Operative treatment of cystic prolactinomas: a retrospective study.

BACKGROUND: The optimal therapeutic approach for cystic prolactinomas remains unclear. This study aimed to evaluate the remission rates of prolactinoma patients after surgical treatment and the risk factors affecting postoperative remission in cystic prolactinoma patients. METHODS: The clinical data were retrospectively compiled from 141 patients with prolactinomas (including 41 cases of cystic prolactinomas, 21 cases of solid microprolactinomas and 79 cases of solid macroprolactinomas) who underwent transsphenoidal surgery (TSS) between April 2013 and October 2021 at the First Affiliated Hospital of Sun Yat-sen University. RESULTS: Early postoperative remission was achieved in 65.83% (n = 27/41) of cystic prolactinomas, 80.95% (n = 17/21) of solid microprolactinomas and 40.51% (n = 32/79) of solid macroprolactinomas. The mean length of follow up in all patients was 43.95 ± 2.33 months (range: 6-105 months). The follow-up remission rates were 58.54%, 71.43% and 44.30% in cystic, solid micro- and solid macroprolactinomas, respectively. For cystic prolactinomas, the early postoperative remission rates in the patients with preoperative dopamine agonists (DA) treatment were significantly higher than those without preoperative DA treatment (p = 0.033), but the difference in the follow-up remission rates between these two groups was not significant (p = 0.209). Multivariate stepwise logistic regression analysis indicated that tumor size and preoperative prolactin (PRL) levels < 200 ng/ml were independent predictors for early postoperative remission in cystic prolactinomas. CONCLUSION: For cystic prolactinomas, tumor size and preoperative PRL levels were independent predictors of early postoperative remission. Preoperative DA therapy combined with TSS may be more beneficial to cystic prolactinoma patients.

Ticagrelor is related to nuisance bleeding after flow diversion of unruptured intracranial aneurysms.

Nuisance bleeding (NB) without urgent medical attention is rarely characterized despite its frequent occurrence in patients with cerebral aneurysms undergoing flow diversion (FD) who are maintained on dual antiplatelet therapy (DAPT). This study explored the risk factors for NB. Patients with unruptured cerebral aneurysms who underwent intervention using FD (July 2018 to May 2022) and had follow-up data were enrolled. Patient demographics, clinical characteristics, aneurysm features and follow-up data were analysed. Bleeding complications were classified as NB, internal bleeding and alarming bleeding. NB was characterized by easy bruising, bleeding from small cuts and nonfatal petechiae and ecchymosis. Univariate and multivariate logistic regression analyses were performed to determine risk factors for NB. This study assessed 121 patients. Of these, 52 (43.0%) patients had NB. Compared with the non-bleeding group, the NB group had more females (82.7% vs. 56.5%; p = 0.003), lower smoking rate (7.7% vs. 23.2%; p = 0.027) and smaller aneurysms (6.65 mm [4.60-9.60 mm] vs. 8.82 mm [5.65-15.65 mm]; p = 0.007) and had more patients maintained on ticagrelor-containing DAPT regimen (90.4% vs. 66.7%; p = 0.002). Multivariate logistic regression revealed that ticagrelor-containing DAPT regimen (odds ratio, 3.91; 95% confidence interval, 1.29-11.87; p = 0.016) was associated with NB. These results suggest that NB is a common bleeding complaint in patients on DAPT. In patients undergoing FD, DAPT with ticagrelor was the only independent risk factor for NB.

Analysis of expression profiles and bioinformatics suggests that plasma exosomal circular RNAs may be involved in ischemic stroke in the Chinese Han population.

