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The draining of brain interstitial fluid (ISF) to cerebrospinal fluid (CSF) and the subsequent draining of CSF to meningeal lymphatics is well‐known. Nonetheless, its role in the development of glioma is a remarkable finding that has to be extensively understood. The glymphatic system (GS) collects CSF from the subarachnoid space and brain ISF through aquaporin‐4 (AQP4) water channels. The glial limiting membrane and the perivascular astrocyte‐end‐feet membrane both have elevated levels of AQP4. CSF is thought to drain through the nerve sheaths of the olfactory and other cranial nerves as well as spinal meningeal lymphatics via dorsal or basal lymphatic vessels. Meningeal lymphatic vessels (MLVs) exist below the skull in the dorsal and basal regions. In this view, MLVs offer a pathway to drain macromolecules and traffic immunological cells from the CNS into cervical lymph nodes (CLNs), and thus can be used as a candidate curing strategy against glioma and other associated complications, such as neuro‐inflammation. Taken together, the lymphatic drainage system could provide a route or approach for drug targeting of glioma and other neurological conditions. Nevertheless, its pathophysiological role in glioma remains elusive, which needs extensive research. The current review aims to explore the lymphatic drainage system, its role in glioma progression, and possible therapeutic techniques that target MLVs in the CNS. [ABSTRACT FROM AUTHOR]

Objective: Papillary thyroid microcarcinoma (PTMC) has a good prognosis and a long survival time, surgery is the common treatment including total thyroidectomy (TT) and unilateral lobectomy (LT), but recent studies showed that TT does not show an advantage over LT for PTMC in preventing cancer recurrence and reducing mortality. Given this, the health‐related quality of life (HRQoL) has become one of the important factors that physicians must consider when making treatment decisions. The aim of this study was to compare the HRQoL of patients between undergoing TT and LT. Methods: From October 2019 to December 2019, 69 PTMC patients were enrolled in our study, including 34 in the LT group and 35 in the TT group, respectively. We used three questionnaires which included the 36‐item short‐form health survey (SF‐36), thyroid cancer‐specific quality of life (THYCA‐QOL), and Fear of Progression Questionnaire‐Short Form (FoP‐Q‐SF) for each patient to evaluate their scores of HRQoL. Results: According to the SF‐36, the scores of the domain for the role limitation due to physical problems, emotional problems, and social function (RP, RE, and SF) as well as Physical Component Summary (PCS) and Mental Component Summary (MCS) showed a significant negative linear association between the LT group and TT group: RP (coefficient [coef]: −33.953 [confidence interval (CI) −51.187 to −16.720], p < 0.001, RE (coef: −21.633 [CI −39.500 to −3.766], p = 0.018), SF (coef: −10.169 [CI −19.586 to −0.752], p = 0.035)and PCS (coef: −10.571 [CI −17.768 to −3.373], p = 0.005), MCS (coef: −10.694 [CI −19.465 to −1.923], p = 0.018). The THYCA‐QOL showed that the scores of the TT group were higher than that of the LT group in the problem of scar (coef: 16.245 [CI 1.697 to 30.794], p = 0.029 according to the multivariate analysis), suggesting a higher level of complaint in the TT group. There was no statistically significant difference in the scores of FoP‐Q‐SF between the two groups. Conclusions: In patients with PTMC, LT offers an advantage over TT in terms of HRQoL, which supports the role of LT as an alternative strategy to TT. [ABSTRACT FROM AUTHOR]

Background: Wrinkle formation is the most visible characteristic of facial aging. Radiofrequency (RF) technology is currently utilized to reduce facial wrinkles and contribute to skin rejuvenation. Objective: To analyze the efficacy and safety of a noninvasive, home‐based RF device applied for facial rejuvenation in Chinese people. Methods: A single‐center, open‐label, intraindividual controlled trial was performed on subjects who received an 8‐week treatment of the RF device. A total of 22 female individuals aged 25–60 years with Fitzpatrick skin type III–IV were enrolled. Efficacy of treatment was subjectively evaluated using the Fitzpatrick Wrinkle Classification Scale (FWCS) assessed by physician or overall satisfaction of subject with a 10‐point VAS, and objectively using the skin ultrasound examination as well as the 3D skin analysis system. Adverse event was recorded at each visit. Results: In comparison with the baseline, evaluator‐assessed FWCS scores showed significant improvement at 4 weeks (p < 0.005) and 8 weeks (p < 0.005) after treatment. All subjects reported different degrees of improvement in facial wrinkles after 8 weeks of treatment. The results of skin ultrasound examination revealed significant increase of the dermal thickness at week 8 (p < 0.05) as compared to the baseline. In addition, a significant decrease in the proportion and density of perioral wrinkles evaluated by the 3D skin analysis system was observed from baseline to week 4. The treatment was well‐tolerated, and no serious adverse event was observed. Conclusion: This noninvasive, home‐based RF device was effective in improving skin texture and elasticity with a safe and well‐tolerated treating procedure. [ABSTRACT FROM AUTHOR]

