Construction of AlGaN/GaN high-electron-mobility transistor-based biosensor for ultrasensitive detection of SARS-CoV-2 spike proteins and virions.

The COVID-19 pandemic has highlighted the need for rapid and sensitive detection of SARS-CoV-2. Here, we report an ultrasensitive SARS-CoV-2 immunosensor by integration of an AlGaN/GaN high-electron-mobility transistor (HEMT) and anti-SARS-CoV-2 spike protein antibody. The AlGaN/GaN HEMT immunosensor has demonstrated the capability to detect SARS-CoV-2 spike proteins at an impressively low concentration of 10-22 M. The sensor was also applied to pseudoviruses and SARS-CoV-2 ΔN virions that display the Spike proteins with a single virion particle sensitivity. These features validate the potential of AlGaN/GaN HEMT biosensors for point of care tests targeting SARS-CoV-2. This research not only provides the first HEMT biosensing platform for ultrasensitive and label-free detection of SARS-CoV-2.

Near Infrared Responsive Gold Nanorods Attenuate Osteoarthritis Progression by Targeting TRPV1.

Osteoarthritis (OA) is the most common degenerative joint disease worldwide, with the main pathological manifestation of articular cartilage degeneration. It have been investigated that pharmacological activation of transient receptor potential vanilloid 1 (TRPV1) significantly alleviated cartilage degeneration by abolishing chondrocyte ferroptosis. In this work, in view of the thermal activated feature of TRPV1, Citrate-stabilized gold nanorods (Cit-AuNRs) is conjugated to TRPV1 monoclonal antibody (Cit-AuNRs@Anti-TRPV1) as a photothermal switch for TRPV1 activation in chondrocytes under near infrared (NIR) irradiation. The conjugation of TRPV1 monoclonal antibody barely affect the morphology and physicochemical properties of Cit-AuNRs. Under NIR irradiation, Cit-AuNRs@Anti-TRPV1 exhibited good biocompatibility and flexible photothermal responsiveness. Intra-articular injection of Cit-AuNRs@Anti-TRPV1 followed by NIR irradiation significantly activated TRPV1 and attenuated cartilage degradation by suppressing chondrocytes ferroptosis. The osteophyte formation and subchondral bone sclerosis are remarkably alleviated by NIR-inspired Cit-AuNRs@Anti-TRPV1. Furthermore, the activation of TRPV1 by Cit-AuNRs@Anti-TRPV1 evidently improved physical activities and alleviated pain of destabilization of the medial meniscus (DMM)-induced OA mice. The study reveals Cit-AuNRs@Anti-TRPV1 under NIR irradiation protects chondrocytes from ferroptosis and attenuates OA progression, providing a potential therapeutic strategy for the treatment of OA.

XJB-5-131 protects chondrocytes from ferroptosis to alleviate osteoarthritis progression via restoring Pebp1 expression.

Background: Osteoarthritis (OA) is the most common age-related musculoskeletal disease. However, there is still a lack of therapy that can modify OA progression due to the complex pathogenic mechanisms. The aim of the study was to explore the role and mechanism of XJB-5-131 inhibiting chondrocytes ferroptosis to alleviate OA progression. Methods: We treated tert-butyl hydroperoxide (TBHP)-induced ferroptosis of mouse primary chondrocytes with XJB-5-131 in vitro. The intracellular ferroptotic hallmarks, cartilage anabolic and catabolic markers, ferroptosis regulatory genes and proteins were detected. Then we established a mouse OA model via destabilization of the medial meniscus (DMM) surgery. The OA mice were treated with intra-articular injection of XJB-5-131 regularly (2 µM, 3 times per week). After 4 and 8 weeks, we performed micro-CT and histological examination to evaluate the protection role of XJB-5-131 in mouse OA subjects. RNA sequencing analysis was performed to unveil the key downstream gene of XJB-5-131 exerting the anti-ferroptotic effect in OA. Results: XJB-5-131 significantly suppressed TBHP-induced increases of ferroptotic hallmarks (ROS, lipid peroxidation, and Fe2+ accumulation), ferroptotic drivers (Ptgs2, Pgd, Tfrc, Atf3, Cdo1), while restored the expression of ferroptotic suppressors (Gpx4, Fth1). XJB-5-131 evidently promoted the expression of cartilage anabolic and decreased the expression of cartilage catabolic markers. Moreover, intra-articular injection of XJB-5-131 significantly inhibited the expression of Cox2 and Mmp13, while promoted the expression of Col2a1, Gpx4 and Fth1 in DMM-induced mouse articular cartilage. Further, we identified Pebp1 as a potential target of XJB-5-131 by RNA sequencing analysis. The anti-ferroptosis and chondroprotective effects of XJB-5-131 were significantly diminished by Locostatin, a specific antagonist of Pebp1. Conclusion: XJB-5-131 significantly protects chondrocytes from ferroptosis in TBHP-induced mouse primary chondrocytes and DMM surgery-induced OA mice model via restoring the expression of Pebp1. XJB-5-131 is a potential therapeutic drug in the management of OA progression.