Circular RNAs (circRNAs) have been confirmed to be associated with ischemic stroke(IS), but the involvement of exosomal circRNAs in plasma still needs to be extensively discussed. Therefore, we aimed to investigate the expression profile of exosomal circRNAs in plasma and the potential roles and mechanisms of exosomal circRNAs in the pathogenesis of ischemic stroke in the Chinese Han population. In this study, the plasma exosomal circRNA expression profiles of three IS patients and three healthy controls were analyzed using circRNA sequencing. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and circRNA-miRNA-mRNA regulatory network analysis were performed for the aberrantly expressed genes. Protein-protein interaction (PPI) networks and molecular complex detection algorithms (MCODEs) were analyzed by STRING and Cystoscope for functional annotation and construction, respectively. RNA-Seq analysis revealed that a total of 3540 circRNAs were aberrantly expressed in exosomes, 1177 circRNAs were significantly upregulated, and 2363 circRNAs were downregulated in IS patients compared to healthy controls. Bioinformatics analysis revealed that the parental genes of differentially expressed circRNAs as well as the mRNAs predicted in the circRNA-miRNA-mRNA regulatory network are enriched for signaling pathways associated with IS pathology, such as the MAPK signaling pathway, lipid and atherosclerosis, neurotrophic factor signaling pathways, mTOR signaling pathway, the p53 signaling pathway etc. Then, 10 hub genes were identified from the PPI and module networks, including FBXW11, FBXW7, UBE2V2, ANAPC7, CDC27, UBC, CDC5L, POLR2H, POLR2F and RBX1. Overall, the present study provides evidence of an altered plasma exosomal circRNA expression profile and its potential function in IS. Our findings may contribute to the study of the pathogenesis of circRNAs in IS and provide ideas for studying potential diagnostic biomarkers and therapeutic targets for IS.

NAL8 encodes a prohibitin that contributes to leaf and spikelet development by regulating mitochondria and chloroplasts stability in rice.

BACKGROUND: Leaf morphology and spikelet number are two important traits associated with grain yield. To understand how genes coordinating with sink and sources of cereal crops is important for grain yield improvement guidance. Although many researches focus on leaf morphology or grain number in rice, the regulating molecular mechanisms are still unclear. RESULTS: In this study, we identified a prohibitin complex 2α subunit, NAL8, that contributes to multiple developmental process and is required for normal leaf width and spikelet number at the reproductive stage in rice. These results were consistent with the ubiquitous expression pattern of NAL8 gene. We used genetic complementation, CRISPR/Cas9 gene editing system, RNAi gene silenced system and overexpressing system to generate transgenic plants for confirming the fuctions of NAL8. Mutation of NAL8 causes a reduction in the number of plastoglobules and shrunken thylakoids in chloroplasts, resulting in reduced cell division. In addition, the auxin levels in nal8 mutants are higher than in TQ, while the cytokinin levels are lower than in TQ. Moreover, RNA-sequencing and proteomics analysis shows that NAL8 is involved in multiple hormone signaling pathways as well as photosynthesis in chloroplasts and respiration in mitochondria. CONCLUSIONS: Our findings provide new insights into the way that NAL8 functions as a molecular chaperone in regulating plant leaf morphology and spikelet number through its effects on mitochondria and chloroplasts associated with cell division.

[Knowledge, attitude and practice of salt reduction among residents in four counties of Shandong and Jiangsu Provinces in 2013].

OBJECTIVE: To explore current status of knowledge, attitude and practice of salt reduction among adults in four counties of Shandong and Jiangsu Provinces, and analyze the relevant influencing factors. METHODS: In 2013, multi-stage cluster sampling was used to select the adults(aged 18-69) in Gaomi City of Weifang City and Fushan Distract of Yantai City, Shandong Province, and Xinyi City of Xuzhou City and Ganyu County of Lianyungang City, Jiangsu Province. A total of 9573 subjects were included. Knowledge, attitude and practice of anti-hypertension by low salt was collected using questionnaire and physical examination was conducted. Then the level of knowledge, attitude and practice of salt reduction was calculated, and multivariate Logistic regression model was used to analyze the influencing factors. RESULTS: A total of 3214 people had hypertension(33.57%), and the proportion of overweight and obesity was 36.20% and 19.48%, respectively. The awareness rate of salt reduction knowledge was between 22.50% and 51.35%; the attitude of salt reduction was between 82.24% and 93.01%, and the rate of salt reduction was between 10.86% and 46.16%. According to Logistic analysis, the degree of education had the greatest impact on knowledge(junior high school vs. elementary school and below: OR=2.30, 95%CI 2.06-2.57, high school and above vs. elementary school and below: OR=5.00, 95%CI 4.35-5.76). The knowledge level had the greatest impact on attitude(OR=3.10, 95%CI 2.80-3.43) and practice(OR=4.66, 95%CI 4.29-5.07). Those aged 45-69 years old had lower knowledge level(OR=0.64, 95%CI 0.58-0.71) but higher practice(OR=1.18, 95%CI 1.09-1.29). The knowledge(OR=3.66, 95%CI 3.34-4.01) and attitude(OR=1.84, 95%CI 1.69-2.02) of salt reduction among residents in Shandong were higher than those in Jiangsu. CONCLUSION: The awareness rate of knowledge is lower, the attitude support rate is higher, and the practice rate is lower among residents in Shandong and Jiangsu Provinces. More attention should be paid to the practical application of salt reduction.

