 32 µg/mL, while 7 β -hydroxy CAF-603 ( 7 ) strongly inhibited Micrococcus luteus QDIO-3 (MIC = 0.5 µg/mL). Structure-activity relationships of these compounds were discussed. The results from this study demonstrate that the endophytic fungus T. virens QA-8 from the planted medicinal herb A. argyi is a rich source of antibacterial carotane sesquiterpenes, and some of them might be interesting for further study to be developed as novel antibacterial agents.

Dislocation core energy is an important property in materials mechanics but can only be obtained from atomistic simulations. Periodic boundary conditions are ideally suited for atomistic calculations of dislocation energies but have faced two major challenges. First, viable methods to extract core energies from atomistic data of total energies have been developed only for non-dissociated dislocations whereas realistic dislocations are often dissociated into partials. Second, core energy is a function of dislocation character angle. This functional dependence can only be revealed through calculations at a variety of character angles. This requires both additional computational resources and a robust method to implement arbitrary character angles. Here a new procedure has been developed to overcome both challenges. By applying this approach, we have calculated 22 core energies of dissociated dislocations in aluminium over the entire character angle range between 0° and 90°. In addition to the discrete core energy data for dissociated dislocations, we found that core energy can be approximated by a continuous function of character angle. Specifically, our dissociated dislocation core energies have been well fitted to a polynomial Sinoidal function of character angle. We have also discovered that there exists a critical system dimension below which dislocation core energies cannot be calculated due to dislocation transformation.