The rise of baobab trees in Madagascar.

The baobab trees (genus Adansonia) have attracted tremendous attention because of their striking shape and distinctive relationships with fauna1. These spectacular trees have also influenced human culture, inspiring innumerable arts, folklore and traditions. Here we sequenced genomes of all eight extant baobab species and argue that Madagascar should be considered the centre of origin for the extant lineages, a key issue in their evolutionary history2,3. Integrated genomic and ecological analyses revealed the reticulate evolution of baobabs, which eventually led to the species diversity seen today. Past population dynamics of Malagasy baobabs may have been influenced by both interspecific competition and the geological history of the island, especially changes in local sea levels. We propose that further attention should be paid to the conservation status of Malagasy baobabs, especially of Adansonia suarezensis and Adansonia grandidieri, and that intensive monitoring of populations of Adansonia za is required, given its propensity for negatively impacting the critically endangered Adansonia perrieri.

Targeting the forkhead box protein P1 pathway as a novel therapeutic approach for cardiovascular diseases.

Cardiovascular disease (CVD) is the leading cause of death worldwide and encompasses diverse diseases of the vasculature, myocardium, cardiac electrical circuit, and cardiac development. Forkhead box protein P1 (Foxp1) is a large multi-domain transcriptional regulator belonging to the Fox family with winged helix DNA-binding protein, which plays critical roles in cardiovascular homeostasis and disorders. The broad distribution of Foxp1 and alternative splicing isoforms implicate its distinct functions in diverse cardiac and vascular cells and tissue types. Foxp1 is essential for diverse biological processes and has been shown to regulate cellular proliferation, apoptosis, oxidative stress, fibrosis, angiogenesis, cardiovascular remodeling, and dysfunction. Notably, both loss-of-function and gain-of-function approaches have defined critical roles of Foxp1 in CVD. Genetic deletion of Foxp1 results in pathological cardiac remodeling, exacerbation of atherosclerotic lesion formation, prolonged occlusive thrombus formation, severe cardiac defects, and embryo death. In contrast, activation of Foxp1 performs a wide range of physiological effects, including cell growth, hypertrophy, differentiation, angiogenesis, and cardiac development. More importantly, Foxp1 exerts anti-inflammatory and anti-atherosclerotic effects in controlling coronary thrombus formation and myocardial infarction (MI). Thus, targeting for Foxp1 signaling has emerged as a pre-warning biomarker and a novel therapeutic approach against progression of CVD, and an increased understanding of cardiovascular actions of the Foxp1 signaling will help to develop effective interventions. In this review, we focus on the diverse actions and underlying mechanisms of Foxp1 highlighting its roles in CVD, including heart failure, MI, atherosclerosis, congenital heart defects, and atrial fibrillation.

Using pre-operative radiomics to predict microvascular invasion of hepatocellular carcinoma based on Gd-EOB-DTPA enhanced MRI.

OBJECTIVES: We aimed to investigate the value of performing gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) enhanced magnetic resonance imaging (MRI) radiomics for preoperative prediction of microvascular invasion (MVI) of hepatocellular carcinoma (HCC) based on multiple sequences. METHODS: We randomly allocated 165 patients with HCC who underwent partial hepatectomy to training and validation sets. Stepwise regression and the least absolute shrinkage and selection operator algorithm were used to select significant variables. A clinicoradiological model, radiomics model, and combined model were constructed using multivariate logistic regression. The performance of the models was evaluated, and a nomogram risk-prediction model was built based on the combined model. A concordance index and calibration curve were used to evaluate the discrimination and calibration of the nomogram model. RESULTS: The tumour margin, peritumoural hypointensity, and seven radiomics features were selected to build the combined model. The combined model outperformed the radiomics model and the clinicoradiological model and had the highest sensitivity (90.89%) in the validation set. The areas under the receiver operating characteristic curve were 0.826, 0.755, and 0.708 for the combined, radiomics, and clinicoradiological models, respectively. The nomogram model based on the combined model exhibited good discrimination (concordance index = 0.79) and calibration. CONCLUSIONS: The combined model based on radiomics features of Gd-EOB-DTPA enhanced MRI, tumour margin, and peritumoural hypointensity was valuable for predicting HCC microvascular invasion. The nomogram based on the combined model can intuitively show the probabilities of MVI.

