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Summary: PIWI-interacting RNAs (piRNAs) play a crucial role in safeguarding genome integrity by silencing mobile genetic elements. From flies to humans, piRNAs originate from long single-stranded precursors encoded by genomic piRNA clusters. How piRNA clusters form to adapt to genomic invaders and evolve to maintain protection remain key outstanding questions. Here, we generate a roadmap of piRNA clusters across seven species that highlights both similarities and variations. In mammals, we identify transcriptional readthrough as a mechanism to generate piRNAs from transposon insertions (piCs) downstream of genes (DoG). Together with the well-known stress-dependent DoG transcripts, our findings suggest a molecular mechanism for the formation of piRNA clusters in response to retroviral invasion. Finally, we identify a class of dynamic piRNA clusters in humans, underscoring unique features of human germ cell biology. Our results advance the understanding of conserved principles and species-specific variations in piRNA biology and provide tools for future studies.

Abstract Bisphosphonate-related osteonecrosis of jaw (BRONJ) is characterized by impaired osteogenic differentiation of orofacial bone marrow stromal cells (BMSCs). Corin has recently been demonstrated to act as a key regulator in bone development and orthopedic disorders. However, the role of corin in BRONJ-related BMSCs dysfunction remains unclarified. A m6A epitranscriptomic microarray study from our group shows that the CORIN gene is significantly upregulated and m6A hypermethylated during orofacial BMSCs osteogenic differentiation. Corin knockdown inhibits BMSCs osteogenic differentiation, whereas corin overexpression or soluble corin (sCorin) exerts a promotion effect. Furthermore, corin expression is negatively regulated by bisphosphonates (BPs). Corin overexpression or sCorin reverses BPs-impaired BMSCs differentiation ability. Mechanistically, we find altered expression of phos-ERK in corin knockdown/overexpression BMSCs and BMSCs under sCorin stimulation. PD98059 (a selective ERK inhibitor) blocks the corin-mediated promotion effect. With regard to the high methylation level of corin during osteogenic differentiation, we apply a non-selective m6A methylase inhibitor, Cycloleucine, which also blocks the corin-mediated promotion effect. Furthermore, we demonstrate that METTL7A modulates corin m6A modification and reverses BPs-impaired BMSCs function, indicating that METTL7A regulates corin expression and thus contributes to orofacial BMSCs differentiation ability. To conclude, our study reveals that corin reverses BPs-induced BMSCs dysfunction, and METTL7A-mediated corin m6A modification underlies corin promotion of osteogenic differentiation via the ERK pathway. We hope this brings new insights into future clinical treatments for BRONJ.

Bone grafting is crucial for bone regeneration. Recent studies have proposed the use of calcium citrate (CC) as a potential graft material. Notably, citrate does not inhibit hydroxyapatite (HAp) formation at specific calcium-to-citrate molar ratios. Octacalcium phosphate (OCP)/gelatine (Gel) composites, which are commonly produced from porcine Gel, are valued for their biodegradability and bone replacement capability. This study introduces fish Gel as an alternative to porcine Gel because of its wide acceptance and eco-friendliness. This is the first study to examine the interaction effects between two osteogenic materials, OCP/CC, and the influence of different gelatine matrix components on HAp formation in an SBF. Samples with varying CC contents were immersed in an SBF for 7 d and analysed using various techniques, confirming that high CC doses prevent HAp formation, whereas lower doses facilitate it. Notably, small-sized OCP/CC/porcine Gel composites exhibit a high HAp generation rate. Porcine Gel composites form denser HAp clusters, whereas fish Gel composites form larger spherical HAps. This suggests that lower CC doses not only avoid inhibiting HAp formation but also enhance it with the OCP/Gel composite. Compared with porcine Gel, fish Gel composites show less nucleation but an increased crystal growth for HAp.