Non-volatile rippled-assisted optoelectronic array for all-day motion detection and recognition.

In-sensor processing has the potential to reduce the energy consumption and hardware complexity of motion detection and recognition. However, the state-of-the-art all-in-one array integration technologies with simultaneous broadband spectrum image capture (sensory), image memory (storage) and image processing (computation) functions are still insufficient. Here, macroscale (2 × 2 mm2) integration of a rippled-assisted optoelectronic array (18 × 18 pixels) for all-day motion detection and recognition. The rippled-assisted optoelectronic array exhibits remarkable uniformity in the memory window, optically stimulated non-volatile positive and negative photoconductance. Importantly, the array achieves an extensive optical storage dynamic range exceeding 106, and exceptionally high room-temperature mobility up to 406.7 cm2 V-1 s-1, four times higher than the International Roadmap for Device and Systems 2028 target. Additionally, the spectral range of each rippled-assisted optoelectronic processor covers visible to near-infrared (405 nm-940 nm), achieving function of motion detection and recognition.

Text analysis of Macao's COVID-19 prevention and control policies: discussion on strategy evolution and public health capabilities.

Background: The global impact of the coronavirus disease 2019 (COVID-19) pandemic has been profound. Macao Special Administrative Region (SAR), renowned as an international hub for tourism and entertainment, has actively responded to the crisis. However, a comprehensive analysis detailing the evolution of Macao SAR's policies throughout this period is currently lacking. Methods: This study aims to comprehensively understand the decision-making processes, policy formulation, and implementation strategies of the Macao SAR government amidst the pandemic through the analysis of speeches and inquiries made by legislative council members and other relevant documents. Employing both quantitative and qualitative analytical methods, including word frequency analysis and word vector models, we identify key themes and patterns. Additionally, we conducted a comparative analysis of keyword frequencies during the two waves of the pandemic using radar charts. Results: The results indicate a heightened focus by the Macao SAR government on pandemic control measures and economic impacts. In response, the government formulated and implemented policies, provided support initiatives, and managed port clearance, all while focusing on enhancing healthcare infrastructure and community services. Conclusions: The government persistently amends its policies in response to the evolving challenges posed by the pandemic. The evolution of the dynamic Zero-COVID strategy highlights the government's adaptability and comprehensive consideration, ensuring public health and societal stability.

Reinvestigation on the Mechanism for Algae Inactivation by the Ultraviolet/Peracetic Acid Process: Role of Reactive Species and Performance in Natural Water.