Size selection and placement of pedicle screws using robot-assisted versus fluoroscopy-guided techniques for thoracolumbar fractures: possible implications for the screw loosening rate.

BACKGROUND: There has been increased development of robotic technologies for the accuracy of percutaneous pedicle screw placement. However, it remains unclear whether the robot really optimize the selection of screw sizes and enhance screw stability. The purpose of this study is to compare the sizes (diameter and length), placement accuracy and the loosening rate of pedicle screws using robotic-assisted versus conventional fluoroscopy approaches for thoracolumbar fractures. METHODS: A retrospective cohort study was conducted to evaluate 70 consecutive patients [34 cases of robot-assisted percutaneous pedicle screw fixation (RAF) and 36 of conventional fluoroscopy-guided percutaneous pedicle screw fixation (FGF)]. Demographics, clinical characteristics, and radiological features were recorded. Pedicle screw length, diameter, and pedicle screw placement accuracy were assessed. The patients' sagittal kyphosis Cobb angles (KCA), anterior vertebral height ratios (VHA), and screw loosening rate were evaluated by radiographic data 1 year after surgery. RESULTS: There was no significant difference in the mean computed tomography (CT) Hounsfield unit (HU) values, operation duration, or length of hospital stay between the groups. Compared with the FGF group, the RAF group had a lower fluoroscopy frequency [14 (12-18) vs. 21 (16-25), P < 0.001] and a higher "grade A + B" pedicle screw placement rate (96.5% vs. 89.4%, P < 0.05). The mean screw diameter was 6.04 ± 0.55 mm in the RAF group and 5.78 ± 0.50 mm in the FGF group (P < 0.001). The mean screw length was 50.45 ± 4.37 mm in the RAF group and 48.63 ± 3.86 mm in the FGF group (P < 0.001). The correction loss of the KCA and VHR of the RAF group was less than that of the FGT group at the 1-year follow-up [(3.8 ± 1.8° vs. 4.9 ± 4.2°) and (5.5 ± 4.9% vs. 6.4 ± 5.7%)], and screw loosening occurred in 2 out of 34 patients (5.9%) in the RAF group, and 6 out of 36 patients (16.7%) in the FGF group, but there were no significant differences (P > 0.05). CONCLUSION: Compared with the fluoroscopy-guided technique, robotic-assisted spine surgery decreased radiation exposure and optimizes screw trajectories and dimensions intraoperatively. Although not statistically significant, the loosening rate of the RAF group was lower that of than the FGT group.

Analysis of and Reduction in Noise in Current Measurement of XCP under the Laboratory Condition.

Expendable current profiler (XCP) is one of the most vital devices detecting ocean currents. Compared with other methods, the expendable feature makes trials with XCP much faster and more hidden, while the accuracy of XCP is considerably influenced by electromagnetic noise all around. Aiming at researching the influence and reducing the noise, this study carried out laboratory simulation experiments. The designed laboratory experiments mainly have a self-developed rotation gear, an XCP prototype, a plastic flume, and two copper plates as power. Firstly, these experiments analyzed the main sources of electromagnetic noise for XCP detection. Secondly, we built a noise simulation environment and conducted XCP detection experiments under different noise in the flume. The data obtained by XCP were transmitted to the computer to be stored and processed. The results show the internal noise impact on XCP is significantly less than the external. For an excitation power of 1 mV, the offset of theoretical and actual data brought by internal noise is 12 times smaller than external and can be corrected.

TRPC5 in cardiovascular diseases.