[Method for continuous measurement of personal exposure to fine particulate matter].

OBJECTIVE: To develop a new accurate method for continuous measurement of personal exposure to fine particulate matter( PM_(2. 5) ) by integrating the advantage of both light scattering and gravimetric method. METHODS: The PM_(2. 5) concentrations were measured by both light scattering and gravimetric method simultaneously. The ratio of time-weighted average concentrations from gravimetric method to the responding values from light scattering method was calculated as coefficient of correction and used to calibrate the real-time PM_(2. 5) concentrations from light scattering method. RESULTS: The limit of detections( LOD) for 3, 10, 30 and 60 min time-weighted average concentrations of PM_(2. 5) were 4. 6, 4. 0, 3. 9 and 3. 7 µg/m~3, respectively. The precision( relativestandard deviation, RSD) was from 2. 1% to 9. 5%. The 30 min time-weighted average concentrations from this method were highly related to the results from TEOM method which was considered as reference method( Pearson r = 0. 934, P < 0. 001, n = 233), and no significantly bias between these two methods was detected by paired t test( P =0. 957). Zero drift was detected for 3 out of 10 devices with drift values in the range of- 5-- 3 µg/m~3 in the experiment of continuous 24 h monitoring conducted in the lab. And zero shift was also investigated in 7. 5%( 31 /412) field monitoring events, but most of the values shifted were within the range of- 3- 3 µg/m~3. The direction and scale of zero shift were not influenced by PM_(2. 5) concentrations. CONCLUSION: The developed method in this study that combines the advantages of both light-scattering and gravimetric method is validated to measure real-time concentrations of personal exposure to PM_(2. 5) .

Screening Efficient C-N Coupling Catalysts for Electrosynthesis of Acetamide and Output Ammonia through a Cascade Strategy of Electrochemical CO2 and N2 Reduction Using Cu-Based Nitrogen-Carbon Nanosheets.

Due to the limitation of the high-value-added products obtained from electrocatalytic CO2 reduction within an acid environment, introducing additional elements can expand the diversity of the products obtained during the CO2 reduction reaction (CO2RR) and nitrogen reduction reaction (NRR). Thus, coelectroreduction of CO2 and N2 is a new strategy for producing acetamide (CH3CONH2) via both C-C and C-N bond coupling using Cu-based nitrogen-carbon nanosheets. CO2 can reduce to CO, and a key ketene (*C═C═O) can be generated from *CO*CO dimerization; this ketene is postulated as an intermediate in the formation of acetamide. However, most studies focus on promoting the C-C bond formation. Here, we propose that C-N bond coupling can form acetamide through the interaction of *C═C═O with NH3. The acetamide is formed via a nucleophilic attack between *NH3 and the *C═C═O intermediate. The C-N coupling mechanism was successfully applied to expand the variety of nitrogen-containing products obtained from CO2 and N2 coreduction. Thus, we successfully screened Cu2-based graphite and Cu-based C3N4 as catalysts that can produce C2+ compounds by integrating CO dimerization with acetamide synthesis. In addition, we observed that Cu2-based C2N and Cu-based C3N4 catalysts are suitable for the NRR. Cu-based C3N4 showed high CO2RR and NRR activities with small negative limiting potential (UL) values of -0.83 and -0.58 V compared to those of other candidates, respectively. The formation of *COHCOH from *COHCO was considered the rate-determining step (RDS) during acetamide electrosynthesis. The limiting potential value of Cu2-based C2N was only -0.46 V for NH3 synthesis, and the formation of *NNH was via the RDS via an alternating path. The adsorption energy difference analysis both CO2 and N2 compare with the hydrogen evolution reaction (HER), suggesting that Cu2-based C2N exhibited the highest CO2RR and NRR selectivity among the 13 analyzed catalysts. The results of this study provide innovative insights into the design principle of Cu-based nitrogen-carbon electrocatalysts for generating highly efficient C-N coupling products.

