Dysregulated prefrontal control over amygdala is engaged in the pathogenesis of psychiatric diseases including depression and anxiety disorders. Here we show that, in a rodent anxiety model induced ...by chronic restraint stress (CRS), the dysregulation occurs in basolateral amygdala projection neurons receiving mono-directional inputs from dorsomedial prefrontal cortex (dmPFC→BLA PNs) rather than those reciprocally connected with dmPFC (dmPFC↔BLA PNs). Specifically, CRS shifts the dmPFC-driven excitatory-inhibitory balance towards excitation in the former, but not latter population. Such specificity is preferential to connections made by dmPFC, caused by enhanced presynaptic glutamate release, and highly correlated with the increased anxiety-like behavior in stressed mice. Importantly, low-frequency optogenetic stimulation of dmPFC afferents in BLA normalizes the enhanced prefrontal glutamate release onto dmPFC→BLA PNs and lastingly attenuates CRS-induced increase of anxiety-like behavior. Our findings thus reveal a target cell-based dysregulation of mPFC-to-amygdala transmission for stress-induced anxiety.
Peroxisomes account for ~35% of total H2O2 generation in mammalian tissues. Peroxisomal ACOX1 (acyl‐CoA oxidase 1) is the first and rate‐limiting enzyme in fatty acid β‐oxidation and a major producer ...of H2O2. ACOX1 dysfunction is linked to peroxisomal disorders and hepatocarcinogenesis. Here, we show that the deacetylase sirtuin 5 (SIRT5) is present in peroxisomes and that ACOX1 is a physiological substrate of SIRT5. Mechanistically, SIRT5‐mediated desuccinylation inhibits ACOX1 activity by suppressing its active dimer formation in both cultured cells and mouse livers. Deletion of SIRT5 increases H2O2 production and oxidative DNA damage, which can be alleviated by ACOX1 knockdown. We show that SIRT5 downregulation is associated with increased succinylation and activity of ACOX1 and oxidative DNA damage response in hepatocellular carcinoma (HCC). Our study reveals a novel role of SIRT5 in inhibiting peroxisome‐induced oxidative stress, in liver protection, and in suppressing HCC development.
Synopsis
This study reveals a role for SIRT5 in regulating peroxisomal H2O2 and ROS homeostasis and indicates its potential function in liver protection and hepatocellular carcinoma suppression.
SIRT5 is localized in peroxisomes where it controls H2O2 metabolism.
SIRT5‐mediated desuccinylation inhibits ACOX1 activity by suppressing its active dimer formation.
SIRT5 downregulation increases ACOX1 activity and oxidative DNA damage response in HCC.
This study reveals a role for SIRT5 in regulating peroxisomal H2O2 and ROS homeostasis and indicates its potential function in liver protection and hepatocellular carcinoma suppression.
Various surgical techniques and conservative therapies are useful tools for treating proximal humerus fractures (PHFs), but it is important to understand how to properly utilize them. Therefore, we ...performed a systematic review and network meta-analysis to compare and rank the efficacy and safety of medical treatments for PHF.
PubMed, Embase, the Cochrane Library, and the ClinicalTrials.gov databases were systematically searched for eligible randomized controlled trials (RCTs) from inception until June 2022. Conservative therapy-controlled or head-to-head RCTs of open reduction internal fixation (ORIF), intramedullary nailing (IMN), hemiarthroplasty (HA), and reverse total shoulder arthroplasty (RTSA) used for the treatment of adult patients with PHF were included. The surface under the cumulative ranking (SUCRA) probabilities were applied to compare and rank the effects of medical treatments for PHF.
Eighteen RCTs involving 1,182 patients with PHF were selected for the final analysis. Mostly baseline characteristics among groups were well balanced, and the imbalanced factors only included age, injury type, medial comminution, blood loss, and cognitive function in single trial. The SUCRA probabilities found that RTSA provided the best effect on the Constant-Murley score (SUCRA: 100.0%), and the disabilities of the arm, shoulder and hand (DASH) score (SUCRA: 99.0%). Moreover, HA (SUCRA: 85.5%) and RTSA (SUCRA: 68.0%) had a relatively better effect on health-related quality of life than the other treatment modalities. Furthermore, conservative therapy (SUCRA: 84.3%) and RTSA (SUCRA: 80.7%) were associated with a lower risk of secondary surgery. Finally, the best effects on the risk of complications are varied, including infection was observed with conservative therapy (SUCRA: 94.2%); avascular necrosis was observed in HA (SUCRA: 78.1%), nonunion was observed in RTSA (SUCRA: 69.6%), and osteoarthritis was observed in HA (SUCRA: 93.9%).
This study found that RTSA was associated with better functional outcomes, while the comparative outcomes of secondary surgery and complications varied. Optimal treatment for PHF should consider patient-specific factors.
