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There is a need for a detailed understanding of effective dietary interventions for children with obesity. This systematic review examined the effectiveness of diets of varying energy content as a component of weight treatment in children and adolescents with obesity, severe obesity and obesity-related comorbidity. A systematic search of six databases, from 2000 to 2021, for intervention studies of targeted dietary treatment for obesity in children aged 2-18 years identified 125 studies. Dietary interventions were grouped according to diet type and energy target. Risk of bias was assessed using the Effective Public Healthcare Panacea Project assessment tool. Meta-analysis examined change in body mass index (BMI) at intervention end. A broad array of diet types were effective at reducing BMI in children with obesity. When dietary types were considered by energy target, a gradient effect was observed. Very-low energy diets were most effective with a - 4.40 kg/m

According to the Paris Agreement signed on 12 December 2015, forests have great impact on controlling CO2 emissions. This study uses the nonoriented dynamic slack‐based data envelopment analysis model to evaluate the impact of a forestry area on the annual and overall energy efficiency in 28 EU countries during 2009‐2016. We found that annual and overall energy efficiency improved slightly and the energy efficiency in each country also changed when the forestry area was used as the output variable. Although the total energy consumption has declined slowly, CO2 emissions have not declined effectively. Thus, it will be challenging for the EU to meet its target of cutting CO2 emissions by 30% by 2030. All countries should take additional measures, such as energetically increasing forestry areas, optimally distributing the labor force among industries, and gradually replacing fossil fuels with renewable energy to improve their energy efficiency.

MORC family CW-type zinc finger 2 (MORC2), a GHKL-type ATPase, is aberrantly upregulated in multiple types of human tumors with profound effects on cancer aggressiveness, therapeutic resistance, and clinical outcome, thus making it an attractive drug target for anticancer therapy. However, the antagonists of MORC2 have not yet been documented.We report that MORC2 is a relatively stable protein, and the N-terminal homodimerization but not ATP binding and hydrolysis is crucial for its stability through immunoblotting analysis and Quantitative real-time PCR. The N-terminal but not C-terminal inhibitors of heat shock protein 90 (HSP90) destabilize MORC2 in multiple cancer cell lines, and strikingly, this process is independent on HSP90. Mechanistical investigations revealed that HSP90 N-terminal inhibitors disrupt MORC2 homodimer formation without affecting its ATPase activities, and promote its lysosomal degradation through the chaperone-mediated autophagy pathway. Consequently, HSP90 inhibitor 17-AAG effectively blocks the growth and metastatic potential of MORC2-expressing breast cancer cells both in vitro and in vivo, and these noted effects are not due to HSP90 inhibition.We uncover a previously unknown role for HSP90 N-terminal inhibitors in promoting MORC2 degradation in a HSP90-indepentent manner and support the potential application of these inhibitors for treating MORC2-overexpressing tumors, even those with low or absent HSP90 expression. These results also provide new clue for further design of novel small-molecule inhibitors of MORC2 for anticancer therapeutic application.

The structural characterization of sublayer surfaces of MIL-101 is reported by low-dose spherical aberration-corrected high-resolution transmission electron microscopy (HRTEM). The state-of-the-art microscopy directly images atomic/molecular configurations in thin crystals from charge density projections, and uncovers the structures of sublayer surfaces and their evolution to stable surfaces regulated by inorganic Cr3 (μ3 -O) trimers. This study provides compelling evidence of metal-organic frameworks (MOFs) crystal growth via the assembly of sublayer surfaces and has important implications in understanding the crystal growth and surface-related properties of MOFs.

BACKGROUND The fruiting body of Pleurotus tuoliensis deteriorates rapidly after harvest, causing a decline in its commercial value and a great reduction in its shelf life. According to the present research, carbohydrate-active enzymes (CAZymes) may cause the softening, liquefaction and autolysis of mature mushrooms after harvest. To further understand the in vivo molecular mechanism of CAZymes affecting the postharvest quality of P. tuoliensis fruiting bodies, a tandem mass tags labelling combined liquid chromatography-tandem mass spectrometry (TMT-MS/MS) proteomic analysis was performed on P. tuoliensis fruiting bodies during storage at 25 °C. RESULTS A total of 4737 proteins were identified, which had at least one unique peptide and had a confidence level above 95%. Consequently, 1307 differentially expressed proteins (DEPs) were recruited using the criteria of abundance fold change (FC) >1.5 or

Mitochondrial dysfunction is a fundamental pathological feature of Alzheimer's disease (AD). However, toxicity and poor brain enrichment of existing mitophagy inducers limit their further applications. In this study, a platform for AD therapy is developed using nanosized mesenchymal-stem-cells-derived extracellular vesicles with tyrosine phosphatase-2 (SHP2) high-expression (MSC-EVs-SHP2). The high blood-brain barrier penetration ability of MSC-EVs-SHP2 is demonstrated in AD-mice, facilitating SHP2 delivery to the brain. In addition, MSC-EVs-SHP2 significantly induces mitophagy of neuronal cells, which alleviates mitochondrial damage-mediated apoptosis and NLRP3 inflammasome activation. Mitophagy further diminishes neuronal cells apoptosis and neuroinflammation, culminating with rescued synaptic loss and cognitive decline in an AD mouse model. The EV-engineering technology provides a potential platform for effective AD therapy by inducing mitophagy.