Augmented reality technology shortens aneurysm surgery learning curve for residents.

OBJECTIVES: We aimed to prospectively investigate the benefit of using augmented reality (AR) for surgery residents learning aneurysm surgery. MATERIALS AND METHODS: Eight residents were included, and divided into an AR group and a control group (4 in each group). Both groups were asked to locate an aneurysm with a blue circle on the same screenshot after their viewing of surgery videos from both AR and non-AR tests. Only the AR group was allowed to inspect and manipulate an AR holographic representation of the aneurysm in AR tests. The actual location of the aneurysm was defined by a yellow circle by an attending physician after each test. Localization deviation was determined by the distance between the blue and yellow circle. RESULTS: Localization deviation was lower in the AR group than in the control group in the last 2 tests (AR Test 2: 2.7 ± 1.0 mm vs. 5.8 ± 4.1 mm, p = 0.01, non-AR Test 2: 2.1 ± 0.8 mm vs. 5.9 ± 5.8 mm, p < 0.001). The mean deviation was lower in non-AR Test 2 as compared to non-AR Test 1 in both groups (AR: p < 0.001, control: p = 0.391). The localization deviation of the AR group decreased from 8.1 ± 3.8 mm in Test 2 to 2.7 ± 1.0 mm in AR Test 2 (p < 0.001). CONCLUSION: AR technology provides an effective and interactive way for neurosurgery training, and shortens the learning curve for residents in aneurysm surgery.

Mapping cell diversity in human sporadic cerebral cavernous malformations.

BACKGROUND: Cerebral cavernous malformation (CCM) is a low-flow, bleeding-prone vascular disease that can cause cerebral hemorrhage, seizure and neurological deficits. Its inheritance mode includes sporadic or autosomal dominant inheritance with incomplete penetrance, namely sporadic CCM (SCCM) and familial CCM. SCCM is featured by single lesion and single affection in a family. Among CCM patients especially SCCM, the pathogenesis of the corresponding phenotypes and pathological features or candidate genes have not been fully elucidated yet. METHODS: Here, we performed in-depth single-cell RNA sequencing (scRNA-Seq) and bulk assay for transposase-accessible chromatin sequencing (ATAC-Seq) in SCCM and control patients. Further validation was conducted for the gene of interest using qPCR and RNA in situ hybridization (RNA FISH) techniques to provide further atlas and evidence for SCCM generative process. RESULTS: We identified six cell types in the SCCM and control vessels and found that the expression of NEK1, RNPC3, FBRSL1, IQGAP2, MCUB, AP3B1, ESCO1, MYO9B and PVT1 were up-regulated in SCCM tissues. Among the six cell types, we found that compared with control conditions, PVT1 showed a rising peak which followed the pseudo-time axis in endothelial cell clusters of SCCM samples, while showed an increasing trend in smooth muscle cell clusters of SCCM samples. Further experiments indicated that, compared with the control vessels, PVT1 exhibited significantly elevated expression in SCCM samples. CONCLUSION: In SCCM conditions, We found that in the process of development from control to lesion conditions, PVT1 showed a rising peak in endothelial cells and showed an increasing trend in smooth muscle cells at the same time. Overall, there was a significantly elevated expression of NEK1, RNPC3, FBRSL1, IQGAP2, MCUB, AP3B1, ESCO1, MYO9B and PVT1 in SCCM specimens compared to control samples.

Dilute Aqueous-Aprotic Electrolyte Towards Robust Zn-Ion Hybrid Supercapacitor with High Operation Voltage and Long Lifespan.