Abstract: Malignant glioma is one of the most challenging central nervous system diseases to treat and has high rates of recurrence and mortality. Current therapies often fail to control tumor progression or improve patient survival. Marinobufagenin (MBG) is an endogenous mammalian cardiotonic steroid involved in sodium pump inhibition. Currently, various studies have indicated the potential of MBG in cancer treatments; however, the precise mechanisms are poorly understood. The functions of MBG were examined using colony formation, migration, cell cycle, and apoptosis assays in glioma cells. A mitochondrial membrane potential assay was performed to determine the mitochondrial transmembrane potential change, and cytochrome c release from mitochondria was assayed by fluorescence microscopy. An immunofluorescence assay was performed, and the nuclear translocation of NF‐κB in glioma cells was confirmed by confocal microscopy. Western blotting and RT‐qPCR were used to detect the protein and gene expression levels, respectively. In addition, transfection experiment of ATP1A1‐siRNA was further carried out to confirm the role of sodium pump α1 subunit in the anticancer effect of MBG in human glioma. The apoptosis‐promoting and anti‐inflammatory effects of MBG were further investigated, and the sodium pump α1 subunit and the ERK signaling pathway were found to be involved in the anticancer effect of MBG. The in vivo anticancer efficacy of MBG was also tested in xenografts in nude mice. Thus, therapies targeting the ERK signaling‐mediated mitochondrial apoptotic pathways regulated by MBG might represent potential treatments for human glioma, and this study could accelerate the finding of newer therapeutic approaches for malignant glioma treatment. [ABSTRACT FROM AUTHOR]

The rising climatic concerns force the conventional power system to minimise the gas emissions. Microgrid integrating with renewable energy plays a key role in utilising power systems in a more environment friendly way. Compared with single renewable energy system, the microgrid with multi‐energy systems is more attractive in practice. The schedule problem is considered to schedule wind power, combined heating and power generation (CHP), battery, and power grid in order to satisfy the electricity load and heat loads in the microgrid with the minimal cost in real time. Owing to the stochastic nature of wind power generation, it is a challenge to solve the multi‐energy scheduling problem when using the obtained real‐time information. In this study, the joint scheduling of the microgrid with multi‐energy systems is formulated as a rolling horizon Markov decision process (MDP). Moreover, then the rollout algorithm is applied to solve the problem in order to deal with the large state and decision space of MDP, which is caused by the increase of the number of CHPs. The feasible base policy needed in the rollout algorithm is constructed using a greedy algorithm. Numerical results demonstrate that the algorithm can achieve the requirement of real‐time scheduling effectively. [ABSTRACT FROM AUTHOR]

The performance of an X‐band flexible band‐filter on ultra‐thin liquid crystal polymer (LCP) substrate is investigated. The 50 µm‐thick LCP substrate is adopted to enhance the flexibility of circuits. For the purpose of fabrication by the conventional printed circuit board process, copper‐clad laminate with 18 µm thickness is selected. Excellent microwave transmission characterisation is demonstrated by measuring the microstrip line at flat and bending conditions. An X‐band interdigital bandpass filter based on a half‐wavelength microstrip line resonator is designed and fabricated for purpose of demonstration. The measured results at the flat condition show that the insertion loss is 2.1 dB at centre frequency of 9.4 GHz and the return loss is better than 20 dB at the designed band. The performance at the bending condition shows that the bending effect causes little deterioration to the performance at a different bending radius. [ABSTRACT FROM AUTHOR]