BRCA1, a multifunctional protein with an important role in DNA double‐strand break repair by homologous recombination (HR), is subjected to ubiquitin‐dependent degradation. To date, several E3 ubiquitin ligases have been identified to govern BRCA1 stability, but the deubiquitinase that counteracts its turnover remains undefined. In this study, we report that the ubiquitin‐specific protease 9X (USP9X) is a bona fide deubiquitinase for BRCA1 in human cancer cells. Reciprocal immunoprecipitation assays demonstrated that USP9X interacted with BRCA1. Depletion of USP9X by short interfering RNAs or inhibition of USP9X by the small‐molecular inhibitor WP1130 significantly reduced BRCA1 protein abundance, without affecting its mRNA levels. In contrast, overexpression of wild‐type USP9X, but not its deubiquitinase activity‐defective mutant (C1566S), resulted in an upregulation of BRCA1 protein levels. Moreover, USP9X depletion reduced the half‐life of BRCA1, accompanied by an increase in its ubiquitination. HR assays showed that knockdown of USP9X significantly reduced HR efficiency, which was partially rescued by reintroduction of BRCA1 into USP9X‐depleted cells. In support of these findings, USP9X knockdown significantly enhanced sensitivity to PARP inhibitor Olaparib and methyl methanesulfonate (MMS). Collectively, these results establish USP9X as a deubiquitinase for BRCA1 and reveal a previously unrecognized role of USP9X in the regulation of HR repair and the sensitivity of cancer cells to DNA‐damaging agents., In this study, we identified USP9X as the first deubiquitinase of BRCA1. Consequently, USP9X regulates BRCA1‐mediated HR repair and confers resistance to DNA‐damaging agents in human cancer cells.

Summary Mitochondria not only supply the energy for cell function, but also take part in cell signaling. This review describes the dysfunctions of mitochondria in aging and neurodegenerative diseases, and the signaling pathways leading to mitochondrial biogenesis (including PGC‐1 family proteins, SIRT1, AMPK) and mitophagy (parkin‐Pink1 pathway). Understanding the regulation of these mitochondrial pathways may be beneficial in finding pharmacological approaches or lifestyle changes (caloric restrict or exercise) to modulate mitochondrial biogenesis and/or to activate mitophagy for the removal of damaged mitochondria, thus reducing the onset and/or severity of neurodegenerative diseases.

Pregnancy‐specific glycoprotein 9 (PSG9) is a placental glycoprotein essential for the maintenance of normal gestation in mammals. Bioinformatics analysis of multiple publicly available datasets revealed aberrant PSG9 expression in breast tumors, but its functional and mechanistic role in breast cancer remains unexplored. Here, we report that PSG9 expression levels were elevated in tumor tissues and plasma specimens from breast cancer patients, and were associated with poor prognosis. Gain‐ or loss‐of‐function studies demonstrated that PSG9 promoted breast cancer cell proliferation, migration, and invasionin vitro, and enhanced tumor growth and lung colonization in vivo. Mechanistically, transforming growth factor‐β1 (TGF‐β1) transcriptionally activated PSG9 expression through enhancing the enrichment of Smad3 and Smad4 onto PSG9 promoter regions containing two putative Smad‐binding elements (SBEs). Mutation of both SBEs in the PSG9 promoter, or knockdown of TGF‐β receptor 1 (TGFBR1), TGFBR2, Smad3, or Smad4 impaired the ability of TGF‐β1 to induce PSG9 expression. Consequently, PSG9 contributed to TGF‐β1‐induced epithelial‐mesenchymal transition (EMT) and breast cancer cell migration and invasion. Moreover, PSG9 enhanced the stability of Smad2, Smad3, and Smad4 proteins by blocking their proteasomal degradation, and regulated the expression of TGF‐β1 target genes involved in EMT and breast cancer progression, thus further amplifying the canonical TGF‐β/Smad signaling in breast cancer cells. Collectively, these findings establish PSG9 as a novel player in breast cancer progressionvia hijacking the canonical TGF‐β/Smad signaling, and identify PSG9 as a potential plasma biomarker for the early detection of breast cancer., Our findings establish PSG9 as a novel player in breast cancer progression via hijacking the canonical TGF‐β/Smad signaling and identify PSG9 as a potential plasma biomarker for the early detection of breast cancer.