This study provided an in-depth understanding of enhanced algae inactivation by combining ultraviolet and peracetic acid (UV/PAA) and selecting Microcystis aeruginosa as the target algae species. The electron paramagnetic resonance (EPR) tests and scavenging experiments provided direct evidence on the formed reactive species (RSs) and indicated the dominant role of RSs including singlet oxygen (1O2) and hydroxyl (HO•) and organic (RO•) radicals in algae inactivation. Based on the algae inactivation kinetic model and the determined steady-state concentration of RSs, the contribution of RSs was quantitatively assessed with the second-order rate constants for the inactivation of algae by HO•, RO•, and 1O2 of 2.67 × 109, 3.44 × 1010, and 1.72 × 109 M-1 s-1, respectively. Afterward, the coexisting bi/carbonate, acting as a shuttle, that promotes the transformation from HO• to RO• was evidenced to account for the better performance of the UV/PAA system in algae inactivation under the natural water background. Subsequently, along with the evaluation of the UV/PAA preoxidation to modify coagulation-sedimentation, the possible application of the UV/PAA process for algae removal was advanced.

A novel allogeneic acellular matrix scaffold for porcine cartilage regeneration.

BACKGROUND: Cartilage defects are common sports injuries without significant treatment. Articular cartilage with inferior regenerative potential resulted in the poor formation of hyaline cartilage in defects. Acellular matrix scaffolds provide a microenvironment and biochemical properties similar to those of native tissues and are widely used for tissue regeneration. Therefore, we aimed to design a novel acellular cartilage matrix scaffold (ACS) for cartilage regeneration and hyaline-like cartilage formation. METHODS: Four types of cartilage injury models, including full-thickness cartilage defects (6.5 and 8.5 mm in diameter and 2.5 mm in depth) and osteochondral defects (6.5 and 8.5 mm in diameter and 5 mm in depth), were constructed in the trochlear groove of the right femurs of pigs (n = 32, female, 25-40 kg). The pigs were divided into 8 groups (4 in each group) based on post-surgery treatment differences. was assessed by macroscopic appearance, magnetic resonance imaging (MRI), micro-computed tomography (micro-CT), and histologic and immunohistochemistry tests. RESULTS: At 6 months, the ACS-implanted group exhibited better defect filling and a greater number of chondrocyte-like cells in the defect area than the blank groups. MRI and micro-CT imaging evaluations revealed that ACS implantation was an effective treatment for cartilage regeneration. The immunohistochemistry results suggested that more hyaline-like cartilage was generated in the defects of the ACS-implanted group. CONCLUSIONS: ACS implantation promoted cartilage repair in full-thickness cartilage defects and osteochondral defects with increased hyaline-like cartilage formation at the 6-month follow-up.

A combined passivator of zeolite and calcium magnesium phosphate fertilizer: Passivation behavior and mechanism for Cd (II) in composting.

Passivation of heavy metals is one of the most efficient techniques to improve the quality of compost. Many studies confirmed the passivation effect of passivators (e.g., zeolite and calcium magnesium phosphate fertilizer) on cadmium (Cd), but passivators with single component could not effectively passivate Cd in the long-term operation of composting. In the present study, a combined passivator of zeolite and calcium magnesium phosphate fertilizer (ZCP) was used to explore its impacts of adding at different composting periods (heating period, thermophilic period, cooling period) on the Cd control, compost quality (e.g., temperature, moisture content and humification), microbial community structure as well as the compost available forms of Cd and addition strategy of ZCP. Results showed that Cd passivation rate could be increased by 35.70-47.92% under all treatments in comparison to the control treatment. By altering bacterial community structure, reducing Cd bioavailability and improving the chemical properties of the compost, the combined inorganic passivator could achieve high efficiency for Cd passivation. To sum up, the addition of ZCP at different composting periods has effects on the process and quality of composting, which could provide ideas for the optimization of the passivators addition strategy.

Non-Radical Activation of Peracetic Acid by Powdered Activated Carbon for the Degradation of Sulfamethoxazole.

Environmental-friendly and low-cost catalysts for peracetic acid (PAA) activation are vital to promote their application for micropollutant degradation in water. In this study, powdered activated carbon (PAC) was reported to improve the degradation of sulfamethoxazole (SMX). The improvement of SMX degradation in the PAC/PAA system was expected to be because of the PAA activation rather than the co-existing H2O2 activation. Non-radical oxidation pathways, including the mediated electron-transfer process and singlet oxygen (1O2), were evidenced to play the dominant roles in the degradation of micro-organic pollutants. The graphitization of PAC, persistent free radicals, and electron-donating groups like C-OH were proposed to contribute to the activation of PAA. High SMX degradation could be achieved in the acidic and neutral conditions in the PAC/PAA system. Overall, higher dosages of PAC (0-0.02 g/L) and PAA (0-100 µM) benefited the degradation of SMX. The presence of HCO3- could lower the SMX degradation significantly, while Cl-, PO43-, and humic acid (HA) only reduced the SMX degradation efficiency a little. Overall, this study offered an efficient non-radical PAA activation method using PAC, which can be effectively used to degrade micro-organic pollutants.