With the merits of the high energy density of batteries and power density of supercapacitors, the aqueous Zn-ion hybrid supercapacitors emerge as a promising candidate for applications where both rapid energy delivery and moderate energy storage are required. However, the narrow electrochemical window of aqueous electrolytes induces severe side reactions on the Zn metal anode and shortens its lifespan. It also limits the operation voltage and energy density of the Zn-ion hybrid supercapacitors. Using 'water in salt' electrolytes can effectively broaden their electrochemical windows, but this is at the expense of high cost, low ionic conductivity, and narrow temperature compatibility, compromising the electrochemical performance of the Zn-ion hybrid supercapacitors. Thus, designing a new electrolyte to balance these factors towards high-performance Zn-ion hybrid supercapacitors is urgent and necessary. We developed a dilute water/acetonitrile electrolyte (0.5 m Zn(CF3SO3)2 + 1 m LiTFSI-H2O/AN) for Zn-ion hybrid supercapacitors, which simultaneously exhibited expanded electrochemical window, decent ionic conductivity, and broad temperature compatibility. In this electrolyte, the hydration shells and hydrogen bonds are significantly modulated by the acetonitrile and TFSI- anions. As a result, a Zn-ion hybrid supercapacitor with such an electrolyte demonstrates a high operating voltage up to 2.2 V and long lifespan beyond 120,000 cycles.

Safety and efficacy of the flow diverter device for treating middle cerebral artery aneurysms of the proximal (M1) segment related to the lenticulostriate arteries: A single-center experience.

BACKGROUND: Experience using flow diverter devices (FDDs) to treat proximal (M1) middle cerebral artery aneurysms associated with the lenticulostriate artery (M1A-LA) remains limited. This study aimed to examine the efficacy and safety of an FDD to manage M1A-LA. METHOD: Patients with M1A-LA who received FDD treatment at a single center were included in the analysis. Data on the baseline characteristics, postoperative conditions, and follow-up results of the participants were recorded and analyzed. The aneurysms were categorized into three subtypes based on morphology and location. Aneurysms confined to the M1 segment were categorized as subtype A. Those extending to the M2 segment were classified as subtype B. Aneurysms designated as subtype C were confined to the M1 segment but with another independent aneurysm in the distal artery and the presence of healthy vessels between the two. Subgroup analyses were conducted on these subtypes and aneurysm sizes. To assess the consistency of follow-up results, Cronbach's kappa/alpha was used to calculate inter-rater variability. Somers's D coefficient was used to assess the correlation between each subgroup and the imaging outcomes; Fisher's exact test was used to compare the variability among the subgroups. RESULT: The cohort comprised 11 patients. Their Modified Rankin Scale scores between the perioperative and follow-up periods did not differ. During the follow-up period, four patients had completely occluded aneurysms, and five patients had partial occlusions. The remaining patients did not present with changes in their aneurysms. The kappa coefficient was 0.864 (p < 0.001). M1A-LA was divided into subtypes A, B, and C. Subtype A (defined as an aneurysm completely located in the M1 segment) had a higher complete occlusion rate than that of subtypes B and C, Somers's D R/C correlation coefficient was 0.553, with a 95% confidence interval of 0.1229-0.9823 (p = 0.009). The radiographic follow-up findings were not significantly correlated with the size of the aneurysm (p = 0.121) or the use of coiling (p = 0.903). No significant differences in subtypes (p = 0.264), aneurysm size (p = 0.657), or coiling use (p > 0.999) were observed. CONCLUSION: FDDs were safe and possibly effective against M1A-LA. However, they were not as effective as for intracranial aneurysms in other locations. FDDs are a satisfactory treatment option for M1A-LA, particularly for subtype A aneurysms.

Dysfunction of duplicated pair rice histone acetyltransferases causes segregation distortion and an interspecific reproductive barrier.