Cardiovascular diseases (CVD), especially acute myocardial infarction, are the leading cause of death, morbidity and disability across the world, affecting millions of people each year. Atherosclerosis (AS) is the major cause of CVD, and is a chronic inflammation involving different cell types and various molecular mechanisms. Ca2+ dynamics of endothelial cells (ECs) and smooth muscle cells (SMCs) exert a significant influence on many aspects of CVD. Transient receptor potential channel 5 (TRPC5) is a member of the transient receptor potential (TRP) channels, which consists of a large number of nonselective cation channels with variable degrees of Ca2+-permeability. As a Ca2+-permeable cation channel, Human TRPC5 is expressed in a number of cell types, including ECs and muscle cells, as well as lungs and kidneys. TRPC5 is involved in renal, tumorous, neuronal and vascular diseases. In recent years, the roles of TRPC5 in CVD have been widely implicated in various disorders, such as AS, cardiac hypertrophy and blood pressure regulation. The TRPC5 mechanism of action may be associated with regulation of calcium homeostasis, oxidative stress and apoptosis. In this review, we highlight the significant roles of TRPC5 in the heart, and evaluate the potential of therapeutics targets which block TRPC5 for the treatment of CVD and related diseases.

Carbon pools in China's terrestrial ecosystems: New estimates based on an intensive field survey.

China's terrestrial ecosystems have functioned as important carbon sinks. However, previous estimates of carbon budgets have included large uncertainties owing to the limitations of sample size, multiple data sources, and inconsistent methodologies. In this study, we conducted an intensive field campaign involving 14,371 field plots to investigate all sectors of carbon stocks in China's forests, shrublands, grasslands, and croplands to better estimate the regional and national carbon pools and to explore the biogeographical patterns and potential drivers of these pools. The total carbon pool in these four ecosystems was 79.24 ± 2.42 Pg C, of which 82.9% was stored in soil (to a depth of 1 m), 16.5% in biomass, and 0.60% in litter. Forests, shrublands, grasslands, and croplands contained 30.83 ± 1.57 Pg C, 6.69 ± 0.32 Pg C, 25.40 ± 1.49 Pg C, and 16.32 ± 0.41 Pg C, respectively. When all terrestrial ecosystems are taken into account, the country's total carbon pool is 89.27 ± 1.05 Pg C. The carbon density of the forests, shrublands, and grasslands exhibited a strong correlation with climate: it decreased with increasing temperature but increased with increasing precipitation. Our analysis also suggests a significant sequestration potential of 1.9-3.4 Pg C in forest biomass in the next 10-20 years assuming no removals, mainly because of forest growth. Our results update the estimates of carbon pools in China's terrestrial ecosystems based on direct field measurements, and these estimates are essential to the validation and parameterization of carbon models in China and globally.

Inhibition of NMDA Receptors Downregulates Astrocytic AQP4 to Suppress Seizures.

Aquaporin 4 (AQP4), a water-specific channel protein locating on the astrocyte membrane, has been found to be antagonist, agonist and undergone closely related to epilepsy. Our previous study showed that inhibition of an N-methyl-D-aspartate receptor (NMDAR) subunit NR2A can suppress epileptic seizures, suggesting that AQP4 is potentially involved in NR2A-mediated epilepsy treatment. In this study, we aimed to explore the relevance of AQP4 in NR2A-mediated seizures treatment in pentylenetetrazol (PTZ)-induced rat models. We performed electroencephalogram (EEG) recording and examined AQP4 expression at mRNA and protein levels, and the downstream molecules of AQP4 as well. It showed that AQP4 expression was increased after the induction of seizures. Lateral ventricle pretreatment of NR2A inhibitor could mitigate the PTZ-induced seizures severity and counterbalance the increase of AQP4 expression. In contrast, NR2A activator that resulted in seizures aggravation could further augment the seizure-related elevations of AQP4 expression. Pharmacological inhibition of AQP4 alone could also suppress the PTZ-induced seizure activities, with decreased expressions of NF-κB p65, interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-α in the brain. The results indicated that increased expression of AQP4 might be an important mechanism involved in NR2A of NMDAR-mediated treatment for epileptic seizures, enlightening a potentially new target for seizures treatment.