Cobalt-doped molybdenum disulfide for efficient sulfite activation to remove As(III): Preparation, efficacy, and mechanisms.

The sulfite(S(IV))-based advanced oxidation process has attracted significant attention in removing As(III) in the water matrix for its low-cost and environmental-friendly. In this study, a cobalt-doped molybdenum disulfide (Co-MoS2) nanocatalyst was first applied to activate S(IV) for As(III) oxidation. Some parameters including initial pH, S(IV) dosage, catalyst dosage, and dissolved oxygen were investigated. The experiment results show that >Co(II) and >Mo(VI) on the catalyst surface promptly activated S(IV) in the Co-MoS2/S(IV) system, and the electron transfer between Mo, S, and Co atoms accelerated the activation. SO4•- was identified as the main active species for As(III) oxidation. Furthermore, DFT calculations confirmed that Co doping improved the MoS2 catalytic capacity. This study has proven that the material has broad application prospects through reutilization test and actual water experiments. It also provides a new idea for developing bimetallic catalysts for S(IV) activation.

Comparison of peracetic acid and sodium hypochlorite enhanced Fe(â ¡) coagulation on algae-laden water treatment.

In this study, Fe(Ⅱ)/peracetic acid (PAA) and Fe(Ⅱ)/sodium hypochlorite (NaClO) systems were applied as the combined preoxidation and coagulation process to enhance algae removal. A high removal rate of algae and turbidity could be achieved, with most algal cells keeping intact when adding reasonable concentrations of PAA and NaClO to enhance Fe(Ⅱ) coagulation. The variations of chlorophyll a, malondialdehyde, and intracellular reactive oxygen species suggested that moderate oxidation with only destroying surface-adsorbed organic matter rather than cell integrity was realized. The generated organic radicals, Fe(Ⅳ), and hydroxy radical played the major roles in the Fe(Ⅱ)/PAA system for the moderate oxidation of algal cells, but direct oxidation by NaClO rather than producing reactive species in the Fe(Ⅱ)/NaClO process contributed to the preoxidation. Concurrently, the in-situ formed Fe(Ⅲ) greatly promoted the agglomerating and settling of algae. The analysis of cell integrity, biochemical compositions, and fluorescence excitation-emission matrices spectra demonstrated that excess NaClO but not PAA would seriously damage the algal cells. This might be because that NaClO would directly oxidize the cell wall/membrane, while PAA mainly permeates into the cell to inactivate algae. These results suggest that Fe(Ⅱ)/PAA is an efficient strategy for algae-laden water treatment without serious algae lysis.

New insights into the degradation of micro-pollutants in the hydroxylamine enhanced Fe(II)/peracetic acid process: Contribution of reactive species and effects of pH.

The hydroxylamine-enhanced Fe(II)/peracetic acid (PAA) process is a promising advanced oxidation process (AOP) with the generation of reactive species (RS) including RO•, •OH and Fe(IV). Nevertheless, it is still challenging to identify which RS is the major intermediate oxidant, and the reasons why the optimal condition is pH 4.5 rather than 3.0 are also unclear. Herein, the generation of RS and their contribution to the degradation of three micro-pollutants were explored. The quenching experiments and pseudo first-order kinetic model demonstrated that RO• rather than the other two RS were predominant. Then the overall generation and evolution pathways of RS were depicted. The elevation of pH (3.0-4.5) would accelerate the Fe(II)/Fe(III) redox cycle through the enhanced reduction of Fe(III) by hydroxylamine and induce the conversion of Fe(IV) to RO•, which benefited naproxen degradation. While the adverse Fe(III) precipitation would dominate the reduced degradation performance with the solution pH higher than 4.5. The elevation of PAA and Fe(II) dosages sped up the PAA activation, while excess hydroxylamine could consume the formed RS and exhibited an inhibitory effect. This study helps further understand the role of HA and differentiate the contribution of RS in the emerging PAA-based AOPs.