The aim of this study was to develop an effective one‐step decoloration and deproteinisation method using macroporous resin for Cordyceps militaris polysaccharide (CMP) extraction. Performances of different resins were compared, and the structures and bioactivities of CMP recovered using this one‐step method were evaluated and compared with traditional methods. The results showed that NKA‐9 resin exhibited the highest adsorption capacity for pigment and free protein than other tested resins. Under the optimised condition, NKA‐9 resin adsorption exhibited high decoloration ratio (80.69%), deproteinisation ratio (62.51%) and polysaccharide recovery ratio (78.08%). Furthermore spectroscopic analysis revealed that the structure of CMP remained unchanged after adsorption, but some reagent residues can be detected using traditional methods. Compared with traditional methods, the antioxidant activity of CMP extracted using a one‐step method was significantly higher, without negative impact on cell viability. Thus, this novel technique is a promising alternative method for CMP separation and purification.

The age-related functional exhaustion limits potential efficacy of mesenchymal stem cells (MSC) in treating cardiovascular disease. Therefore, rejuvenation of aged MSC in the elderly population is of great interest. We have previously reported that Erb-B2 receptor tyrosine kinase 4 ( ERBB4) plays a critical role in regulating MSC survival under hypoxia. The aim of this study was to investigate whether ERBB4 rejuvenates aged MSC and how ERBB4 enhances therapeutic efficacy of aged MSC in treating myocardial infarction (MI). Compared with vector aged MSC (aged-MSC), ERBB4-engineered aged MSC (ER4-aged-MSC) conferred resistance to oxidative stress-induced cell death and ameliorated the senescent phenotype in vitro. Four weeks after MI, the ER4-aged-MSC group exhibited enhanced blood vessel density, reduced cardiac remodeling and apoptosis with improved heart function compared with the aged-MSC group. Overexpression of ERBB4 caused an increase in phosphorylated v-akt murine thymoma viral oncogene homolog 1 (AKT), and phosphorylated ERK expression under hypoxia. ER4-aged-MSC secreted higher levels of angiopoietin, epithelial neutrophil activating peptide 78, VEGF, and fibroblast growth factor 2, and enhanced tube formation in HUVEC. The impact of ERBB4 on protein expression, proangiogenesis, cell behavior, and cytokine secretion was abolished by inhibiting PI3K/AKT and MAPK/ERK signaling pathway.-Liang, X., Ding, Y., Lin, F., Zhang, Y., Zhou, X., Meng, Q., Lu, X., Jiang, G., Zhu, H., Chen, Y., Lian, Q., Fan, H., Liu, Z. Overexpression of ERBB4 rejuvenates aged mesenchymal stem cells and enhances angiogenesis via PI3K/AKT and MAPK/ERK pathways.

Two pairs of novel chiral chromium lanthanide compounds, formulated as l- and d-[Gd4 Cr4 (IN)10 (μ3 -OH)4 (μ4 -O)4 (H2 O)12 ]⋅[IN]2 ⋅8 H2 O (1 and 3), and l- and d-[Dy4 Cr4 (IN)11 (μ3 -OH)4 (μ4 -O)4 (H2 O)8 ]⋅[IN]⋅1.5 H2 O (2 and 4) (HIN=isonicotinic acid) have been successfully synthesized and characterized. Structural analysis reveals that four Ln3+ ions and four Cr3+ ions connect with each other and yield a "tower-like" [Ln4 Cr4 ] skeleton. Apart from the above featuring an aesthetically charming structure, circular dichroism (CD) spectra confirm that compounds 1 and 3, 2 and 4 are enantiomers. To the best of our knowledge, these are the largest chiral chromium lanthanide compounds. In addition, magnetic interaction shows that Gd (the mixture of 1 and 3) exhibits significant cryogenic magnetocaloric effect (MCE) with -ΔSm =18.08 J kg-1 K-1 (34.69 mJ cm-3 K-1 ). Also, the observed second-harmonic generation efficiencies of [Gd4 Cr4 (IN)10 (μ3 -OH)4 (μ4 -O)4 (H2 O)12 ]⋅[IN]2 ⋅8 H2 O and [Dy4 Cr4 (IN)11 (μ3 -OH)4 (μ4 -O)4 (H2 O)8 ]⋅[IN]⋅1.5 H2 O are 0.3 and 0.4 times that of urea, respectively.