Abstract The 1,900‐km‐long Sumatran fault plays an important role in accommodating oblique plate motion between the Indo‐Australian and Sunda plates. Although fault geometry, kinematics, and seismic activity are well‐studied, the onset of dextral motion on the Sumatran fault and uplift of adjacent Barisan Mountains is unclear; this hinders an understanding of the late Cenozoic evolution of Sumatra and the forearc region. In this study, we use low‐temperature thermochronology to measure cooling histories of rocks within and outside of the Sumatran fault. An accelerated exhumation within the fault zone began at ∼2 Ma. The Barisan Mountains may have experienced uplift and associated river incision in the late Miocene to Pliocene. The fault systems in the forearc region were inferred to be kinematically linked to the Andaman Sea and Sunda Strait and accommodated early relative plate convergence, then relocated the strike‐slip component of deformation to the Sumatran fault at ∼2 Ma.

Background: Programmed death receptor ligand 1 (PD-L1) is expressed at different levels in tumour tissues and tumour-infiltrating monocytes (TIMCs). The interpretation of PD-L1 expression in gastric cancer (GC) is more difficult because of its heterogeneity. Methods: The PD-L1 immunohistochemistry (IHC) by E1L3N assay was performed in GC tissues. The level and distributed characteristics of PD-L1 expression were observed to illustrate its heterogeneity both in the cancer tissues and TIMCs. The relationship between PD-L1 level and necrotic features of tumor cells, the number of TIMCs, the distribution of tertiary lymphoid tissue (TLS) in the stroma, and other clinicopathological factors were analysed. A Cox regression model was used to assess the prognostic value of PD-L1 expression. Results: Of the 110 GC samples, not only more cases (51/110 cases) could be detected by combined positive score (CPS) for PD-L1 expression compared the other two, tumour positive score (TPS), and mononuclear immune-cell density score (MIDS), but also there were more cases with the high level of PD-L1 expression by CPS, even if with good consistency among them (P < 0.05). The tumour cells with high expression of PD-L1 was prone to show a diffuse distributing, whereas mottled type in the low level. It was noteworthy that the strongly colored tumor cells tended to exhibit a mossy pattern which were distributed along the border between cancer nests and stroma, and the same pattern happened to occur in the positive mesenchymal cells contacting the tumor border, essentially lymphocytes and macrophages. The substantial necrosis in the tumour and the number of TIMCs was analyzed statistically significant correlated with CPS (P < 0.05), while other clinicopathological factors such as histological type, tumour size, invasion depth, TNM stage were uncorrelated. The number and distribution of TLS in the tumour and para-tumoural stroma indirectly affected PD-L1 in GC by associating with the quantity and pattern of TIMCs. Cox regression analysis revealed that the prognosis was poor when PD-L1 was positive. Conclusion: CPS is the best indicator for PD-L1 expression in GC, which tend to be increased expression following a large number of TIMCs and substantial tumour necrosis appeared. Heterogeneity was reflected in the different distributed pattern of PD-L1 expression, especially the mossy-like pantten of the staining tumor cell in the interface between tumour nests and stroma, regardless of the amount and intensity of PD-L1 expression. TLS is valuable for observing microscopic images to influence the quantity and pattern of TIMCs. CPS can be used as an independent prognostic factor for GC.

Abstract Background MicroRNAs have been recognized as critical regulators for the osteoblastic lineage differentiation of human adipose-derived stem cells (hASCs). Previously, we have displayed that silencing of miR-137 enhances the osteoblastic differentiation potential of hASCs partly through the coordination of lysine-specific histone demethylase 1 (LSD1), bone morphogenetic protein 2 (BMP2), and mothers against decapentaplegic homolog 4 (SMAD4). However, still numerous molecules involved in the osteogenic regulation of miR-137 remain unknown. This study aimed to further elucidate the epigenetic mechanisms of miR-137 on the osteogenic differentiation of hASCs. Methods Dual-luciferase reporter assay was performed to validate the binding to the 3′ untranslated region (3′ UTR) of NOTCH1 by miR-137. To further identify the role of NOTCH1 in miR-137-modulated osteogenesis, tangeretin (an inhibitor of NOTCH1) was applied to treat hASCs which were transfected with miR-137 knockdown lentiviruses, then together with negative control (NC), miR-137 overexpression and miR-137 knockdown groups, the osteogenic capacity and possible downstream signals were examined. Interrelationships between signaling pathways of NOTCH1-hairy and enhancer of split 1 (HES1), LSD1 and BMP2-SMADs were thoroughly investigated with separate knockdown of NOTCH1, LSD1, BMP2, and HES1. Results We confirmed that miR-137 directly targeted the 3′ UTR of NOTCH1 while positively regulated HES1. Tangeretin reversed the effects of miR-137 knockdown on osteogenic promotion and downstream genes expression. After knocking down NOTCH1 or BMP2 individually, we found that these two signals formed a positive feedback loop as well as activated LSD1 and HES1. In addition, LSD1 knockdown induced NOTCH1 expression while suppressed HES1. Conclusions Collectively, we proposed a NOTCH1/LSD1/BMP2 co-regulatory signaling network to elucidate the modulation of miR-137 on the osteoblastic differentiation of hASCs, thus providing mechanism-based rationale for miRNA-targeted therapy of bone defect.