Postzygotic reproductive isolation, which results in the irreversible divergence of species, is commonly accompanied by hybrid sterility, necrosis/weakness, or lethality in the F1 or other offspring generations. Here we show that the loss of function of HWS1 and HWS2, a couple of duplicated paralogs, together confer complete interspecific incompatibility between Asian and African rice. Both of these non-Mendelian determinants encode the putative Esa1-associated factor 6 (EAF6) protein, which functions as a characteristic subunit of the histone H4 acetyltransferase complex regulating transcriptional activation via genome-wide histone modification. The proliferating tapetum and inappropriate polar nuclei arrangement cause defective pollen and seeds in F2 hybrid offspring due to the recombinant HWS1/2-mediated misregulation of vitamin (biotin and thiamine) metabolism and lipid synthesis. Evolutionary analysis of HWS1/2 suggests that this gene pair has undergone incomplete lineage sorting (ILS) and multiple gene duplication events during speciation. Our findings have not only uncovered a pair of speciation genes that control hybrid breakdown but also illustrate a passive mechanism that could be scaled up and used in the guidance and optimization of hybrid breeding applications for distant hybridization.

The structural basis of conserved residue variant effect on enzyme activity of UGT2B15.

UDP-glucuronosyltransferase 2B15 (UGT2B15) is a crucial phase II drug-metabolizing enzyme, which glucuronidates various compounds, including clinical drugs and hormones. Mutants might affect glucuronidation, leading to a disruption of drug metabolism in vivo and decrease of therapeutic effect. Here, we mainly analyzed two representative mutants, H401P and L446S, on UGT2B15 activity using glucuronidation assays, molecular dynamic (MD) simulation and X-ray diffraction methods. The enzyme activity of L446S obviously increased six-fold than the wild type, although the enzyme activities of P191L, T374A, and H401P were lost apparently. Furthermore, we used MD simulations to calculate the energy change in the catalytic process of H401P and L446S, and the results indicated the free binding energies of H401P mutant to oxazepam and UDPGA were -30.98 ± 1.00 kcal/mol and -36.42 ± 1.04 kcal/mol, respectively, increased obviously compared to wild type, suggesting the mutation on position 401 had a crucial effect on the catalysis. Moreover, the three-dimensional structure of UGT2B15 C-terminal domain L446S was determined through protein crystallography and X-ray diffraction technology and the results suggested that one more hydrogen bonding between S446 and K410 was formed in the S446 crystal structure, compared to the wild type. Isothermal titration calorimetry assay further revealed the Kd values of C-terminal domain of UGT2B15 harbored L446S towards the cofactor UDPGA was similar to the value of wild type. Above all, our results pointed out that H401P and L446S affected the enzyme activity by different mechanism. Our work provided a helpful mechanism for variance explained in the UGTs catalyzation process.

Risk Factors for Cerebral Infarction After Microsurgical Clipping of Hunt-Hess Grade 0-2 Single Intracranial Aneurysm: A Retrospective Study.

OBJECTIVE: The study aimed to explore risk factors for cerebral infarction after microsurgical clipping in patients with Hunt-Hess grade 0-2 single intracranial aneurysms. METHODS: A total of 137 patients with Hunt-Hess grade 0-2 single intracranial aneurysms treated with microsurgical clipping between March 2017 and December 2020 were retrospectively enrolled. Patients were divided into 2 groups on the basis of the occurrence of cerebral infarction after surgery. RESULTS: Of 137 enrolled patients, 14 (10.22%) showed cerebral infarction symptoms after surgery. Univariate analysis indicated that ruptured aneurysm status, aneurysm rupture during surgery, history of transient ischemic attack (TIA)/stroke, aneurysm size ≥7 mm, temporary clipping, intraoperative systolic hypotension (IOH), and occurrences of intraoperative motor-evoked potentials change were significantly related to postoperative cerebral infarction (PCI). However, using multivariate regression, only history of TIA/stroke (odds ratio = 0.124; 95% confidence interval [CI] = 0.021-0.748, P = 0.023) and IOH (odds ratio = 0.032; 95% CI = 0.005-0.210, P < 0.001) were independent predictors for PCI. Receiver operating characteristic curve analysis showed that the critical duration of temporary clipping and IOH that minimized the risk of PCI was 5.5 minutes and 7.5 minutes, respectively. CONCLUSIONS: Our study identified history of TIA/stroke and IOH as independent risk factors for cerebral infarction after microsurgical clipping.

Advances on Axial Coordination Design of Single-Atom Catalysts for Energy Electrocatalysis: A Review.

