ATF5 Connects the Pericentriolar Materials to the Proximal End of the Mother Centriole.

Although it is known that the centrioles play instructive roles in pericentriolar material (PCM) assembly and that the PCM is essential for proper centriole formation, the mechanism that governs centriole-PCM interaction is poorly understood. Here, we show that ATF5 forms a characteristic 9-fold symmetrical ring structure in the inner layer of the PCM outfitting the proximal end of the mother centriole. ATF5 controls the centriole-PCM interaction in a cell-cycle- and centriole-age-dependent manner. Interaction of ATF5 with polyglutamylated tubulin (PGT) on the mother centriole and with PCNT in the PCM renders ATF5 as a required molecule in mother centriole-directed PCM accumulation and in PCM-dependent centriole formation. ATF5 depletion blocks PCM accumulation at the centrosome and causes fragmentation of centrioles, leading to the formation of multi-polar mitotic spindles and genomic instability. These data show that ATF5 is an essential structural protein that is required for the interaction between the mother centriole and the PCM.

Habitat quality dynamics in China's first group of national parks in recent four decades: Evidence from land use and land cover changes.

As the most biodiversity-rich part of the protected areas system, habitats within the pilot national parks have long been threatened by drastic human-induced land use and land cover changes. The growing concern about habitat loss has spurred China's national park project to shift from pilot to construction phase with the official establishment of China's first group of national parks (CFGNPs) in October 2021. But far too little attention has been paid to the synergistic work concerning the habitat quality (HQ) dynamics of all five national parks. Here, the InVEST model, combined with a satellite-derived land use and land cover product and a hot spot analysis (HSA) method, was used to investigate the HQ dynamics at the park- and pixel-scale within the CFGNPs. Our results demonstrate that the past ecological conservation practices within national parks have been unpromising, especially in Giant Panda National Park, Northeast China Tiger and Leopard National Park (NCTL), and Wuyi Mountain National Park (WYM), where HQ as a whole showed a significant decline. Furthermore, more than half of Hainan Tropical Rainforest National Park (87.2%), WYM (77.4%), and NCTL (52.9%) showed significant HQ degradation from 1980 to 2019. Besides, increasing trends in the area shares of HQ degraded pixels were observed in all five national parks from 1980-1999 to 2000-2019. The HSA implied that the hot spots of high HQ degradation rates tend to occur in areas closer to urban settlements or on the edge of national parks, where human activities are intensive. Despite these disappointing findings, we highlighted from the observed local successes and the HQ plateau that the construction of CFGNPs is expected to reverse the deteriorating HQ trends. Thus, we concluded our paper by proposing an HSA-based regulatory zoning scheme that includes five subzones to guide the future construction of China's national park system.

Contribution of Digital Subtraction Angiogram in Diagnosis and Anatomic Recognition of Traumatic Pulsatile Mass.

Traumatic pulsating masses are difficult to make a definitive diagnosis due to anatomic variation of malformed vessels and rarely clinical incidence. It is essentially to recognizing the anatomy of such vessels, otherwise it may lead to an improperly treatment or serious complication. Digital subtraction angiogram (DSA) has a distinct advantage in both diagnosis and treatment of this subject. Here the authors report a case of venous malformation in the supraclavicular fossa with an underlying arteriovenous fistula following nonoperative management of a clavicle fracture in an adult, and discuss how to rule out potential differential diagnoses and get minimally invasive treatment with DSA.

SUMO2/3 modification of activating transcription factor 5 (ATF5) controls its dynamic translocation at the centrosome.

Activating transcription factor 5 (ATF5) is a member of the ATF/cAMP response element-binding protein family of transcription factors. ATF5 regulates stress responses and cell survival, proliferation, and differentiation and also plays a role in viral infections, cancer, diabetes, schizophrenia, and the olfactory system. Moreover, it was found to also have a critical cell cycle-dependent structural function at the centrosome. However, the mechanism that controls the localization of ATF5 at the centrosome is unclear. Here we report that ATF5 is small ubiquitin-like modifier (SUMO) 2/3-modified at a conserved SUMO-targeting consensus site in various types of mammalian cells. We found that SUMOylation of ATF5 is elevated in the G1 phase of the cell cycle and diminished in the G2/M phase. ATF5 SUMOylation disrupted the interaction of ATF5 with several centrosomal proteins and dislodged ATF5 from the centrosome at the end of the M phase. Of note, blockade of ATF5 SUMOylation deregulated the centrosome cycle, impeded ATF5 translocation from the centrosome, and caused genomic instability and G2/M arrest in HeLa cells. Our results indicate that ATF5 SUMOylation is an essential mechanism that regulates ATF5 localization and function at the centrosome.

