BPO-promoted [4 + 2] cyclization of enaminones and o-phenylenediamines to 2-acyl quinoxalines via a cascade transamination and C-H amination.

Rapid assembly of quinoxalines in a single step from readily available precursors has been recognized as an ideal platform in terms of efficiency and operation. Herein, we report a BPO-promoted metal-free approach to 2-acyl quinoxalines from enaminones and o-phenylenediamines via cascade transamination and C-H amination. This methodology demonstrates excellent compatibility with various substrates, including o-hydroxy enaminones, drug derivatives and natural products under mild reaction conditions.

Skeletal stem cells: origins, definitions, and functions in bone development and disease.

Skeletal stem cells (SSCs) are tissue-specific stem cells that can self-renew and sit at the apex of their differentiation hierarchy, giving rise to mature skeletal cell types required for bone growth, maintenance, and repair. Dysfunction in SSCs is caused by stress conditions like ageing and inflammation and is emerging as a contributor to skeletal pathology, such as the pathogenesis of fracture nonunion. Recent lineage tracing experiments have shown that SSCs exist in the bone marrow, periosteum, and resting zone of the growth plate. Unraveling their regulatory networks is crucial for understanding skeletal diseases and developing therapeutic strategies. In this review, we systematically introduce the definition, location, stem cell niches, regulatory signaling pathways, and clinical applications of SSCs.

Histone demethylase LSD1 is critical for endochondral ossification during bone fracture healing.

Bone fracture is repaired predominantly through endochondral ossification. However, the regulation of endochondral ossification by key factors during fracture healing remains largely enigmatic. Here, we identify histone modification enzyme LSD1 as a critical factor regulating endochondral ossification during bone regeneration. Loss of LSD1 in Prx1 lineage cells severely impaired bone fracture healing. Mechanistically, LSD1 tightly controls retinoic acid signaling through regulation of Aldh1a2 expression level. The increased retinoic acid signaling in LSD1-deficient mice suppressed SOX9 expression and impeded the cartilaginous callus formation during fracture repair. The discovery that LSD1 can regulate endochondral ossification during fracture healing will benefit the understanding of bone regeneration and have implications for regenerative medicine.

Tendon-derived cathepsin K-expressing progenitor cells activate Hedgehog signaling to drive heterotopic ossification.

Heterotopic ossification (HO) is pathological bone formation characterized by ossification within muscle, tendons, or other soft tissues. However, the cells of origin and mechanisms involved in the pathogenesis of HO remain elusive. Here we show that deletion of suppressor of fused (Sufu) in cathepsin K-Cre-expressing (Ctsk-Cre-expressing) cells resulted in spontaneous and progressive ligament, tendon, and periarticular ossification. Lineage tracing studies and cell functional analysis demonstrated that Ctsk-Cre could label a subpopulation of tendon-derived progenitor cells (TDPCs) marked by the tendon marker Scleraxis (Scx). Ctsk+Scx+ TDPCs are enriched for tendon stem cell markers and show the highest self-renewal capacity and differentiation potential. Sufu deficiency caused enhanced chondrogenic and osteogenic differentiation of Ctsk-Cre-expressing tendon-derived cells via upregulation of Hedgehog (Hh) signaling. Furthermore, pharmacological intervention in Hh signaling using JQ1 suppressed the development of HO. Thus, our results show that Ctsk-Cre labels a subpopulation of TDPCs contributing to HO and that their cell-fate changes are driven by activation of Hh signaling.

Simultaneous determination of multi-allergens in surimi products by LC-MS/MS with a stable isotope-labeled peptide.

A novel LC-MS/MS method for simultaneous quantification of the allergens of soy, milk and egg in surimi products was established based on three signature peptides, namely EAFGVNMQIVR (soy glycinin G2), YLGYLEQLLR (milk α-S1-casein), GGLEPINFQTAADQAR (egg ovalbumin) and a stable isotope-labeled peptide EAFGVNMQI* (I*, 13C6, 15N) VR. After protein extraction and tryptic digestion, four selected marker peptides were measured by HPLC-MS/MS. The determination coefficient R2 was higher than 0.9914 at the range of 0.5-200 ng/mL and both the intra and interday precision RSD were less than 6.7% for three peptides. Limit of quantitation was shown as 0.054 µg/g for soy, 0.024 µg/g for milk and 0.032 µg/g for egg. Current validated method was successfully applied to analyze surimi products, which can not only provide accurate quantification information of allergens for sensitive consumers, but also it may be used for label management for surimi market.

The Undervalued Effects of Polychlorinated Biphenyl Exposure on Breast Cancer.