Single-atom catalysts (SACs) have garnered increasingly growing attention in renewable energy scenarios, especially in electrocatalysis due to their unique high efficiency of atom utilization and flexible electronic structure adjustability. The intensive efforts towards the rational design and synthesis of SACs with versatile local configurations have significantly accelerated the development of efficient and sustainable electrocatalysts for a wide range of electrochemical applications. As an emergent coordination avenue, intentionally breaking the planar symmetry of SACs by adding ligands in the axial direction of metal single atoms offers a novel approach for the tuning of both geometric and electronic structures, thereby enhancing electrocatalytic performance at active sites. In this review, we briefly outline the burgeoning research topic of axially coordinated SACs and provide a comprehensive summary of the recent advances in their synthetic strategies and electrocatalytic applications. Besides, the challenges and outlooks in this research field have also been emphasized. The present review provides an in-depth and comprehensive understanding of the axial coordination design of SACs, which could bring new perspectives and solutions for fine regulation of the electronic structures of SACs catering to high-performing energy electrocatalysis.

Pathway network-based quantitative modeling of the time-dependent and dose-response anti-inflammatory effect of Reduning Injection.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine (TCM) has extensive healing effects on inflammatory diseases with few side effects. Reduning injection (RDNI), a TCM prescription composed of Lonicera japonica Thunb., Gardenia jasminoides Ellis. and Artemisia annua L., is wildly used for treating inflammatory diseases. However, the mechanism of action of RDNI, like most TCM prescriptions, is unclear due to the complexity of relationships between components and their curative effects. AIM OF THE STUDY: To develop a universal systems pharmacology protocol for mechanism modeling of TCM and apply it to reveal the real-time anti-inflammatory effect of Reduning Injection. MATERIALS AND METHODS: Combined with database mining and references, a regulatory mechanism network of inflammation was constructed. A quantitative model was established afterwards by integrating pharmacokinetic data and two network parameters, namely Network Efficiency and Network Flux. The time-dependent and dose-response relationship of RDNI on the regulation of inflammation was then quantitatively evaluated. ELISA tests were performed to verify the reliability of the model. RESULTS: Three cytokines, namely IL-1ß, IL-6 and TNF-α were screened out to be markers for evaluation of the anti-inflammatory effect of RDNI. An HPLC method for the simultaneous determination of 10 RDNI compounds in SD rat plasma was established and then applied to pharmacokinetic studies. Based on compound activity and pharmacokinetic data, the time-dependent effect of RDNI were quantitatively predicted by the pathway network-based modeling procedure. CONCLUSIONS: The quantitative model established in this work was successfully applied to predict a TCM prescription's real-time dynamic healing effect after administration. It is qualified to provide novel insights into the time-dependent and dose-effect relationship of drugs in an intricate biological system and new strategies for investigating the detailed molecular mechanisms of TCM.

Integration of photovoltaic and photogating effects in a WSe2/WS2/p-Si dual junction photodetector featuring high-sensitivity and fast-response.

Two-dimensional (2D) material-based van der Waals (vdW) heterostructures with exotic semiconducting properties have shown tremendous potential in next-generation photovoltaic photodetectors. Nevertheless, these vdW heterostructure devices inevitably suffer from a compromise between high sensitivity and fast response. Herein, an ingenious photovoltaic photodetector based on a WSe2/WS2/p-Si dual-vdW heterojunction is demonstrated. First-principles calculations and energy band profiles consolidate that the photogating effect originating from the bottom vdW heterojunction not only strengthens the photovoltaic effect of the top vdW heterojunction, but also suppresses the recombination of photogenerated carriers. As a consequence, the separation of photogenerated carriers is facilitated and their lifetimes are extended, resulting in higher photoconductive gain. Coupled with these synergistic effects, this WSe2/WS2/p-Si device exhibits both high sensitivity (responsivity of 340 mA W-1, a light on/off ratio greater than 2500, and a detectivity of 3.34 × 1011 Jones) and fast response time (rise/decay time of 657/671 µs) under 405 nm light illumination in self-powered mode. Finally, high-resolution visible-light and near-infrared imaging capabilities are demonstrated by adopting this dual-heterojunction device as a single pixel, indicating its great application prospects in future optoelectronic systems.