AbstractCretaceous igneous rocks in SW Borneo are significant for investigating the Paleo-Pacific subduction and regional correlation. This paper presents new zircon ages and Sr–Nd–Pb–Hf–O isotopic and whole-rock geochemical data for the Cretaceous granitoids in the Schwaner Mountains. These granitoid samples yield formation ages of 92–80 Ma and can be geochemically subdivided into Group 1 biotite granite and granodiorite and Group 2 monzogranite. Group 1 has higher εHf t values of +1.2–+14.5 and lower δ18O values of 5.2–6.6‰ than Group 2 with εHf t and δ18O values of −1.5–+5.9 and 6.1–6.6‰, respectively. Group 1 samples show variable εNd t values of −1.9–+1.7, (206Pb/204Pb)i ratios of 18.63–19.29, (207Pb/204Pb)i ratios of 15.62–15.69, and (208Pb/204Pb)i ratios of 38.67–39.49 and are the products of partial melting of newly underplated mafic rocks with a component of crustal rocks. Group 2 with slightly negative εNd t values of −1.1–−1.5 was originated from partial melting of metasedimentary rocks with a juvenile mafic component. These granitoids were formed in a continental arc setting related to the Paleo-Pacific subduction during the Late Cretaceous and can compare with those contemporaneous I-type granites along the Kuching zone in NW Borneo. Those Late Cretaceous granitoids with A-type affinities from the easternmost Peninsular Malaysia and Singapore to the east of Sundaland might be formed in a back-arc extensional setting after the Paleo-Pacific subduction.

AbstractThe EW-trending Kuching zone in Borneo is a target region for exploring the southern continuation of Paleo-Pacific subduction from South China, Vietnam to SE Asia. Previous studies mainly focused on mafic igneous rocks, and poor attention has been paid to the contemporaneous granitoids in this zone. This study presented detailed zircon U-Pb geochronology and Lu-Hf isotope and whole-rock geochemistry analyses for late Cretaceous granitoids (granodiorites and granites) in the northern Kuching zone. These granitoids are dated at ~77.5-83.6 Ma with younger ages than the igneous rocks in the southern Kuching zone (~130-144 Ma). The granitoids have variable SiO2 (64.86-77.37 wt.%) and A/CNK (0.7-1.5) and are strongly enriched in LILE and depleted in HFSE with significant Ba, Nb, Sr, and Ti negative anomalies. They have variable (87Sr/86Sr)i (from 0.70656 to 0.71208), εNd(t) (from -4.4 to +0.9), and zircon εHf(t) (from -1.2 to +12.4) with high (206Pb/204Pb)i ratio of 18.78-19.74, suggesting derivation from a hybrid source involving meta-sedimentary and meta-igneous rocks. Combined with previously-published data, two episodes of Cretaceous (~77-98 Ma and ~130-144 Ma) magmatic activities are identified in the Kuching zone, showing a younging age trend from south to north. These episodes of Cretaceous igneous rocks and their spatial distribution in the Kuching zone can be totally comparable to those in South China and Vietnam. Thus, the Kuching zone was likely a part of the Paleo-Pacific subduction system during the Cretaceous, northerly linking to Vietnam and South China.