Blocking TRPV4 Ameliorates Osteoarthritis by Inhibiting M1 Macrophage Polarization via the ROS/NLRP3 Signaling Pathway.

Osteoarthritis (OA) is a low-level inflammatory disease in which synovial macrophage M1 polarization exacerbates the progression of synovitis and OA. Notedly, the ROS (reactive oxygen species) level in macrophages is intimately implicated in macrophage M1 polarization. TRPV4 (transient receptor potential channel subfamily V member 4), as an ion channel, plays a pivotal role in oxidative stress and inflammation. In this study, we investigated the role of TRPV4 in OA progression and M1 macrophage polarization. Male adult Sprague-Dawley (SD) rats underwent a medial meniscus radial transection operation to create an OA model in vivo and RAW 264.7 cells were intervened with 100 ng/mL LPS (lipopolysaccharide) to induce M1-polarized macrophages in vitro. We demonstrated that the infiltration of M1 synovial macrophages and the expression of TRPV4 were increased significantly in OA synovium. In addition, intra-articular injection of HC067074 (a specific inhibitor of TRPV4) alleviated the progression of rat OA and significantly decreased synovial macrophage M1 polarization. Further mechanisms suggested that ROS production by M1 macrophages was decreased after TRPV4 inhibition. In addition, NLRP3 (pyrin domain containing protein 3) as a downstream effector of ROS in M1-polarized macrophage, was significantly suppressed following TRPV4 inhibition. In conclusion, this study discovered that inhibition of TRPV4 delays OA progression by inhibiting M1 synovial macrophage polarization through the ROS/NLRP3 pathway.

Articular fibrocartilage-targeted therapy by microtubule stabilization.

The fibrocartilage presented on the joint surface was caused by cartilage injury or degeneration. There is still a lack of effective strategies for fibrocartilage. Here, we hypothesized that the fibrocartilage could be viewed as a raw material for the renewal of hyaline cartilage and proposed a previously unidentified strategy of cartilage regeneration, namely, "fibrocartilage hyalinization." Cytoskeleton remodeling plays a vital role in modifying the cellular phenotype. We identified that microtubule stabilization by docetaxel repressed cartilage fibrosis and increased the hyaline cartilage extracellular matrix. We further designed a fibrocartilage-targeted negatively charged thermosensitive hydrogel for the sustained delivery of docetaxel, which promoted fibrocartilage hyalinization in the cartilage defect model. Moreover, the mechanism of fibrocartilage hyalinization by microtubule stabilization was verified as the inhibition of Sparc (secreted protein acidic and rich in cysteine). Together, our study suggested that articular fibrocartilage-targeted therapy in situ was a promising strategy for hyaline cartilage repair.

[Interlaboratory comparison for determination of cadmium in drinking water].

OBJECTIVE: To analyze and evaluate the testing capability of cadmium in drinking water in the laboratories of the provincial and municipal centers for disease control and prevention across the country by implementing the interlaboratory comparison project. METHODS: The preparation method of the secondary standard materials were used as the reference for the sample preparation in the interlaboratory comparison project. The homogeneity and stability of the samples and short-term stability for simulated transportation were tested by single factor analysis of variance(ANOVA) and linear regression and mean consistency test(t test). On top of using the kernel density estimation to test the distribution of laboratory test result, we adopted precision statistical method to analyze the laboratory test result and used Z-score to evaluate the testing ability of each participating laboratory. RESULTS: A total of 409 laboratories throughout the country participated in the proficiency testing program.383 laboratories(93.6%) of participating laboratories, obtained satisfactory result. Results provided by 4 laboratories(1.0%) of total participating laboratories, were found suspicious in their capacities. Finally, there were 22 laboratories(5.4%) of total participating laboratories, with result found to be outliers. CONCLUSION: The statistical result of the interlaboratory comparison project show that the testing capability of cadmium in drinking water has been ranked as satisfactory in the laboratories of the provincial and municipal centers for disease control and prevention across the country, and the testing capability of a small number of laboratories requires further improvement.