Trim21 Regulates the Postnatal Development and Thermogenesis of Brown Adipose Tissue.

Brown adipose tissue undergoes rapid postnatal development to mature and plays a crucial role in thermoregulation and energy expenditure, which protects against cold and obesity. Herein, it is shown that the expression of Trim21 mRNA level of interscapular brown adipose tissue elevates after birth, and peaks at P14 (postnatal day 14). Trim21 depletion severely impairs the maturation of interscapular brown adipose tissue, decreases the expression of a series of thermogenic genes, and reduces energy expenditure. Consistently, the loss of Trim21 also leads to a suppression of white adipose tissue "browning", in response to cold exposure and a ß-adrenergic agonist, CL316,243. In addition, Trim21-/- mice are more prone to high-fat diet-induced obesity compared with the control littermates. Taken together, the study for the first time reveals a critical role of Trim21 in regulating iBAT postnatal development and thermogenesis.

Targeting YAP1-regulated Glycolysis in Fibroblast-Like Synoviocytes Impairs Macrophage Infiltration to Ameliorate Diabetic Osteoarthritis Progression.

The interplay between immune cells/macrophages and fibroblast-like synoviocytes (FLSs) plays a pivotal role in initiating synovitis; however, their involvement in metabolic disorders, including diabetic osteoarthritis (DOA), is largely unknown. In this study, single-cell RNA sequencing (scRNA-seq) is employed to investigate the synovial cell composition of DOA. A significant enrichment of activated macrophages within eight distinct synovial cell clusters is found in DOA synovium. Moreover, it is demonstrated that increased glycolysis in FLSs is a key driver for DOA patients' synovial macrophage infiltration and polarization. In addition, the yes-associated protein 1 (YAP1)/thioredoxin-interacting protein (TXNIP) signaling axis is demonstrated to play a crucial role in regulating glucose transporter 1 (GLUT1)-dependent glycolysis in FLSs, thereby controlling the expression of a series of adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) which may subsequently fine-tune the infiltration of M1-polarized synovial macrophages in DOA patients and db/db diabetic OA mice. For treatment, M1 macrophage membrane-camouflaged Verteporfin (Vt)-loaded PLGA nanoparticles (MVPs) are developed to ameliorate DOA progression by regulating the YAP1/TXNIP signaling axis, thus suppressing the synovial glycolysis and the infiltration of M1-polarized macrophages. The results provide several novel insights into the pathogenesis of DOA and offer a promising treatment approach for DOA.

Apoptotic body-inspired nanotherapeutics efficiently attenuate osteoarthritis by targeting BRD4-regulated synovial macrophage polarization.

Bromodomain-containing protein 4 (BRD4) is the most well-studied BET protein that is important for the innate immune response. We recently revealed that targeting BRD4 triggers apoptosis in tumor-associated macrophages, but its role in synovial macrophages and joint inflammation is largely unknown. Herein, we demonstrated that BRD4 was highly expressed in the iNOS-positive M1 macrophages in the human and mouse osteoarthritis (OA) synovium, and conditional knockout of BRD4 in the myeloid lineage using Lyz2-cre; BRD4flox/flox mice significantly abolished anterior cruciate ligament transection (ACLT)-induced M1 macrophage accumulation and synovial inflammation. Accordingly, we successfully constructed apoptotic body-inspired phosphatidylserine-containing nanoliposomes (PSLs) loaded with the BRD4 inhibitor JQ1 to regulate inflammatory macrophages. JQ1-loaded PSLs (JQ1@PSLs) exhibited a higher cellular uptake by macrophages than fibroblast-like synoviocytes (FLSs) in vitro and in vivo, as well as the reduction in proinflammatory M1 macrophage polarization. Intra-articular injections of JQ1@PSLs showed prolonged retention within the joint, and remarkably reduced synovial inflammation and joint pain via suppressing M1 polarization accompanied by reduced TRPA1 expression by targeted inhibition of BRD4 in the macrophages, thus attenuating cartilage degradation during OA development. The results show that BRD4-inhibiting JQ1@PSLs can targeted-modulate macrophage polarization, which opens a new avenue for efficient OA therapy via a "Trojan horse".

High-Efficiency Antibacterial Hemostatic AgNP@Zeolite/Chitin/Bamboo Composite Sponge for Wound Healing without Heat Injury.