CD44 is a transmembrane protein that transduces extracellular stimuli to immune response. Neuroinflammation is a causative factor in neurodegenerative diseases, such as Parkinson’s disease (PD). Owing to its role in inflammation, this study investigated whether CD44 is involved in the pathological progression of PD. Our data showed that CD44 deficiency largely abolished proinflammatory cytokine expression in primary microglia and astrocytes. In PD model mice, CD44 knockout improved behavioral defects, prevented TH loss in the SNpc and striatum, and blocked activation of microglia and astrocytes. Moreover, CD44 neutralization by anti-CD44 antibody recapitulated the phenotypes observed in CD44 knockout mice. Mechanistically, CD44 neutralization blocked TLR4 expression and NF-κB p65 nuclear translocation induced by lipopolysaccharide in BV2 cells. Overall, our results indicate that CD44 deficiency has a beneficial role against PD, which is likely due to repression of the TLR4/NF-κB axis, leading to reduced neuroinflammation. Therefore, CD44 might be a therapeutic target for the development of anti-PD agents.

Although numerous land cover datasets can act as references for understanding land cover change in China, the inconsistencies between the datasets can also provide understanding. Previous studies on the consistency between land cover datasets have mostly focused on land cover type consistencies and have ignored data consistencies in land cover change. Therefore, we aim to analyse the consistencies in land cover changes through likelihood assessment methods. We compared the spatiotemporal changes in forest, grassland, cropland, and bare land in the Climate Change Initiative land cover dataset (CCI-LC), Moderate-resolution Resolution Imaging Spectroradiometer land cover dataset (MCD12Q1), China’s National Land Use and Cover Change (CNLUCC), Globeland30 and Global Land Cover Fine Surface Covering 30 (GLC-FCS30) datasets in 2010. The results showed that the percentages and changes in each land cover type in MCD12Q1 were different from those in the other datasets. For example, the proportion of grassland in MCD12Q1 was the highest, reaching 48.04%. The places with high consistency were the places where the land cover types were concentrated, and the bare land had the highest consistency. However, the consistency of China’s land cover change was quite low, and the percentage of low consistency was more than 87% from 2000-2018. Comparison of the data with the global artificial impervious area (GAIA) and Hansen-Global Forest Change (Hansen-GFC) datasets showed that the percentage of high construction gain consistency (38.83%) was higher than the forest change consistency, and the percentage forest loss high consistency (8.85%) was lower than the forest gain high consistency (12.76%). The results not only provide a basis for the use of land cover datasets but also give a clearer understanding of the pattern of land cover changes.

Pleomorphic adenomas (PAs) are the most common benign salivary neoplasms. PAs are generally slow-growing but may sometimes become aggressive and grow rapidly within a short period of time. Here, we report the case of an 83-year-old Chinese woman with an anterior neck mass that had been growing over the past 30 years. She felt uncomfortable because the mass had grown quite rapidly in the past year. The final diagnosis of a PA of the left submandibular gland was confirmed by histopathological and immunohistochemical examinations after surgical resection. Our patient recalled a history of an excision of a neck mass 40 years prior to presentation at another hospital. Based on our imaging findings and surgical findings, we speculate that the neck mass 40 years prior may also have been a PA. Our case reminds us the rare recurrence possibility of PAs, and early and thorough resection may have a good prognosis. In addition, to the best of our knowledge, this is the largest PA of the submandibular gland reported to date.

Renin-angiotensin system (RAS) inhibitors and calcium channel blockers (CCB) are often used together in chronic kidney disease (CKD). The PubMed, EMBASE, and Cochrane Library databases were searched to identify randomized controlled trials (RCTs) in order to explore better subtypes of CCB for the treatment of CKD. This meta-analysis of 12 RCTs with 967 CKD patients who were treated with RAS inhibitors demonstrated that, when compared with L-type CCB, N-/T-type CCB was superior in reducing urine albumin/protein excretion (SMD, −0.41; 95% CI, −0.64 to −0.18; p < 0.001) and aldosterone, without influencing serum creatinine (WMD, −3.64; 95% CI, −11.63 to 4.35; p = 0.37), glomerular filtration rate (SMD, 0.06; 95% CI, −0.13 to 0.25; p = 0.53), and adverse effects (RR, 0.95; 95% CI, 0.35 to 2.58; p = 0.93). In addition, N-/T-type CCB did not decrease the systolic blood pressure (BP) (WMD, 0.17; 95% CI, −1.05 to 1.39; p = 0.79) or diastolic BP (WMD, 0.64; 95% CI, −0.55 to 1.83; p = 0.29) when compared with L-type CCB. In CKD patients treated with RAS inhibitors, N-/T-type CCB is more effective than L-type CCB in reducing urine albumin/protein excretion without increased serum creatinine, decreased glomerular filtration rate, and increased adverse effects. The additional benefit is independent of BP and may be associated with decreased aldosterone (PROSPERO, CRD42020197560).