Summary: Black wolfberry (Lycium ruthenicum Murr.) contains various bioactive metabolites represented by flavonoids, which are quite different among production regions. However, the underlying regulation mechanism of flavonoid biosynthesis governing the bioactivity of black wolfberry remains unclear.Presently, we compared the bioactivity of black wolfberry from five production regions. Multi‐omics were performed to construct the regulation network associated with the fruit bioactivity. The detailed regulation mechanisms were identified using genetic and molecular methods.Typically, Qinghai (QH) fruit exhibited higher antioxidant and anti‐inflammatory activities. The higher medicinal activity of QH fruit was closely associated with the accumulation of eight flavonoids, especially Kaempferol‐3‐O‐rutinoside (K3R) and Quercetin‐3‐O‐rutinoside (rutin). Flavonoid biosynthesis was found to be more active in QH fruit, and the upregulation of LrFLS, LrCHS, LrF3H and LrCYP75B1 caused the accumulation of K3R and rutin, leading to high medicinal bioactivities of black wolfberry. Importantly, transcription factor LrMYB94 was found to regulate LrFLS, LrCHS and LrF3H, while LrWRKY32 directly triggered LrCYP75B1 expression. Moreover, LrMYB94 interacted with LrWRKY32 to promote LrWRKY32‐regulated LrCYP75B1 expression and rutin synthesis in black wolfberry. Transgenic black wolfberry overexpressing LrMYB94/LrWRKY32 contained higher levels of K3R and rutin, and exhibited high medicinal bioactivities. Importantly, the LrMYB94/LrWRKY32‐regulated flavonoid biosynthesis was light‐responsive, showing the importance of light intensity for the medicinal quality of black wolfberry.Overall, our results elucidated the regulation mechanisms of K3R and rutin synthesis, providing the basis for the genetic breeding of high‐quality black wolfberry. [ABSTRACT FROM AUTHOR]

Ginseng (Panax ginseng Meyer) has long been consumed as a medicinal or functional food in East Asia. It is available as dried white ginseng (WG) and steamed red ginseng (RG), which might differ in ginsenoside profiles. We compared ginsenoside types of RG and WG using UPLC‐MS/MS and evaluated how they biologically affected heart of healthy rats by recording electrocardiography, measuring biochemical indicators, analyzing cardiac tissue slides, and Ca2+ signaling pathways. About 25 and 29 ginsenosides were detected in WG and RG, respectively, and the total ginsenoside content of RG contained was nearly 1.8 times higher than that of WG. Among them, ginsenoside Rg4, ginsenoside Rg6, ginsenoside Rh4, ginsenoside Rk1, ginsenoside Rg5, and protopanaxadiol were detected only in RG, while 20(R)‐ginsenoside Rg2 was detected only in WG. Male SD rats treated by intraperitoneal injection of WG or RG extracts were similar to the control in terms of electrocardiography and heart histology, indicating that both may not significantly affect the rats' myocardial function. However, WG and RG may induce mild cardiac injury resulting in increased cardiac collagen and creatine kinase levels. In addition, upregulated p‐CaMKII and PPARδ and downregulated SERCA2a for WG and RG treatments were further associated with increased cardiac contractility. In general, RG had less effect on the heart of healthy rats than WG, which may be due to RG having a high proportion of low‐polar ginsenosides. [ABSTRACT FROM AUTHOR]

Objectives: Temozolomide (TMZ) is one of the most commonly used clinical drugs for glioblastoma (GBM) treatment, but its drug sensitivity needs to be improved. Gamabufotalin (CS‐6), the primary component of the traditional Chinese medicine "ChanSu," was shown to have strong anti‐cancer activity. However, more efforts should be directed towards reducing its toxicity or effective treatment doses. Methods: Target fishing experiment, Western blotting, PCR, confocal immunofluorescence and molecular cloning techniques were performed to search for possible downstream signalling pathways. In addition, GBM xenografts were used to further determine the potential molecular mechanisms of the synergistic effects of CS‐6 and TMZ in vivo. Results: Mechanistic research revealed a negative feedback loop between ATP1A3 and AQP4 through which CS‐6 inhibited GBM growth and mediated the synergistic treatment effect of CS‐6 and TMZ. In addition, by mutating potential amino acid residues of ATP1A3, which were predicted by modelling and docking to interact with CS‐6, we demonstrated that abrogating hydrogen bonding of the amino acid Thr794 interferes with the activation of ATP1A3 by CS‐6 and that the Thr794Ala mutation directly affects the synergistic treatment efficacy of CS‐6 and TMZ. Conclusions: As the main potential target of CS‐6, ATP1A3 activation critically depends on the hydrogen bonding of Thr794 with CS‐6. The combination of CS‐6 and TMZ could significantly reduce the therapeutic doses and promote the anti‐cancer efficacy of CS‐6/TMZ monotherapy. [ABSTRACT FROM AUTHOR]