The incidence of breast cancer across the world has been on the rise in recent decades. Because identified risk factors can only explain a relatively small portion of the cases, environmental exposure to organic pollutants is suspected to play a role in breast cancer etiology. Polychlorinated biphenyls (PCBs) are among the most abundant pollutants, and the impact of their exposure on breast cancer risk has been extensively studied in recent decades. However, the results of most epidemiologic studies do not support an association between PCB exposure and breast cancer risk. We hypothesized that the effects of PCBs on breast cancer might have been undervalued for reasons such as insufficient recognition of the confounding effects of several factors and lack of attention on the innate heterogeneity of PCB mixtures or breast cancer. After reviewing the evidence in the existing literature, we concluded that early life exposure, known risk factors of breast cancer, and impact of exposure to other pollutants are the main sources of confounding effects and have potentially masked the associations between PCBs and breast cancer. Because PCBs are mixtures of congeners with varied properties, and because breast cancers of different subtypes are etiologically distinct diseases, the absence of stratified subgroup analysis on individual PCBs and patients with specific biological subtypes and insufficient attention paid to the results of these subgroup analyses may result in an underestimation of the correlations between PCBs and breast cancer. In future studies, these factors must be taken into consideration when exploring the effect of PCB exposure on breast cancer risk.

Epidemiological survey on a family aggregation COVID-19 in Y County, Chenzhou City, Hunan / 上海预防医学

Objective To investigate epidemic characteristics of a family aggregation COVID-19, and to provide scientific basis for prevention and control of family aggregation epidemic. Methods] Field epidemiological methods were used to investigate the cases and close contacts of a family aggregation COVID-19 in Y County, Chenzhou City, Hunan Province. Descriptive statistical analysis was used on epidemiological data . The 2019-nCoV nucleic acid was detected by real-time fluorescence quantitative RT-PCR. Results It was found that Ms. Deng was infected with COVID-19 and became the infectious source of the family aggregation epidemic , who had lived in Wuhan Hubei Province. Her boyfriend Mr. Cao became a second-generation case of COVID-19..Another two asymptomatic but infected persons were family members living with Ms.Deng . Conclusion COVID-19 easily spreads within families. The awareness of family members' protection, the education of new coronavirus pneumonia prevention and control in key groups should be strengthened to avoid the occurrence and spread of family aggregation epidemic.

The Significant Impact of Carbon Nanotubes on the Electrochemical Reactivity of Mg-Bearing Metallic Glasses with High Compressive Strength.

Here, we elucidate the significant impact of carbon nanotubes (CNTs) on the electrochemical behavior of Mg-based amorphous composite materials that were reinforced with CNTs while using pressure die casting. The addition of 3 vol % CNTs led to an increase in the compressive strength of Mg-based amorphous material from 812 MPa to 1007 MPa, and the fracture strain from 1.91% to 2.67% in the composite. Interestingly, the addition of CNTs significantly contributed to the enhancement of corrosion resistance of Mg-based glass by ~30%. The superior mechanical properties are primarily related to the fact that the addition of CNTs hindered the growth of shear bands (cracks), while the high corrosion resistance is related to inferior wettability and the bridging effect between adherent corrosive oxide film and the matrix that provided enhanced corrosion resistance.

Lkb1 deletion in periosteal mesenchymal progenitors induces osteogenic tumors through mTORC1 activation.

Bone osteogenic sarcoma has a poor prognosis as the exact cell of origin and the signaling pathways underling tumor formation remain undefined. Here, we report an osteogenic tumor mouse model based on the conditional knockout of liver kinase b1 (Lkb1; also known as Stk11) in Cathepsin K (Ctsk)-Cre expressing cells. Lineage tracing studies demonstrated that Ctsk-Cre could label a population of periosteal cells. The cells functioned as mesenchymal progenitors with regard to markers and functional properties. LKB1 deficiency increased proliferation and osteoblast differentiation of Ctsk+ periosteal cells, while downregulation of mTORC1 activity, using Raptor genetic mouse model or mTORC1 inhibitor treatment, ameliorated tumor progression of Ctsk-Cre Lkb1fllfl mice. Xenograft mouse models, using human osteosarcoma cell lines, also demonstrated that LKB1 deficiency promoted tumor formation, while mTOR inhibition suppressed xenograft tumor growth. In summary, we identified periosteum-derived Ctsk-Cre expressing cells as a cell of origin for osteogenic tumor and suggested the LKB1-mTORC1 pathway as a promising target for treatment of osteogenic tumor.

Toward a unified model for predicting color quality of light sources.