Abstract Background Tissue inflammation is an important problem in the field of human adipose-derived stem cell (ASC)-based therapeutic bone regeneration. Many studies indicate that inflammatory cytokines are disadvantageous for osteogenic differentiation and bone formation. Therefore, overcoming inflammation would be greatly beneficial in promoting ASC-mediated bone regeneration. The present study aims to investigate the potential anti-inflammatory role of Prostaglandin G/H synthase 1 (PTGS1) during the osteogenic differentiation of ASCs. Methods We performed TNFα treatment to investigate the response of PTGS1 to inflammation. Loss- and gain-of-function experiments were applied to investigate the function of PTGS1 in the osteogenic differentiation of ASCs ex vivo and in vivo. Western blot and confocal analyses were used to determine the molecular mechanism of PTGS1-regulated osteogenic differentiation. Results Our work demonstrates that PTGS1 expression is significantly increased upon inflammatory cytokine treatment. Both ex vivo and in vivo studies indicate that PTGS1 is required for the osteogenic differentiation of ASCs. Mechanistically, we show that PTGS1 regulates osteogenesis of ASCs via modulating the NF-κB signaling pathway. Conclusions Collectively, this work confirms that the PTGS1-NF-κB signaling pathway is a novel molecular target for ASC-mediated regenerative medicine.

Abstract New geochronological and geochemical data document a new and widely distributed succession of igneous and sedimentary rocks within the Sibumasu that extend from SW Yunnan through SE Asia as far as Sumatra. Our data revealed the presence of an Ordovician‐Silurian (mainly ∼490–430 Ma) igneous zone. The early Paleozoic granites in the zone display similar elemental and Sr–Nd–Pb–Hf isotopic compositions. They were derived from a common mixed source of ancient crustal materials with a juvenile component and formed in a subduction‐related setting. Detrital‐zircon U‐Pb apparent ages from the previously defined Precambrian Lancang and Ximeng units in the SW Yunnan portion of the Sibumasu are in the range of 3,306–428 Ma and 3,316–512 Ma, with the youngest age‐peaks of 505 Ma and 447 Ma, respectively, indicating the lower Paleozoic (Cambrian‐Silurian) sedimentary sequences. The Tarutao Unit and its equivalents in the SE Asia portion of the Sibumasu yield the U‐Pb apparent ages of 3,177–510 Ma, suggesting the maximum deposited time being Cambrian‐Ordovician. All these detrital zircon U‐Pb ages define two main peaks of ∼554–528 Ma and 964–905 Ma with εHf(t) values similar to those in the Qiangtang, Tethyan Himalaya, and eastern Indochina. The lower Paleozoic detritus in the Sibumasu were likely derived from the India‐Antarctica region of East Gondwana. We propose that the late Cambrian‐Silurian units formed in an outward‐propagating accretionary orogen in response to the consumption of the Prototethyan Ocean in SW Yunnan and SE Asia. Sibumasu might represent a part of the easterly migrating accretionary orogen along the northern margin of East Gondwana in the late Cambrian‐late Silurian.

Summary: It has been shown that histone deacetylase (HDAC) inhibitors hold considerable therapeutic potentials for treating neurodegeneration-related diseases including Parkinson disease (PD). Here, we synthesized an HDAC inhibitor named as HGC and examined its neuroprotective roles in PD models. Our results showed that HGC protects dopaminergic neurons from 1-methyl-4-phenylpyridinium (MPP+)-induced insults. Furthermore, in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced PD model mice, HGC application rectifies behavioral defects, improves tyrosine hydroxylase-positive neurons in the midbrain, and maintains mitochondrial integrity and functions. Mechanistically, mass spectrometry data revealed that HGC stimulates acetylation modification at lysine 28 of NDUFV1. Inhibition of HDAC6 by HGC is responsible for this acetylation modification. Functional tests showed that, as well as HGC, NDUFV1 exhibits beneficial roles against MPP+ injuries. Moreover, knockdown of NDUFV1 abolishes the neuroprotective roles of HGC. Taken together, our data indicate that HGC has a great therapeutic potential for treating PD and NDUFV1 might be a target for developing drugs against PD.