Herein, a series of imidazo4,5-
1,10 phenanthroline derivatives RPIP (PIP = imidazo 4,5-
1,10 phenanthroline, R = NO₂,
; CF₃,
; Cl,
; OH,
) have been synthesized in yields of 82.3-94.7% at 100 °C ...under the irradiation of microwave. MTT assay has been utilized to evaluate the inhibitory activity (IC
) of these compounds against the growth of various tumor cells, and the results revealed that these compounds, especially
, exhibited excellent inhibitory activity against the growth of A549 cells with IC
of 15.03 μM. Moreover, it's also confirmed that
can penetrate into the membrane of tumor cells and distribute in mitochondria when observed under microscopy, resulting apoptosis of tumor cells. The further studies showed that
can bind to
G-quadruplex DNA, which demonstrated by the increase of melting point of
G4 DNA in the presence of
, as well as electronic titration and emission spectra. In a word, this kind of compound may develop as a potential apoptosis inducer in cancer chemotherapy via binding and stabilizing to the
G-quadruplex DNA.
Pathological TDP‐43 aggregation is characteristic of several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD‐TDP); however, how ...TDP‐43 aggregation and function are regulated remain poorly understood. Here, we show that O‐GlcNAc transferase OGT‐mediated O‐GlcNAcylation of TDP‐43 suppresses ALS‐associated proteinopathies and promotes TDP‐43's splicing function. Biochemical and cell‐based assays indicate that OGT's catalytic activity suppresses TDP‐43 aggregation and hyperphosphorylation, whereas abolishment of TDP‐43 O‐GlcNAcylation impairs its RNA splicing activity. We further show that TDP‐43 mutations in the O‐GlcNAcylation sites improve locomotion defects of larvae and adult flies and extend adult life spans, following TDP‐43 overexpression in Drosophila motor neurons. We finally demonstrate that O‐GlcNAcylation of TDP‐43 promotes proper splicing of many mRNAs, including STMN2, which is required for normal axonal outgrowth and regeneration. Our findings suggest that O‐GlcNAcylation might be a target for the treatment of TDP‐43‐linked pathogenesis.
SYNOPSIS
O‐GlcNAcylation of TDP‐43 suppresses TDP‐43 proteinophathies and promotes TDP‐43’s mRNA splicing activity, with potential implications for ALS/FTLD pathogenesis.
TDP‐43 can be O‐GlcNAcylated by the enzyme OGT in vitro and in vivo, and O‐GlcNAcylation of TDP‐43 suppresses protein aggregation and hyperphosphorylation.
TDP‐43 O‐GlcNAcylation affects the locomotion and longevity of Drosophila.
O‐GlcNAcylation of TDP‐43 prevents aberrant splicing of key neuron genes, such as STMN2, Dnajc5, and Sort1.
O‐GlcNAcylation of TDP‐43 suppresses TDP‐43 proteinophathies and promotes TDP‐43’s mRNA splicing activity, with potential implications for ALS/FTLD pathogenesis.
Display omitted
•Fast ion transport channels were built by CQDs interlayer of NF membrane.•CQDs/TFC membranes show high selectivity for amino acids and negative ions.•The membrane has great potential ...for valorization of biogas slurry.
In this article, novel nanofiltration (NF) membranes with highly selective surface and fast water and ion transport channels were fabricated for the valorization of biogas slurry. Unlike conventional thin film composite (TFC) membranes, the novel NF membranes compose hydrophilic carbon quantum dots (CQDs) as the interlayer. The carboxyl groups from CQDs react with the polyethyleneimine (PEI), leading to the lower cross-linking degree in the interfacial polymerization layer of NF membranes. Besides, the presence of the hydrophilic CQDs can create fast water and ion transport channels in the NF membranes. The water permeability of membranes is therefore enhanced significantly from 3.6 to 9.7 LMH·bar−1. The NF membranes were used to concentrate the amino acids from biogas slurry; it achieved rejection rates above 90% towards model amino acids such as lysine, glutamic acid and leucine, due to its highly positive electrical properties, while allowing most of the unwanted salt ions to permeate through. The excellent selectivity between amino acids and salt ions demonstrates the great potential application of the NF membranes in biogas slurry valorization.
Video and images acquired by a visual system are seriously degraded under hazy and foggy weather, which will affect the detection, tracking, and recognition of targets. Thus, restoring the true scene ...from such a foggy video or image is of significance. The main goal of this paper was to summarize current video and image defogging algorithms. We first presented a review of the detection and classification method of a foggy image. Then, we summarized existing image defogging algorithms, including image restoration algorithms, image contrast enhancement algorithms, and fusion-based defogging algorithms. We also presented current video defogging algorithms. We summarized objective image quality assessment methods that have been widely used for the comparison of different defogging algorithms, followed by an experimental comparison of various classical image defogging algorithms. Finally, we presented the problems of video and image defogging which need to be further studied. The code of all algorithms will be available at <;uri xlink:href="http://www.yongxu.org/lunwen.html" xlink:type="simple">http://www.yongxu.org/lunwen.html<;/uri>.