[Interlaboratory comparison for determination of arsenic in drinking water].

OBJECTIVE: To analyze and evaluate the testing capability of arsenic in drinking water in the laboratories of the provincial and municipal centers for disease control and prevention across the country by implementing the interlaboratory comparison project. METHODS: The preparation method of the secondary standard materials were used as the reference for the sample preparation in the interlaboratory comparison project. The homogeneity and stability of the samples and short-term stability for simulated transportation were tested by single factor analysis of variance(ANOVA) and linear regression and mean consistency test(t test). On top of using the kernel density estimation to test the distribution of laboratory test result, we adopted precision statistical method to analyze the laboratory test result and used Z-score to evaluate the testing ability of each participating laboratory. RESULTS: A total of 411 laboratories throughout the country participated in the proficiency testing program.389 laboratories(94.6%) of participating laboratories, obtained satisfactory result. Results provided by 2 laboratories(0.5%) of total participating laboratories, were found suspicious in their capacities. Finally, there were 20 laboratories(4.9%) of total participating laboratories, with result found to be outliers. CONCLUSION: The testing capability of arsenic in drinking water has been ranked as satisfactory in the laboratories of the provincial and municipal centers for disease control and prevention across the country, and the testing capability of a small number of laboratories requires further improvement.

Single cell RNA-seq analysis identifies ferroptotic chondrocyte cluster and reveals TRPV1 as an anti-ferroptotic target in osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is the most common degenerative joint disease primarily characterized by cartilage destruction. The aim of this study was to investigate the role, molecular characteristics and potential therapeutic target of chondrocyte ferroptosis in the pathogenesis of OA. METHODS: The expression of ferroptotic hallmarks (iron and lipid peroxidation accumulation, glutathione deletion) were analyzed in paired intact and damaged cartilages from OA patients. Single cell RNA sequencing (scRNA-seq) analysis was performed on 17,638 chondrocytes to verify the presence, investigate the molecular signatures and unveil the potential therapeutic target of ferroptotic chondrocyte cluster in human OA cartilages. Destabilization of medial meniscus (DMM)-induced OA model and tert-butyl hydroperoxide (TBHP)-treated primary mouse chondrocytes and human cartilage explants were used to evaluate the protective effect of pharmacologically activated transient receptor potential vanilloid 1 (TRPV1). The downstream molecular mechanisms of TRPV1 was further investigated in glutathione peroxidase 4 (Gpx4) heterozygous genetic deletion mice (Gpx4+/-). FINDINGS: The concentrations of iron and lipid peroxidation and the expression of ferroptotic drivers in the damaged areas of human OA cartilages were significantly higher than those in the intact cartilage. scRNA-seq analysis revealed a chondrocyte cluster characterized by preferentially expressed ferroptotic hallmarks and genes, namely ferroptotic chondrocyte cluster. Comprehensive gene set variation analysis revealed TRPV1 as an anti-ferroptotic target in human OA cartilage. Pharmacological activation of TRPV1 significantly abrogated cartilage degeneration by protecting chondrocytes from ferroptosis. Mechanistically, TRPV1 promoted the expression of GPX4, and its anti-ferroptotic role was largely mitigated in the OA model of Gpx4+/- mice. INTERPRETATION: TRPV1 activation protects chondrocytes from ferroptosis and ameliorates OA progression by upregulating GPX4. FUNDING: National Key R&D Program of China (2018YFC1105904), Key Program of NSFC (81730067), National Science Foundation of China (81772335, 81941009, 81802196), Natural Science Foundation of Jiangsu Province, China (BK20180127), Jiangsu Provincial Key Medical Talent Foundation, Six Talent Peaks Project of Jiangsu Province (WSW-079).