Abstract TGF‐β‐activated kinase 1 (TAK1), a serine/threonine kinase, is a key intermediate in several signaling pathways. However, its role in tumorigenesis is still not understood well. In this study, it is found that TAK1 expression decreases in esophageal tumor tissues and cell lines. In vitro experiments demonstrate that proliferation of esophageal tumor cells is enhanced by knockdown of TAK1 expression and attenuated by elevated expression of TAK1. Using a subcutaneous tumor model, these observations are confirmed in vivo. Based on the results from co‐immunoprecipitation coupled with mass spectrometry, Ras association domain family 9 (RASSF9) is identified as a downstream target of TAK1. TAK1 phosphorylates RASSF9 at S284, which leads to reduced RAS dimerization, thereby blocking RAF/MEK/ERK signal transduction. Clinical survey reveals that TAK1 expression is inversely correlated with survival in esophageal cancer patients. Taken together, the data reveal that TAK1‐mediated phosphorylation of RASSF9 at Ser284 negatively regulates esophageal tumor cell proliferation via inhibition of the RAS/MEK/ERK axis.

Abstract Like many important crops, peanut is a polyploid that underwent polyploidization, evolution, and domestication. The wild allotetraploid peanut species Arachis monticola (A. monticola) is an important and unique link from the wild diploid species to cultivated tetraploid species in the Arachis lineage. However, little is known about A. monticola and its role in the evolution and domestication of this important crop. A fully annotated sequence of ≈2.6 Gb A. monticola genome and comparative genomics of the Arachis species is reported. Genomic reconstruction of 17 wild diploids from AA, BB, EE, KK, and CC groups and 30 tetraploids demonstrates a monophyletic origin of A and B subgenomes in allotetraploid peanuts. The wild and cultivated tetraploids undergo asymmetric subgenome evolution, including homoeologous exchanges, homoeolog expression bias, and structural variation (SV), leading to subgenome functional divergence during peanut domestication. Significantly, SV‐associated homoeologs tend to show expression bias and correlation with pod size increase from diploids to wild and cultivated tetraploids. Moreover, genomic analysis of disease resistance genes shows the unique alleles present in the wild peanut can be introduced into breeding programs to improve some resistance traits in the cultivated peanuts. These genomic resources are valuable for studying polyploid genome evolution, domestication, and improvement of peanut production and resistance.

Abstract The thick Silurian siliciclastic sedimentary rocks in the Qin‐Fang region contrasting with their absence in surrounding regions have long been an enigma for the early Paleozoic geology of South China. Here we employ detrital zircon U‐Pb geochronology and Lu‐Hf isotope analysis of Cambrian to Devonian samples from the Qin‐Fang and adjacent regions to trace sedimentary provenance and to further constrain its tectonic setting. The similar age spectra of the Cambrian samples from both sides of the Qin‐Fang region imply that they should be derived from a common source(s), arguing against the presence of a Cambrian ocean in the Qin‐Fang region. However, the U‐Pb age patterns of these Cambrian samples, as well as from Silurian and Ordovician sandstones both from within and outside the Qin‐Fang region, differ significantly from those of a middle Devonian sample from the Qin‐Fang region, and Ordovician to upper Triassic samples from the Indochina Block. These results, in conjunction with regional geological information, indicate that the Yunkai Mountain, which is located adjacent to the Qin‐Fang region, must have been emerged above sea level in the middle Devonian. Meanwhile, it can also imply that the Qin‐Fang region should be a part of South China rather than being a segment of the Indochina Block. A two‐stage evolutionary history of the Qin‐Fang region is proposed, (1) an intracontinental basin mainly filled by materials eroded from east Gondwana and/or eastern Cathaysia Block during the early Paleozoic and (2) a foreland basin in the Yunkai Mountain region at least since the middle Devonian.