Dianhong Black Tea, a fermented tea containing various bioactive ingredients, has been found to have a significant role in alleviating alcoholic liver injury (ALI). One of its main unique components, Dianhong Black Tea volatile substances (DBTVS), may have potential anti‐ALI effects. However, its effects and underlying molecular mechanisms are still unknown. In this study, we aimed to investigate the potential of DBTVS as an anti‐ALI agent using alcohol‐fed rats. We assessed the effect of DBTVS on ALI by analyzing serum transaminase and lipid levels, as well as conducting hematoxylin–eosin and oil red O staining. Additionally, GC‐MS was used to detect the components of DBTVS, while transcriptome, proteomics analysis, Western blot, and molecular docking were employed to uncover the underlying mechanisms. Our results demonstrated that DBTVS significantly reduced serum ALT and AST levels and improved lipid metabolism disorders. Moreover, we identified 14 components in DBTVS, with five of them exhibiting strong binding affinity with key proteins. These findings suggested that DBTVS could be a promising agent for the prevention and treatment of ALI. Its potential therapeutic effects may be attributed to its ability to regulate lipid metabolism through the PPAR signaling pathway. [ABSTRACT FROM AUTHOR]

Isoalantolactone (IATL), a sesquiterpene lactone compound, possesses many pharmacological and biological activities, but its role in glioblastoma (GBM) treatment is still unknown. The aim of the current study was to investigate the antiglioma effects of IATL and to explore the underlying molecular mechanisms. In the current study, the biological functions of IATL were examined by MTT, cell migration, colony formation, and cell apoptosis assays. Confocal immunofluorescence techniques, chromatin immunoprecipitation, and pull‐down assays were used to explore the precise underlying molecular mechanisms. To examine IATL activity and the molecular mechanisms by which it inhibits glioma growth in vivo, we used a xenograft tumor mouse model. Furthermore, Western blotting was used to confirm the changes in protein expression after IATL treatment. According to the results, IATL inhibited IKKβ phosphorylation, thus inhibiting both the binding of NF‐κB to the cyclooxygenase 2 (COX‐2) promoter and the recruitment of p300 and eventually inhibiting COX‐2 expression. In addition, IATL induced glioma cell apoptosis by promoting the conversion of F‐actin to G‐actin, which in turn activates the cytochrome c (Cyt c) and caspase‐dependent apoptotic pathways. In the animal experiments, IATL reduced the size and weight of glioma tumors in xenograft mice and inhibited the expression of COX‐2 and phosphorylated NF‐κB p65 in the transplanted tumors. In conclusion, the current study indicated that IATL inhibited the expression of COX‐2 through the NF‐κB signaling pathway and induced the apoptosis of glioma cells by increasing actin transformation. These results suggested that IATL could be greatly effective in GBM treatment. [ABSTRACT FROM AUTHOR]

In the aorta of mid‐gestational mouse embryos, a specialized endothelial subpopulation termed hemogenic endothelial cells (HECs) develops into hematopoietic stem and progenitor cells (HSPCs), through a conserved process of endothelial‐to‐hematopoietic transition (EHT). EHT is tightly controlled by multiple intrinsic and extrinsic mechanisms. Nevertheless, the molecular regulators restraining this process remain poorly understood. Here, it is uncovered that, one of the previously identified HEC signature genes, Nupr1, negatively regulates the EHT process. Nupr1 deletion in endothelial cells results in increased HSPC generation in the aorta‐gonad‐mesonephros region. Furthermore, single‐cell transcriptomics combined with serial functional assays reveals that loss of Nupr1 promotes the EHT process by promoting the specification of hematopoiesis‐primed functional HECs and strengthening their subsequent hematopoietic differentiation potential toward HSPCs. This study further finds that the proinflammatory cytokine, tumor necrosis factor α (TNF‐α), is significantly upregulated in Nupr1‐deficient HECs, and the use of a specific TNF‐α neutralizing antibody partially reduces excessive HSPC generation in the explant cultures from Nupr1‐deficient embryos. This study identifies a novel negative regulator of EHT and the findings indicate that Nupr1 is a new potential target for future hematopoietic stem cell regeneration research. [ABSTRACT FROM AUTHOR]