The Impacts of Soil Fertility and Salinity on Soil Nitrogen Dynamics Mediated by the Soil Microbial Community Beneath the Halophytic Shrub Tamarisk.

Nitrogen (N) is one of the most common limiting nutrients for primary production in terrestrial ecosystems. Soil microbes transform organic N into inorganic N, which is available to plants, but soil microbe activity in drylands is sometimes critically suppressed by environmental factors, such as low soil substrate availability or high salinity. Tamarisk (Tamarix spp.) is a halophytic shrub species that is widely distributed in the drylands of China; it produces litter enriched in nutrients and salts that are thought to increase soil fertility and salinity under its crown. To elucidate the effects of tamarisks on the soil microbial community, and thus N dynamics, by creating "islands of fertility" and "islands of salinity," we collected soil samples from under tamarisk crowns and adjacent barren areas at three habitats in the summer and fall. We analyzed soil physicochemical properties, inorganic N dynamics, and prokaryotic community abundance and composition. In soils sampled beneath tamarisks, the N mineralization rate was significantly higher, and the prokaryotic community structure was significantly different, from soils sampled in barren areas, irrespective of site and season. Tamarisks provided suitable nutrient conditions for one of the important decomposers in the area, Verrucomicrobia, by creating "islands of fertility," but provided unsuitable salinity conditions for other important decomposers, Flavobacteria, Gammaproteobacteria, and Deltaproteobacteria, by mitigating salt accumulation. However, the quantity of these decomposers tended to be higher beneath tamarisks, because they were relatively unaffected by the small salinity gradient created by the tamarisks, which may explain the higher N mineralization rate beneath tamarisks.

Comparison of Pediatric Forearm Fracture Fixation Between Single- and Double-Elastic Stable Intramedullary Nailing.

The purpose of this study was to evaluate and compare the outcome of single- and double-elastic stable intramedullary nailing (ESIN) for the treatment of pediatric both-bone forearm fractures. We retrospectively analyzed 49 children with both-bone forearm fractures treated with ESIN. Twenty-four patients were treated with single-ESIN (S-ESIN) to fixate the radius only, and the other 25 patients were treated with double-ESIN (D-ESIN) to fixate the radius and ulna. The duration of surgery, times of fluoroscopy, cost of hospitalization, period of castoff, union time, radiographic outcomes, clinical results, and postoperative complications were compared. The duration of surgery, times of fluoroscopy, and cost of hospitalization were significantly lower in the S-ESIN group; however, the average period of castoff was longer in the S-ESIN group. The incidence of delayed union of the ulna was significantly higher in the D-ESIN than in the S-ESIN group. Although the mean angulation deformity of the ulna in the S-ESIN group was significantly larger than in the D-ESIN group, both of them were acceptable (<10 degrees). Despite this, there was no difference in the loss of forearm motion and complication rates between the 2 groups. In conclusion, our data suggest that S-ESIN to fixate the radius alone remains an equally effective fixation method in the pediatric population compared with both-bone fixation and is our treatment of choice.

[Studies of Male Fertility with Raman Spectroscopy].

Raman spectroscopy which belongs to scattering spectroscopy obtained molecular vibrational and rotational information to achieve detection and analysis of molecular structure and corresponding changes through recording the frequency shift when light interacted with materials. Compared with routine biochemical analysis, Raman spectroscopy has the advantage of non-invasive, label-free and no sample requirement. Raman spectroscopy has been widely applied in biomedical field such as human tissue, organs, cells and human body fluids for disease diagnosis. This article mainly focuses on recent research advances of Raman spectroscopy in human semen. Firstly, Raman spectroscopy(including surface-enhanced Raman spectroscopy, SERS) employed in forensic science for semen analysis, and some related data processing methods were introduced, then Raman spectroscopy involved investigations of male fertility was highlighted, more specifically, the Raman-based qualitative and quantitative analysis which assist the objective detection and evaluation of male fertility. Furthermore, studies of single sperm cell based on micro-Raman system to characterize and evaluate sperm quality and the preliminarily obtained Raman biomarkers which indicate high-quality sperm cell were introduced. Finally, the potential development of Raman spectroscopy involved in reproduction and fertility field was also discussed.