Abstract Background Mesenchymal stem cells (MSCs) are a reliable resource for bone regeneration and tissue engineering, but the molecular mechanisms of differentiation remain unclear. The tumor antigen 15-leucine-rich repeat containing membrane protein (LRRC15) is a transmembrane protein demonstrated to play important roles in cancer. However, little is known about its role in osteogenesis. This study was to evaluate the functions of LRRC15 in osteogenic differentiation of MSCs. Methods Osteogenic-induction treatment and the ovariectomized (OVX) model were performed to investigate the potential relationship between LRRC15 and MSC osteogenesis. A loss-of-function study was used to explore the functions of LRRC15 in osteogenic differentiation of MSCs in vitro and in vivo. NF-κB pathway inhibitor BAY117082, siRNA, nucleocytoplasmic separation, and ChIP assays were performed to clarify the molecular mechanism of LRRC15 in bone regulation. Results Our results first demonstrated that LRRC15 expression was upregulated upon osteogenic induction, and the level of LRRC15 was significantly decreased in OVX mice. Both in-vitro and in-vivo experiments detected that LRRC15 was required for osteogenesis of MSCs. Mechanistically, LRRC15 inhibited transcription factor NF-κB signaling by affecting the subcellular localization of p65. Further studies indicated that LRRC15 regulated osteogenic differentiation in a p65-dependent manner. Conclusions Taken together, our findings reveal that LRRC15 is an essential regulator for osteogenesis of MSCs through modulating p65 cytoplasmic/nuclear translocation, and give a novel hint for MSC-mediated bone regeneration.

Phytohormones regulate diverse aspects of plant growth and environmental responses. Recent high-throughput technologies have promoted a more comprehensive profiling of genes regulated by different hormones. However, these omics data generally result in large gene lists that make it challenging to interpret the data and extract insights into biological significance. With the rapid accumulation of theses large-scale experiments, especially the transcriptomic data available in public databases, a means of using this information to explore the transcriptional networks is needed. Different platforms have different architectures and designs, and even similar studies using the same platform may obtain data with large variances because of the highly dynamic and flexible effects of plant hormones; this makes it difficult to make comparisons across different studies and platforms. Here, we present a web server providing gene set-level analyses of Arabidopsis thaliana hormone responses. GSHR collected 333 RNA-seq and 1,205 microarray datasets from the Gene Expression Omnibus, characterizing transcriptomic changes in Arabidopsis in response to phytohormones including abscisic acid, auxin, brassinosteroids, cytokinins, ethylene, gibberellins, jasmonic acid, salicylic acid, and strigolactones. These data were further processed and organized into 1,368 gene sets regulated by different hormones or hormone-related factors. By comparing input gene lists to these gene sets, GSHR helped to identify gene sets from the input gene list regulated by different phytohormones or related factors. Together, GSHR links prior information regarding transcriptomic changes induced by hormones and related factors to newly generated data and facilities cross-study and cross-platform comparisons; this helps facilitate the mining of biologically significant information from large-scale datasets. The GSHR is freely available at http://bioinfo.sibs.ac.cn/GSHR/.

Mesenchymal stem cell (MSC)-mediated tissue engineering represents a promising strategy to address adipose tissue defects. MSCs derived from Wharton's jelly of the umbilical cord (WJCMSCs) may serve as an ideal source for adipose tissue engineering due to their abundance, safety profile, and accessibility. How to activate the directed differentiation potentials of WJCMSCs is the core point for their clinical applications. A thorough investigation of mechanisms involved in WJCMSC adipogenic differentiation is necessary to support their application in adipose tissue engineering and address shortcomings. Previous study showed, compared with periodontal ligament stem cells (PDLSCs), WJCMSCs had a weakened adipogenic differentiation potentials and lower expression of insulin-like growth factor binding protein 2 (IGFBP2). IGFBP2 may be involved in the adipogenesis of MSCs. Generally, IGFBP2 is involved in regulating biological activity of insulin-like growth factors, however, its functions in human MSCs are unclear. Here, we found IGFBP2 expression was upregulated upon adipogenic induction, and that IGFBP2 enhanced adipogenic differentiation of WJCMSCs and BMSCs. Moreover, IGFBP2 increased phosphorylation of c-Jun N-terminal kinase (p-JNK) and p-Akt, and activated JNK or Akt signaling significantly promoted adipogenic differentiation of MSCs. Furthermore, inhibitor-mediated blockage of either JNK or Akt signaling dramatically reduced IGFBP2-mediated adipogenic differentiation. And the JNK inhibitor, SP600125 markedly blocked IGFBP2-mediated Akt activation. Moreover, IGFBP2 was negatively regulated by BCOR, which inhibited adipogenic differentiation of WJCMSCs. Overall, our results reveal a new function of IGFBP2, providing a novel insight into the mechanism of adipogenic differentiation and identifying a potential target mediator for improving adipose tissue engineering based on WJCMSCs.