Previous assessments of the effectiveness of protected areas (PAs) focused primarily on changes in human pressure over time and did not consider the different human‐pressure baselines of PAs, thereby ...potentially over‐ or underestimating PA effectiveness. We developed a framework that considers both human‐pressure baseline and change in human pressure over time and assessed the effectiveness of 338 PAs in China from 2010 to 2020. The initial state of human pressure on PAs was taken as the baseline, and changes in human pressure index (HPI) were further analyzed under different baselines. We used the random forest models to identify the management measures that most improved effectiveness in resisting human pressure for the PAs with different baselines. Finally, the relationships between the changes in the HPI and the changes in natural ecosystems in PAs were analyzed with different baselines. Of PAs with low HPI baselines, medium HPI baselines, and high HPI baselines, 76.92% (n=150), 11.11% (n=12), and 22.86% (n=8) , respectively, showed positive effects in resisting human pressure. Overall, ignoring human‐pressure baselines somewhat underestimated the positive effects of PAs, especially for those with low initial human pressure. For PAs with different initial human pressures, different management measures should be taken to improve effectiveness and reduce threats to natural ecosystems. We believe our framework is useful for assessing the effectiveness of PAs globally, and we recommend it be included in the Convention on Biological Diversity Post‐2020 Strategy.
Resumen
Las evaluaciones previas de la efectividad de las áreas protegidas (AP) se han enfocado principalmente en los cambios de las presiones humanas con el tiempo y no han considerado las diferentes líneas base de las presiones humanas en las AP, por lo que potencialmente han sobrestimado o subestimado su efectividad. Desarrollamos un marco de trabajo que considera las líneas base de presión humana y los cambios de las presiones humanas con el tiempo y evaluamos a la efectividad de 338 AP en China entre 2010 y 2020. Consideramos el estado inicial de la presión humana en las AP como la línea base y analizamos los cambios en el índice de presión humana (IPH) bajo diferentes líneas base. Utilizamos modelos de bosque aleatorio para identificar las medidas de gestión que más aumentaron la efectividad de la resistencia a las presiones humanas en las AP con líneas base diferentes. Finalmente, analizamos con diferentes líneas base las relaciones entre los cambios en el IPH y los cambios en los ecosistemas naturales de las AP. De las AP con líneas base de IPH bajas, medianas y altas, 76.92% (n=150), 11.11% (n=12) y 22.86% (n=8), respectivamente, mostraron efectos positivos de resistencia a las presiones humanas. En general, si ignoramos las líneas base de las presiones humanas, se subestiman los efectos positivos de las AP de una u otra manera, especialmente aquellas con poca presión humana al inicio. En el caso de las AP que al inicio tienen diferentes presiones humanas, se deben tomar diferentes medidas de gestión para mejorar la efectividad y reducir las amenazas a los ecosistemas naturales. Creemos que nuestro marco de trabajo sirve para evaluar la efectividad mundial de las AP y recomendamos que se incluya en la Estrategia Post‐2020 de la Convención sobre la Diversidad Biológica.
Mejoría de la Efectividad de un Área Protegida al Considerar Diferentes Líneas Base de Presión Humana
摘要
自然保护地保护成效评估过去主要关注两个时间段之间人类压力的变化, 较少考虑自然保护地不同的人类压力基线(初始背景状态), 这可能会过高或过低估计自然保护地保护成效。我们提出了一个同时考虑人类压力基线和人类压力随时间变化的评估框架, 并评估了2010‐2020年中国338处自然保护地在不同基线下减缓人类压力的有效性。首先以人类压力的初始状态作为基线, 在不同基线下进一步分析了自然保护地内人类压力指数的变化;然后利用随机森林模型明确了对于不同基线的自然保护地提高其保护成效最重要的管理措施;最后进一步探讨了不同基线下人类压力指数变化与自然生态系统变化之间的关系。结果表明, 对于初始人类压力较低、中等和较高的自然保护地, 分别有76.92%、11.11%和22.86%在减缓人类压力方面表现出显著正效应。总体而言, 忽略人类压力基线在一定程度上低估了自然保护地的成效, 特别是对于初始人类压力较低的自然保护地。对于具有不同初始人类压力的自然保护地, 应采取不同的管理措施提高其保护成效并减少对自然生态系统的威胁。本研究提出的评估框架对评估全球自然保护地的保护成效具有重要作用, 我们建议将其纳入2020年后生物多样性战略目标的评估体系。
Whether rubber plantations have the role of water pumps in tropical Southeast Asia is under active debate. Fifteen years (1994–2008) of paired catchments water observation data and one year paired ...eddy covariance water flux data in primary tropical rain forest and tropical rubber plantation was used to clarify how rubber plantation affects local water resources of Xishuangbanna, China. Both catchment water observations and direct eddy covariance estimates indicates that more water was evapotranspired from rubber plantation (1137 mm based on catchment water balance, 1125 mm based on eddy covariance) than from the rain forest (969 mm based on catchment water balance, 927 mm based on eddy covariance). Soil water storage during the rainy season is not sufficient to maintain such high evapotranspiration rates, resulting in zero flow and water shortages during the dry season in the rubber plantation. Therefore, this study supports the idea that rubber plantations act as water pumps as suggested by local inhabitants.
Key Points
Two independent methods give the same results
More water was evapotranspirated by rubber plantation than rain forest
Rubber plantation do act as water pumps
PDF