Targeting macrophagic SHP2 for ameliorating osteoarthritis via TLR signaling.

Osteoarthritis (OA), in which M1 macrophage polarization in the synovium exacerbates disease progression, is a major cause of cartilage degeneration and functional disabilities. Therapeutic strategies of OA designed to interfere with the polarization of macrophages have rarely been reported. Here, we report that SHP099, as an allosteric inhibitor of src-homology 2-containing protein tyrosine phosphatase 2 (SHP2), attenuated osteoarthritis progression by inhibiting M1 macrophage polarization. We demonstrated that M1 macrophage polarization was accompanied by the overexpression of SHP2 in the synovial tissues of OA patients and OA model mice. Compared to wild-type (WT) mice, myeloid lineage conditional Shp2 knockout (cKO) mice showed decreased M1 macrophage polarization and attenuated severity of synovitis, an elevated expression of cartilage phenotype protein collagen II (COL2), and a decreased expression of cartilage degradation markers collagen X (COL10) and matrix metalloproteinase 3 (MMP3) in OA cartilage. Further mechanistic analysis showed thatSHP099 inhibited lipopolysaccharide (LPS)-induced Toll-like receptor (TLR) signaling mediated by nuclear factor kappa B (NF-κB) and PI3K-AKT signaling. Moreover, intra-articular injection of SHP099 also significantly attenuated OA progression, including joint synovitis and cartilage damage. These results indicated that allosteric inhibition of SHP2 might be a promising therapeutic strategy for the treatment of OA.

Identification of Transcription Factor Networks during Mouse Hindlimb Development.

Mammalian hindlimb development involves a variety of cells and the regulation of spatiotemporal molecular events, but regulatory networks of transcription factors contributing to hindlimb morphogenesis are not well understood. Here, we identified transcription factor networks during mouse hindlimb morphology establishment through transcriptome analysis. We used four stages of embryonic hindlimb transcription profiles acquired from the Gene Expression Omnibus database (GSE30138), including E10.5, E11.5, E12.5 and E13.5, to construct a gene network using Weighted Gene Co-expression Network Analysis (WGCNA), and defined seven stage-associated modules. After filtering 7625 hub genes, we further prioritized 555 transcription factors with AnimalTFDB3.0. Gene ontology enrichment showed that transcription factors of different modules were enriched in muscle tissue development, connective tissue development, embryonic organ development, skeletal system morphogenesis, pattern specification process and urogenital system development separately. Six regulatory networks were constructed with key transcription factors, which contribute to the development of different tissues. Knockdown of four transcription factors from regulatory networks, including Sox9, Twist1, Snai2 and Klf4, showed that the expression of limb-development-related genes was also inhibited, which indicated the crucial role of transcription factor networks in hindlimb development.

Photodegradation of chloramphenicol in micro-polluted water using a circulatory thin-layer inclined plate reactor.

This study describes the photodegradation of chloramphenicol (CAP) in micro-polluted water with a thin-layer inclined plate reactor. Under simulated sunlight irradiation, the effect of reaction parameters including solution pH, initial CAP concentration, and co-existed humic acid (HA) or chloride was evaluated. The photodegradation of CAP was independent of initial pH in the range of 6.0-9.0, but sharply decreased by 25.5% with the increase of initial CAP concentration from 0.4 to 1.0 mg/L. The presence of HA exhibited a significant inhibitory effect, while Cl- promoted the photoreaction. In this study, CAP was degraded through both direct and indirect photolysis, in which 1O2 was the main reactive species responsible for the indirect route. Its steady-state concentration in the micro-polluted water was determined to be 1.40 × 10-13 mol/L. Transformation intermediates were identified to propose the degradation pathway of CAP, which substantially met the density functional theory (DFT) calculation results. Moreover, four other pharmaceuticals including tetracycline, doxycycline, oxytetracycline, and minocycline were also successfully photodegraded during 5 h irradiation. Therefore, the designed circulatory thin-layer inclined plate reactor is suggested to be effectively applied to the decontamination of organic micro-polluted water.