Due to their properties such as superparamagnetism, high surface area, large surface-to-volume ratio, easy separation under external magnetic fields, iron magnetic nanoparticles have attracted much attention in the past few decades. Various modification methods have been developed to produce biocompatible magnetic nanoparticles for protein immobilization. This review provides an updated and integrated focus on the fabrication and characterization of suitable magnetic iron nanoparticle-based nano-active materials for protein immobilization.

The tilapia (Oreochromis niloticus) skin hydrolysate was produced by thermal or enzymatic hydrolysis processes. Several product characteristics were studied such as the average molecular weight, 2,2-diphenyl-1-picrylhydrazyl radical-scavenging activity, yield, and protein content, in order to compare thermal hydrolysis and enzymatic proteolysis processes for the hydrolysed tilapia skin collagen production. The effects of the following hydrolysis parameters (retorting time and pH, protease combination, and proteolysis time) were studied. Compared with the thermal hydrolysis process, the enzymatic proteolysis process needed less time and milder conditions, under which hydrolysates could be obtained as low molecular weight antioxidant peptides.

Metalloproteases are emerging as useful agents in the treatment of many diseases including arthritis, cancer, cardiovascular diseases, and fibrosis. Studies that could shed light on the metalloprotease pharmaceutical applications require the pure enzyme. Here, we reported the structure-based design and synthesis of the affinity medium for the efficient purification of metalloprotease using the 4-aminophenylboronic acid (4-APBA) as affinity ligand, which was coupled with Sepharose 6B via cyanuric chloride as spacer. The molecular docking analysis showed that the boron atom was interacting with the hydroxyl group of Ser176 residue, whereas the hydroxyl group of the boronic moiety is oriented toward Leu175 and His177 residues. In addition to the covalent bond between the boron atom and hydroxyl group of Ser176, the spacer between boronic acid derivatives and medium beads contributes to the formation of an enzyme-medium complex. With this synthesized medium, we developed and optimized a one-step purification procedure and applied it for the affinity purification of metalloproteases from three commercial enzyme products. The native metalloproteases were purified to high homogeneity with more than 95% purity. The novel purification method developed in this work provides new opportunities for scientific, industrial and pharmaceutical projects.

The Jurassic igneous rocks on Sumatra Island are important for investigating the Mesotethyan evolution and regional correlation in Southeast Asia. This paper presents new laser ablation-multicollector-inductively coupled plasma-mass spectrometry zircon U-Pb-Hf geochronological and isotopic, whole-rock elemental, and Sr-Nd isotopic data for the newly identified Glebruk dolerite and andesite in North Sumatra. New zircon dating results suggest that these mafic-intermediate volcanic rocks, with ages of 150-146 Ma, were formed during the Late Jurassic. The Glebruk dolerite and andesite belong to the calc-alkaline series, are enriched in the light rare earth elements, and exhibit depletion in Nb, Ta, and Ti. Thus, they resemble arc-like volcanic rocks. They have low (87Sr/86Sr)i ratios of 0.7038-0.7048 and strong positive eNd(t) and eHf(t) values of +6.4 to +7.5 and +4.8 to +18.6, respectively. Their geochemical signatures suggest that these Late Jurassic volcanic rocks were derived from a depleted mantle wedge that was metasomatized by the slab-derived melts. The Glebruk volcanic rocks were formed in a continental arc setting in response to the Late Jurassic northward subduction of the Woyla Ocean beneath West Sumatra. Our results and regional geological observations suggest that the Mesotethyan subduction-related igneous rocks could extend from South Qiangtang through West Yunnan to North Sumatra. The Woyla Ocean could represent the southern extension of the Mesotethyan Ocean. [ABSTRACT FROM AUTHOR]