Identification and Characterization of Three Monilinia Species from Plum in China.

In total, 112 Monilinia spp. single-spore isolates were collected from plum fruit (Prunus salicina) symptomatic for brown rot disease from Yunnan, Hubei, and Zhejiang provinces and Chongqing municipality, China between 2012 and 2014. Three distinct colony morphologies (phenotypes) were observed on potato dextrose agar and two isolates per phenotype were selected for further analysis. Colony color, colony shape, conidia size, number of germ tubes per conidia, and pathogenicity on plum were investigated. The ribosomal internal transcribed spacer regions 1 and 2 as well as a polymerase chain reaction-based method that amplified fragments of the glyceraldehyde-3-phosphate dehydrogenase (G3PDH) and ß-tubulin (TUB2) genes were used to identify the isolates to the species level. The three phenotypes were identified to be three different species: Monilinia fructicola, Monilia mumecola, and Monilia yunnanensis. Phylogenetic analysis based on G3PDH and TUB2 nucleotide sequences revealed that isolates within species clustered together regardless of host or geographical origin, suggesting that these factors did not play an important role for the evolutionary separation of the described species.

Effects of Rainfall Exclusion Treatment on Photosynthetic Characteristics of Black Locust in the Sub-Humid Region of the Loess Plateau, China.

The mesic-origin species Robinia pseudoacacia L. (black locust) is widely planted in the semiarid and sub-humid areas of the Loess Plateau for the reforestation of vegetation-degraded land. Under the scenario of changing precipitation patterns, exploring the response of photosynthesis to drought allows us to assess the risk to sustainable development of these plantations. In this study, paired plots were established including the control and a treatment of 30% exclusion of throughfall (since 2018). The photosynthetic characteristics were investigated using a portable photosynthesis system for four periods in the full-leaf growing season of 2021-2022, the fourth and fifth years, on both treated and controlled sampling trees. Leaf gas exchange parameters derived from diurnal changing patterns, light response curves, and CO2 response curves showed significant differences except for period II (9-11 September 2021) between the two plots. The photosynthetic midday depression was observed in 2022 in the treated plot. Meanwhile, the decline of net photosynthetic rate in the treated plot was converted from stomatal limitation to non-stomatal limitation. Furthermore, we observed that black locust adapted to long-term water deficiency by reducing stomatal conductance, increasing water use efficiency and intrinsic water use efficiency. The results demonstrate that reduction in precipitation would cause photosynthesis decrease, weaken the response sensitivity to light and CO2, and potentially impair photosynthetic resilience of the plantations. They also provide insights into the changes in photosynthetic functions under global climate change and a reference for management of plantations.

[Characteristics of soil moisture limitation and non-limitation in the response of sap flow to transpiration driving factors]. / æ ‘å¹²æ¶²æµå¯¹è’¸è ¾é©±åŠ¨å› å­å“åº”çš„åœŸå£¤æ°´åˆ†é™åˆ¶ä¸Žéžé™åˆ¶ç‰¹å¾.

Transpiration is a significant part of water cycle in forest ecosystems, influenced by meteorological factors and potentially constrained by soil moisture. We used Granier-type thermal dissipation probes to monitor xylem sap flow dynamics of three tree species (Quercus liaotungensis, Platycladus orientalis, and Robinia pseudoacacia) in a semi-arid loess hilly region, and to continuously monitor the key meteorological factors and soil water content (SWC). We established the SWC thresholds delineating soil moisture-limited and -unlimited sap flow responses to transpiration drivers. The results showed that mean sap flux density (Js) of Q. liaotungensis and R. pseudoacacia was significantly higher during period with higher soil moisture compared to lower soil moisture, while the difference in Js for P. orientalis between the two periods was not significant. We used an exponential saturation function to fit the relationship between the Js of each tree species and the integrated transpiration variable (VT) which reflected solar radiation and vapor pressure deficit. The difference in the fitting curve parameters indicated that there were distinct response patterns between Js and VT under different soil moisture conditions. There was a threshold in soil moisture limitation on sap flow for each species, which was identified as 0.129 m3·m-3 for Q. liaotungensis, 0.116 m3·m-3 for P. orientalis, and 0.108 m3·m-3 for R. pseudoacacia. Below the thresholds, Js was limited by soil moisture. Above these points, the normalized sensitivity index (NSI) for Q. liaotungensis and P. orientalis reached saturation, while that of R. pseudoacacia did not reach saturation but exhibited a significant reduction in moisture limitation. Among the three species, P. orientalis was the most capable of overcoming soil moisture constraints.