Chitin is a popular hemostatic material, but there are still many deficiencies in its ability to effectively stop bleeding, prevent infection, and fit wounds. Herein, AgNP@zeolite/chitin/bamboo (AgZ-CB) composite sponges with shape recovery are prepared to minimize blood loss, kill bacteria, and promote wound healing. Notably, the bamboo powder is used for the first time to remarkably enhance the softness of the composite sponge (volumetric expansion ratio >5). The fabricated AgZ-CB sponge exhibits an excellent killing effect (≈100% bactericidal rate) against both Escherichia coli and Staphylococcus aureus and activates internal and external coagulation pathways to accelerate hemostasis without causing thermal damage (≈5 °C temperature difference). Moreover, the AgZ-CB sponge shows less blood loss (26 mg) and a shorter time to hemostasis (42 s) than the commercial polyvinyl formal sponge (84 mg and 76 s) in the full-thickness liver injury model. The in vivo wound healing and biodegradation experiment indicate that AgZ-CB with excellent biocompatibility can close wounds efficiently. Overall, the AgZ-CB sponge has great potential in combating a series of obstacles in wound healing.

Effect of acupuncture at neck-Jiaji (EX-B 2) and tuina on the cognitive function in the patients with subjective cognitive decline. / é’ˆåˆºé¢ˆå¤¹è„Šç©´è”åˆæŽ¨æ‹¿å¯¹ä¸»è§‚è®¤çŸ¥ä¸‹é™æ‚£è€ è®¤çŸ¥åŠŸèƒ½çš„å½±å“.

OBJECTIVES: To observe the effects on cognitive function, sleep quality and hemodynamics in the patients with subjective cognitive decline (SCD) after treated with acupuncture at neck-Jiaji (EX-B 2) and tuina on the base of healthy lifestyle education and meta-memory training. METHODS: Sixty SCD patients were randomly divided into an observation group (30 cases, 1 case dropped out) and a control group (30 cases, 3 cases dropped out). In the control group, the healthy lifestyle education and meta-memory training was performed, twice daily, 15 min each time; the 5-day intervention was delivered a week, lasting consecutively 4 weeks. On the base of the intervention as the control group, in the observation group, acupuncture at neck-Jiaji (EX-B 2) and tuina was conducted. First, one-finger pushing and plucking method of tuina was exerted on the neck region along the running courses of the bladder meridian of foot-taiyang and the governor vessel, for 10 min to 15 min; afterwards, acupuncture was delivered at bilateral neck-Jiaji (EX-B 2), from C1 to C7; and the needles were retained for 30 min. This intervention was given once daily, 5 times a week, for consecutive 4 weeks. Before and after treatment, the score of the mini-mental state examination (MMSE), the score of full scale memory quotient (FSMQ) were assessed by Wechsler memory scale-fourth edition (WMS-Ⅳ) and the score of the Pittsburgh sleep quality index (PSQI) was compared between the two groups. Using transcranial Doppler ultrasound, the hemodynamic indexes (the mean velocity [Vm] and pulsatility index [PI] of the left vertebral artery [LVA], the right vertebral artery [RVA] and the basilar artery [BA]) were determined in the two groups. RESULTS: After treatment, the scores of MMSE and FSMQ increased compared with those before treatment in the two groups (P<0.05, P<0.001), PSQI score was lower (P<0.05) and Vm of BA was higher (P<0.001) in the observation group when compared with those before treatment. The scores of MMSE and FSMQ, as well as Vm of BA were higher (P<0.05, P<0.001), and PSQI score was decreased (P<0.05) in the observation group when compared with the control group. CONCLUSIONS: The combined therapy of acupuncture at neck-Jiaji (EX-B 2) and tuina is more advantageous to improving cognitive function, relieving chronic emotional stress and ameliorating sleeping quality in the patients with subjective cognitive decline, which may be achieved by improving the blood supply of the basilar artery.

Temperature extremes of 2022 reduced carbon uptake by forests in Europe.

The year 2022 saw record breaking temperatures in Europe during both summer and fall. Similar to the recent 2018 drought, close to 30% (3.0 million km2) of the European continent was under severe summer drought. In 2022, the drought was located in central and southeastern Europe, contrasting the Northern-centered 2018 drought. We show, using multiple sets of observations, a reduction of net biospheric carbon uptake in summer (56-62 TgC) over the drought area. Specific sites in France even showed a widespread summertime carbon release by forests, additional to wildfires. Partial compensation (32%) for the decreased carbon uptake due to drought was offered by a warm autumn with prolonged biospheric carbon uptake. The severity of this second drought event in 5 years suggests drought-induced reduced carbon uptake to no longer be exceptional, and important to factor into Europe's developing plans for net-zero greenhouse gas emissions that rely on carbon uptake by forests.