The cover image is based on the Original Article Ginseng in white and red processed forms: Ginsenosides and cardiac side effects by Jiexin Zhou et al., https://doi.org/10.1002/fsn3.3879.By Jiexin Zhou; Jiarui Zhang; Pu Jing; Yu Lan; Xiaonian Cao; Huafang Feng; Xiaogang Liu and Qingqing LiuReported by Author; Author; Author; Author; Author; Author; Author; Author [Extracted from the article]

Characterization of functional T cell clusters is key to developing strategies for immunotherapy and predicting clinical responses in leukemia. Here, single‐cell RNA sequencing is performed with T cells sorted from the peripheral blood of healthy individuals and patients with B cell‐acute lymphoblastic leukemia (B‐ALL). Unbiased bioinformatics analysis enabled the authors to identify 13 T cell clusters in the patients based on their molecular properties. All 11 major T cell subsets in healthy individuals are found in the patients with B‐ALL, with the counterparts in the patients universally showing more activated characteristics. Two exhausted T cell populations, characterized by up‐regulation of TIGIT, PDCD1, HLADRA, LAG3, and CTLA4 are specifically discovered in B‐ALL patients. Of note, these exhausted T cells possess remarkable heterogeneity, and ten sub‐clusters are further identified, which are characterized by different cell cycle phases, naïve states, and GNLY (coding granulysin) expression. Coupled with single‐cell T cell receptor repertoire profiling, diverse originations of the exhausted T cells in B‐ALL are suggested, and clonally expanded exhausted T cells are likely to originate from CD8+ effector memory/terminal effector cells. Together, these data provide for the first‐time valuable insights for understanding exhausted T cell populations in leukemia. [ABSTRACT FROM AUTHOR]

Aims: We aimed to investigate the effect of different pulse numbers of high‐frequency repetitive transcranial magnetic stimulation (rTMS) over the motor cortex on cortical excitability in healthy participants. Methods: Fifteen healthy participants received 600 and 1200 pulses of 5‐Hz rTMS on separate days in a random order. Stimulation (duration, 2 seconds and interval, 1 seconds) was delivered over the left primary motor cortex for the hand, at 90% of resting motor threshold (rMT). The rMT and motor evoked potential (MEP) were measured before stimulation, and at 0 and 30 minutes after rTMS. Results: No significant differences were observed between the two conditions for MEP (P = .919) or rMT (P = .266). Compared with baseline, MEP was increased significantly at 0 (P < .001) and 30 minutes (P < .001) after stimulation. After stimulation, rMT was decreased at 0 minute for the 600 and 1200 pulse conditions (P < .001), but had recovered by 30 minutes (P = .073). Conclusion: Subthreshold 5‐Hz rTMS increased motor cortex excitability in healthy humans. However, the number of pulses may exhibit a ceiling effect in that beyond a certain point, that is, increasing the number of pulses may exhibit no further increase in cortical excitability. [ABSTRACT FROM AUTHOR]

A triple band‐notched UWB monopole antennas is presented for flexible electronics. To enhance the flexibility, ultra‐thin liquid crystal polymer with 50 μm thickness is used as the substrate. The antennas are constituted by swallow tail radiation patch and trapezoid ground. Moreover, band‐notched characteristic is realised by etching different sized elliptic single complementary split‐ring resonators on the radiation patch. An improved triple band‐notched UWB antenna with notched‐frequency bands at 3.7–4.2 GHz, 5.15–5.35 GHz, and 5.725–5.825 GHz are designed by a novel capacitance compensation method. The measured radiation patterns indicate that the antennas are an omni‐directional antenna both at flat and bent circumstances. The occupied area of antenna is 27 × 21 mm. [ABSTRACT FROM AUTHOR]