Nodule-in-nodule architecture of hepatocellular carcinomas: enhancement patterns in the hepatobiliary phase and pathological features.

PURPOSE: This study aimed to evaluate the enhancement patterns in the hepatobiliary phase (HBP) and pathological features of nodule-in-nodule-type hepatocellular carcinoma (NIN-HCC) patients. METHODS: In this single-institution retrospective study, 27 consecutive cirrhosis patients with 29 histologically confirmed NIN-HCCs who underwent preoperative examination via Gd-EOB-DTPA-enhanced MRI were enrolled from January 2016 to September 2023. Two blinded radiologists assessed the imaging features of both the inner and outer nodules in NIN-HCCs to reach a consensus on the Liver Imaging Reporting & Data System (LI-RADS) categories of the lesions. Based on the different enhancement patterns of the inner and outer nodules in the HBP, NIN-HCCs were classified into different groups and further divided into different types. Imaging features and LI-RADS categories were subsequently compared among the groups. Pathological findings for NIN-HCCs were also evaluated. RESULTS: Among 29 NIN-HCCs, all inner nodules showed hypervascularity, with a maximum diameter of 13.2 ± 5.5 mm; 51.7% (15/29) showed "wash-in with washout" enhancement; and 48.3% (14/29) showed "wash-in without washout" enhancement. All outer nodules showed hypovascularity, with a maximum diameter of 25.6 ± 7.3 mm, and 51.9% (14/29) showed a washout appearance on PVP. Among all the lesions, the maximum diameter was 27.5 ± 6.8 mm; 12 (41.4%) lesions were LR-4, and 17 (58.6%) lesions were LR-5. NIN-HCCs were classified into hypointense (62.1%, 18/29) and isointense (37.9%, 11/29) groups based on the signal intensity of the outer nodules in the HBP. In the hypointense group, 2 (6.9%) of the inner nodules were hypointense (type A), 11 (37.9%) were isointense (type B), and 5 (17.2%) were hyperintense (type C) compared to the background hypointense outer nodules. In the isointense group, 9 (31.0%) of the inner nodules were hypointense (type D), 2 (6.9%) were isointense (type E), and no (0%) was hyperintense (type F) compared to the background isointense outer nodules. There were no significant differences in the diameter, dynamic enhancement patterns of the inner or outer nodules, or LI-RADS scores of the lesions between the hypointense group and the isointense group (all P > 0.05). Histologically, the inner nodules of NIN-HCCs were mainly composed of moderately differentiated HCC (75.9% 22/29), whereas the outer nodules consisted of either well-differentiated HCC or high-grade dysplastic nodules (HGDNs). CONCLUSIONS: NIN-HCCs exhibit specific MRI findings closely associated with their pathological features. The spectrum of HBP enhancement patterns provides valuable insights into the underlying cell biological mechanisms of these lesions. NIN-HCC subtypes may be used as a morphologic marker in the early stage of multistep hepatocarcinogenesis.

Prediction of university fund revenue and expenditure based on fuzzy time series with a periodic factor.