Considering that the existing color quality (CQ) metrics for light sources cannot correlate well with the subjective evaluation, in an immersive environment equipped with a multichannel LED light source, a psychophysical experiment by categorical judgment method was carried out to assess the three perception-related CQ attributes of light sources in terms of naturalness, colorfulness, and preference. The experiment collected the subjective responses to these attributes of up to 41 metameric spectra at each of four test correlated color temperatures (CCTs) ranging from 2800 to 6500 K, which covers the usual white-light range for general lighting. The results indicate that preference exhibits relatively high correlation with naturalness and colorfulness, and naturalness is weakly related to colorfulness. Besides, 20 typical CQ metrics were adopted to examine their validity in characterizing the subjective data, confirming their limited performance. Meanwhile, the underlying relationship of these metrics and the subjective data was also analyzed by the multidimensional scaling, revealing that almost all metrics can correspond to one attribute of naturalness, colorfulness, and preference, and that the saturation level is identified as a critical factor affecting these attributes. Based on these results, a unified CQ model was developed with a multiple nonlinear regression equation combining the Illuminating Engineering Society of North America color rendition method. The model accords satisfactorily with the subjective evaluation, while being applicable to a wide range of CCTs.

SMURF2 regulates bone homeostasis by disrupting SMAD3 interaction with vitamin D receptor in osteoblasts.

Coordination between osteoblasts and osteoclasts is required for bone health and homeostasis. Here we show that mice deficient in SMURF2 have severe osteoporosis in vivo. This low bone mass phenotype is accompanied by a pronounced increase in osteoclast numbers, although Smurf2-deficient osteoclasts have no intrinsic alterations in activity. Smurf2-deficient osteoblasts display increased expression of RANKL, the central osteoclastogenic cytokine. Mechanistically, SMURF2 regulates RANKL expression by disrupting the interaction between SMAD3 and vitamin D receptor by altering SMAD3 ubiquitination. Selective deletion of Smurf2 in the osteoblast lineage recapitulates the phenotype of germline Smurf2-deficient mice, indicating that SMURF2 regulates osteoblast-dependent osteoclast activity rather than directly affecting the osteoclast. Our results reveal SMURF2 as an important regulator of the critical communication between osteoblasts and osteoclasts. Furthermore, the bone mass phenotype in Smurf2- and Smurf1-deficient mice is opposite, indicating that SMURF2 has a non-overlapping and, in some respects, opposite function to SMURF1.

Biomechanics of osteonecrosis of femoral head after tantalum rod implantation: a three-dimensional finite element analysis / 中国组织工程研究

BACKGROUND: The femoral anterolateral column plays a key role in hip preservation surgery, and the China-Japan Friendship Hospital (CJFH) type stresses the anterolateral column, but there is little information available in three-dimensional (3D) finite element analysis of the L-type tantalum rod implantation.OBJECTIVE: To establish a 3D finite element model of L-type tantalum rod implantation into the normal, necrotic and L-type necrotic areas, followed by a finite element analysis, and to explore the importance of the integrity of the anterolateral column for hip preservation surgery, thus providing biomechanical evidence for the treatment of CJFH type.METHODS: Based on the prepared 3D models of CJFH L1, L2 and L3 osteonecrosis of the femoral head (ONFH) and normal hip, the 3D finite element model of tantalum rod implantation of femoral head necrosis was established, and finite element analysis was conducted. The stress distribution and the maximum Mises stress value of cortical shell of normal femoral head, necrotic femoral head and tantalum rod implanted ONFH were observed and compared.RESULTS AND CONCLUSION: (1) The maximum Mises of the weight-bearing area of cortical bone shell of L-type ONGH was higher than that of normal femoral, L1. L2 and L3 increased by 21.76%, 31.02%, and 42.79%, respectively. (2) The maximum Mises of weight-bearing area of cortical bone shell was decreased after tantalum rod implantation, L1 L2 and L3 decreased by 13.38%, 8.81%, and 11.45%, respectively. (3) In necrotic femoral head, the decreased bearing stress, leads to stress concentration on the femoral head bone shell, so the maximum is higher than that of the normal condition. The higher classification is, the greater the stress concentration of the cortical bone shell is. Tantalum rod implantation share certain stress. (4) Tantalum rod implantation corrects some stresses of the bone shell of ONFH, and can prevent collapse and exert the biomechanical effect of supporting subchondral bone. Furthermore, the integrity of the lateral column of the necrotic femoral head affects the efficacy of hip preservation, and more lateral column preserved always accompanied with better hip preservation. The higher CJFH classification exhibits a higher risk of collapse, and poorer hip preservation.