Comprehensive Analysis of Blood-Based m6A Methylation in Human Ischemic Stroke.

Alterations of N6-methyladenosine (m6A) methylation have been reported in the cerebral cortices of mouse and rat models of ischemic stroke (IS). However, the role of m6A methylation in human IS is still unknown. We assessed m6A levels in peripheral blood from patients with IS and healthy controls. A transient middle cerebral artery occlusion and reperfusion (tMCAO/R) mouse model, and an oxygen-glucose deprivation/reperfusion (OGD/R) model in A172 cells were established to further assess m6A levels. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA sequencing were performed in the peripheral blood of patients with IS and healthy controls. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were used to identify underlying biological processes. In this study, we found that global m6A levels were elevated in the peripheral blood of patients with IS, in the cerebral cortex of mice after tMCAO/R treatment and in A172 cells after OGD/R treatment. MeRIP-seq analysis identified 2115 altered m6A peaks in patients with IS, 1052 upregulated and 1063 downregulated. Downregulated methylated mRNAs were enriched in Hippo signaling pathway, cytokine-cytokine receptor interaction, NF-kappa B signaling pathway, etc. Upregulated methylated mRNAs were enriched in calcium signaling pathways, Hedgehog signaling pathway, MAPK signaling pathway, etc. Moreover, a total of 84 differentially expressed mRNAs with altered m6A peaks were identified and enriched in EGFR tyrosine kinase inhibitor, Hematopoietic cell lineage, and cytokine-cytokine receptor interactions. This study is the first to profile the transcriptome-wide m6A methylome of peripheral blood in human IS and uncover increased global m6A levels in the peripheral blood of patients with IS.

FOXM1 maintains fatty acid homoeostasis through the SET7-H3K4me1-FASN axis.

Reprogramming of metabolic genes and subsequent alterations in metabolic phenotypes occur widely in malignant tumours, including glioblastoma (GBM). FOXM1 is a potent transcription factor that plays an oncogenic role by regulating the expression of many genes. As a SET domain containing protein, SET7 is a protein lysine methyltransferase which monomethylates histone proteins and other proteins. The epigenetic modification of histones regulates gene expressions by epigenetically modifying promoters of DNAs and inter vening in tumor development. Activation of FASN increased de novo fatty acid (FA) synthesis, a hallmark of cancer cells. Here, we report that FOXM1 may directly promote the transcription of SET7 and activate SET7-H3K4me1-FASN axis, which results in the maintenance of de novo FA synthesis.

SAD score of intracranial aneurysms for rupture risk assessment based on high-resolution vessel wall imaging.

OBJECTIVE: We aimed to develop a comprehensive model that integrates the radiological, morphological, and clinical factors to assess rupture risk for intracranial aneurysms. METHODS: We prospectively enrolled patients with intracranial saccular aneurysms who underwent high-resolution vessel wall imaging (HR-VWI) preoperatively. Clinical characteristics, aneurysm features and aneurysm wall enhancement scale (AWES) were recorded. AWES was categorized into three grades (no/faint/strong enhancement) by comparing AWE to enhancement of the pituitary infundibulum or choroid plexus on HR-VWI. Univariate and multivariate logistic regression analyses were performed to determine risk factors associated with aneurysmal rupture. RESULTS: A total of 25 ruptured and 116 unruptured aneurysms were included. Multivariate logistic regression analysis revealed that non-ICA site (OR 6.25, 95% CI 1.35-28.30, P = 0.019), AWES (OR 5.99, 95% CI 2.51-14.29, P < 0.001) and daughter sac or lobulated shape (OR 6.22, 95% CI 1.68-23.16, P = 0.006) were independent factors associated with ruptured aneurysms. The "SAD" model was generated and named after the first letters of each of these factors. SAD scores of 0-4 predicted 0, 2%, 12%, 42% and 100% ruptured aneurysms, respectively. The area under the receiver operating characteristic curve for the SAD model was 0.8822. CONCLUSION: The SAD model aids in distinguishing aneurysm rupture status and in managing unruptured aneurysms. Larger cohort studies are needed to confirm its applicability in predicting the rupture risk of unruptured aneurysms.