Financial management and decision-making of universities play an essential role in their development. Predicting fund revenue and expenditure of universities can provide a necessary basis for funds risk prevention. For the lack of solid data reference for financial management and funds risk prevention in colleges and universities, this paper presents a prediction model of University fund revenue and expenditure based on fuzzy time series with a periodic factor. Combined with the fuzzy time series, this prediction method introduces the periodic factor of university funds. The periodic factor is used to adjust the proportion of the predicted value of the fuzzy time series and the periodic observation value. A fund revenue prediction model and a fund expenditure prediction model are constructed, and an experiment is carried out with the actual financial data of a university in China. The experimental result shows the effectiveness of the proposed model, which can provide solid references for financial management and funds risk prevention in universities.

A scientometrics and visualization analysis of oxidative stress modulator Nrf2 in cancer profiles its characteristics and reveals its association with immune response.

Background: Nrf2, an essential and fascinating transcription factor, enjoys a dual property in the occurrence and development of inflammation and cancer. For over two decades, numerous studies regarding Nrf2 in cancer have been reported, whereas there is still a lack of a scientometrics and visualization analysis of Nrf2 in cancer. Hence, a scientometric study regarding the oxidative stress modulator Nrf2 was implemented. Methods: After the quality screening, we defined 7168 relevant studies from 2000 to 2021. CiteSpace, VOSviewer, R software, and GraphPad Prism were used for the following scientometric study and visualization analysis, including field profiles, research hotspots, and future predictions. Results: The total number of publications and citations are 1058 and 54,690, respectively. After polynomial fitting curve analysis, two prediction functions of the annual publication number (y = 3.3909x2 - 13585x + 1 E+07) and citation number (185.45x2 - 743669x + 7 E+08) were generated. After scientometric analysis, we found that Biochemistry Molecular Biology correlates with Nrf2 in cancer highly, and Free Radical Biology and Medicine is a good choice for submitting Nrf2-related manuscripts. The current research hotspots of Nrf2 in cancer mainly focus on cancer therapy and its cellular and molecular mechanisms. "antioxidant response element (87.5)", "gene expression (43.98)", "antioxidant responsive element (21.14)", "chemoprevention (20.05)", "carcinogenesis (19.2)", "cancer chemoprevention (18.45)", "free radical (17.15)", "response element (14.17)", and "chemopreventive agent (14.04)" are important for cancer therapy study. In addition, "glutathione-S-transferase (47)", "keap1 (15.39)", and "heme oxygenase 1 gene (24.35)" are important for inflammation and cell fate study. More interestingly, by performing an "InfoMap" algorithm, the thematic map showed that the "immune response" is essential to oxidative stress modulator Nrf2 but not well developed, indicating it deserves further exploration. Conclusion: This study revealed field profiles, research hotspots, and future directions of oxidative stress modulator Nrf2 in inflammation and cancer research, and our findings will offer a vigorous roadmap for further studies in this field.

The mitochondrial protein TIMM44 is required for angiogenesis in vitro and in vivo.

The mitochondrial integrity and function in endothelial cells are essential for angiogenesis. TIMM44 (translocase of inner mitochondrial membrane 44) is essential for integrity and function of mitochondria. Here we explored the potential function and the possible mechanisms of TIMM44 in angiogenesis. In HUVECs, human retinal microvascular endothelial cells and hCMEC/D3 brain endothelial cells, silence of TIMM44 by targeted shRNA largely inhibited cell proliferation, migration and in vitro capillary tube formation. TIMM44 silencing disrupted mitochondrial functions in endothelial cells, causing mitochondrial protein input arrest, ATP reduction, ROS production, and mitochondrial depolarization, and leading to apoptosis activation. TIMM44 knockout, by Cas9-sgRNA strategy, also disrupted mitochondrial functions and inhibited endothelial cell proliferation, migration and in vitro capillary tube formation. Moreover, treatment with MB-10 ("MitoBloCK-10"), a TIMM44 blocker, similarly induced mitochondrial dysfunction and suppressed angiogenic activity in endothelial cells. Contrarily, ectopic overexpression of TIMM44 increased ATP contents and augmented endothelial cell proliferation, migration and in vitro capillary tube formation. In adult mouse retinas, endothelial knockdown of TIMM44, by intravitreous injection of endothelial specific TIMM44 shRNA adenovirus, inhibited retinal angiogenesis, causing vascular leakage, acellular capillary growth, and retinal ganglion cells degeneration. Significant oxidative stress was detected in TIMM44-silenced retinal tissues. Moreover, intravitreous injection of MB-10 similarly induced oxidative injury and inhibited retinal angiogenesis in vivo. Together, the mitochondrial protein TIMM44 is important for angiogenesis in vitro and in vivo, representing as a novel and promising therapeutic target of diseases with abnormal angiogenesis.