HSP70 protein promotes survival of C6 and U87 glioma cells by inhibition of ATF5 degradation.

Although both the heat shock protein 70 (HSP70) and the activating transcription factor 5 (ATF5) have been shown to promote cell survival of transformed cells but not survival of non-transformed cells, the relationship of the two molecules is unknown. Here we show that HSP70 and ATF5 are concomitantly up-regulated upon transient but down-regulated over prolonged cellular stress and apoptotic stimulation in the rat C6 glioma and human U87 glioma cells. HSP70 interacts strongly with the N-terminal activation domain of ATF5, which is expected to be rigid and uniquely structured under physiological conditions because of extraordinary high concentration (over 25%) of proline residues. Binding of HSP70 to ATF5 is an ATP-driven process and requires functional ATPase on the nucleotide binding domain of the HSP70 molecule. Overexpression of HSP70 dramatically stabilizes the ATF5 protein, which is otherwise subject to rapid degradation, facilitated by both proteasome-dependent and caspase-dependent processes, whereas HSP70 depletion leads to acceleration of ATF5 degradation and transcription repression of Bcl-2 and Egr-1, which are downstream targets of ATF5 in C6 and U87 glioma cells. Our data reveal an essential role for HSP70 in maintaining high levels of ATF5 expression in glioma cells and support the conclusion that ATF5 is an important substrate protein of HSP70 that mediates HSP70-promoted cell survival in glioma cells.

Distribution of ecological restoration projects associated with land use and land cover change in China and their ecological impacts.

China is prone to broad land degradation and thus has been implementing ecological restoration projects (ERPs) since the reform and opening up. The extent of ERPs, as well as the varied planting efforts including tree gain projects (TGPs), grass gain projects (GGPs), and shrub gain projects (SGPs), have remained largely unknown. In addition, the mixed success of ERPs on preventing soil erosion and improving biodiversity is not well known. Based on a land use and land cover (LULC) product and a trajectory-based change detection approach, we successfully generated the first national map of ERPs associated with land use and land cover change (LUCC) and its three associated subcategories. Then, we applied the Integrated Valuation of Ecosystem Services and Tradeoffs (InVEST) model to evaluate the dynamics of sediment retention and habitat quality. In addition, we explored the heterogeneous patterns for the ecological impacts of ERPs. Our results suggested that during the past 40 years, a total ERP area of 9.54 × 106 hm2 was observed nationwide, mainly in the northwestern provinces of China. Of the three ERP subcategories, TGPs accounted for the largest area (48.55%), followed by GGPs (47.50%) and SGPs (3.96%). The national average sediment retention experienced a significant increase, whereas the national average habitat quality experienced a significant decline. ERP-driven increases in habitat quality were offset partly by the LUCCs induced by economic development policies in some regions, especially in northeast China. The simultaneous effect of construction land expansion and ERP implementation on sediment retention made the synchronization between ERP implementation and sediment retention improvement insignificant. We also suggested the optimal direction for ERP implementation.

A global map of planting years of plantations.

Plantation is an important land use type that differs from natural forests and affects the economy and the environment. Tree age is one of the key factors used to quantify the impact of plantations. However, there is a lack of datasets explicitly documenting the planting years of global plantations. Here we used time-series Landsat archive from 1982 to 2020 and the LandTrendr algorithm to generate global maps of planting years based on the global plantation extent products in Google Earth Engine (GEE) platform. The datasets developed in this study are in a GeoTIFF format with 30-meter spatial resolution by recording gridded specie types and planting years of global plantations. The derived dataset could be used for yield prediction of tree crops and social and ecological cost-benefit analysis of plantations.

Detecting Amyloid-ß Accumulation via Immunofluorescent Staining in a Mouse Model of Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative disease that contributes to 60-70% dementia around the world. One of the hallmarks of AD undoubtedly lies on accumulation of amyloid-ß (Aß) in the brain. Aß is produced from the proteolytic cleavage of the beta-amyloid precursor protein (APP) by ß-secretase and γ-secretase. In pathological circumstances, the increased ß-cleavage of APP leads to overproduction of Aß, which aggregates into Aß plaques. Since Aß plaques are a characteristic of AD pathology, detecting the amount of Aß is very important in AD research. In this protocol, we introduce the immunofluorescent staining method to visualize Aß deposition. The mouse model used in our experiments is 5×FAD, which carries five mutations found in human familial AD. The neuropathological and behavioral deficits of 5xFAD mice are well-documented, which makes it a good animal model to study Aß pathology. We will introduce the procedure including transcardial perfusion, cryosectioning, immunofluorescent staining and quantification to detect Aß accumulation in 5×FAD mice. With this protocol, researchers can investigate Aß pathology in an AD mouse model.