Cholesterol paradox in the community-living old adults: is higher better?

OBJECTIVE: To evaluate the associations of lipid indicators and mortality in Beijing Elderly Comprehensive Health Cohort Study. METHODS: A prospective cohort was conducted based on Beijing Elderly Comprehensive Health Cohort Study with 4499 community older adults. After the baseline survey, the last follow-up was March 31, 2021 with an average 8.13 years of follow-up. Cox proportional hazard model was used to estimate the hazard ratios (HR) with 95% CI for cardiovascular disease (CVD) death and all-cause death in associations with baseline lipid indicators. RESULTS: A total of 4499 participants were recruited, and the mean levels of uric acid, body mass index, systolic blood pressure, diastolic blood pressure, fasting plasma glucose, total cholesterol (TC), triglyceride, and low-density lipoprotein cholesterol (LDL-C) showed an upward trend with the increasing remnant cholesterol (RC) quarters (Ptrend < 0.05), while the downward trend was found in high-density lipoprotein cholesterol (HDL-C). During the total 36,596 person-years follow-up, the CVD mortality and all-cause mortality during an average 8.13 years of follow-up was 3.87% (95% CI: 3.30%-4.43%) and 14.83% (95% CI: 13.79%-15.86%) with 174 CVD death participants and 667 all-cause death participants. After adjusting for confounders, the higher level of TC (HR = 0.854, 95% CI: 0.730-0.997), LDL-C (HR = 0.817, 95% CI: 0.680-0.982) and HDL-C (HR = 0.443, 95% CI: 0.271-0.724) were associated with lower risk of CVD death, and the higher level of HDL-C (HR = 0.637, 95% CI: 0.501-0.810) were associated with lower risk of all-cause death. The higher level of RC (HR = 1.276, 95% CI: 1.010-1.613) increase the risk of CVD death. Compared with the normal lipid group, TC ≥ 6.20 mmol/L group and LDL-C ≥ 4.10 mmol/L group were no longer associated with lower risk of CVD death, while RC ≥ 0.80 mmol/L group was still associated with higher risk of CVD death. In normal lipid group, the higher levels of TC, LDL-C and HDL-C were related with lower CVD death. CONCLUSIONS: In community older adults, higher levels of TC and HDL-C were associated with lower CVD mortality in normal lipid reference range. Higher RC was associated with higher CVD mortality, which may be a better lipid indicator for estimating the CVD death risk in older adults.

Highly selective adsorption of methanol in carbon nanotubes immersed in methanol-water solution.

The systems of open-ended carbon nanotubes (CNTs) immersed in methanol-water solution are studied by molecular dynamics simulations. For the (6,6) CNT, nearly pure methanol is found to preferentially occupy interior space of the CNT. Even when the mass fraction (MF) of methanol in bulk solution is as low as 1%, the methanol MF within the CNT is still more than 90%. For CNTs with larger diameters, the methanol concentrations within CNTs are also much higher than those outside CNTs. The methanol selectivity decreases with increasing CNT diameter, but not monotonically. From microscopic structural analyses, we find that the primary reason for the high selectivity of methanol by CNTs lies on high preference of methanol in the first solvation shell near the inner wall of CNT, which stems from a synergy effect of the van der Waals interaction between CNT and the methyl groups of methanol, together with the hydrogen bonding interaction among the liquid molecules. This synergy effect may be of general significance and extended to other systems, such as ethanol aqueous solution and methanol/ethanol mixture. The selective adsorption of methanol over water in CNTs may find applications in separation of water and methanol, detection of methanol, and preservation of methanol purity in fuel cells.