Cropland heterogeneity changes on the Northeast China Plain in the last three decades (1980s-2010s).

The Northeast China Plain is one of the major grain-producing areas of China because of its fertile black soil and large fields adapted for agricultural machinery. It has experienced some land-use changes, such as urbanization, deforestation, and wetland reclamation in recent decades. A comprehensive understanding of these changes in terms of the total cropping land and its heterogeneity during this period is important for policymakers. In this study, we used a series of cropland products at the 30-m resolution for the period 1980-2015. The heterogeneity for dominant cropland decreased slowly over the three decades, especially for the large pieces of cropland, showing a general trend of increased cropland homogeneity. The spatial patterns of the averaged heterogeneity index were nearly the same, varying from 0.5 to 0.6, and the most heterogeneous areas were mainly located in some separate counties. Cropland expansion occurred across most of Northeast China, while cropland shrinking occurred only in the northern and eastern sections of Northeast China and around the capital cities, in the flat areas. Also, changes in land use away from cropland mainly occurred in areas with low elevation (50-200 m) and a gentle slope (less than 1 degree). The predominant changes in cropland were gross gain and homogeneity, occurring across most of the area except capital cities and boundary areas. Possible reasons for the total cropland heterogeneity changes were urbanization, restoration of cropland to forest, and some government land-use policies. Moreover, this study evaluates the effectiveness of cropland policies influencing in Northeast China.

The first all-season sample set for mapping global land cover with Landsat-8 data.

We report the world's first all-season training and validation sample sets for global land cover classification with Landsat-8 data. Prior to this, such samples were only available at a single date primarily from the growing season. It is unknown how much limitation such a single-date sample has to mapping global land cover in other seasons of the year. To answer this question, we selected available Landsat-8 images from four seasons and collected training and validation samples from them. We compared the performances of training samples in different seasons using Random Forest algorithm. We found that the use of training samples from any individual season would result in the best overall classification accuracy when validated by samples in the same season. The global overall accuracy from combined best seasonal results was 67.2% when classifying the 11 Level-1 classes in the Finer Resolution Observation and Monitoring of Global Land Cover (FROM-GLC) classification system. The use of training samples from all seasons (named all-season training sample set hereafter) produced an overall accuracy of 67.0%. We also tested classification within 10° latitude 60° longitude zones using all-season training subsample within each zone and obtained an overall accuracy of 70.2%. This indicates that properly grouped subsamples in space can help improve classification accuracies. All the results in this study seem to suggest that it is possible to use an all-season training sample set to reach global optimality with universal applicability in classifying images acquired at any time of a year for global land cover mapping.

The complete mitochondrial genome of Buccinum pemphigum (Neogastropoda: Buccinidae).

In this study, the complete mitogenome of Buccinum pemphigum has been determined. The complete mitochondrial genome is 15 265 bp in length, including 13 protein-coding genes, two rRNA genes and 22 tRNA genes. The total base composition is 30.1% A, 15.8% G, 15.1% C and 39.0%T, with a high AT content of 69.1%. Tree constructed using maximum-likelihood (ML) phylogenetic method, demonstrated that B. pemphigum has a close relationship to Volutharpa perryi clustered in Buccinoidea. First, this complete mitogenome of Buccinum will facilitate the development of new DNA markers for species identification.

Complete mitochondrial genome of Volutharpa perryi (Neogastropoda: Buccinidae).

In this study, the complete mitochondrial genome of Volutharpa perryi has been determined for the first time. The mitogenome is of 15 255 bp in length, including 13 protein-coding genes, two ribosomal RNA genes and 22 transfer RNA genes. The overall base composition is 29.6%, 38.6%, 15.6% and 16.2% for A, T, C and G, respectively. The 13 PCGs of V. perryi and other 12 mollusk species were used for phylogenetic analysis by maximum-likelihood method, and the phylogenetic tree demonstrated the close relationship of V. perryi to species of Buccinoidea. The results are expected to provide useful molecular data for species identification and further phylogenetic studies of genus Volutharpa.