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Abstract Background In the management of complex diseases, the strategic adoption of combination therapy has gained considerable prominence. Combination therapy not only holds the potential to enhance treatment efficacy but also to alleviate the side effects caused by excessive use of a single drug. Presently, the exploration of combination therapy encounters significant challenges due to the vast spectrum of potential drug combinations, necessitating the development of efficient screening strategies. Methods In this study, we propose a prediction scoring method that integrates heterogeneous data using a weighted Bayesian method for drug combination prediction. Heterogeneous data refers to different types of data related to drugs, such as chemical, pharmacological, and target profiles. By constructing a multiplex drug similarity network, we formulate new features for drug pairs and propose a novel Bayesian-based integration scheme with the introduction of weights to integrate information from various sources. This method yields support strength scores for drug combinations to assess their potential effectiveness. Results Upon comprehensive comparison with other methods, our method shows superior performance across multiple metrics, including the Area Under the Receiver Operating Characteristic Curve, accuracy, precision, and recall. Furthermore, literature validation shows that many top-ranked drug combinations based on the support strength score, such as goserelin and letrozole, have been experimentally or clinically validated for their effectiveness. Conclusions Our findings have significant clinical and practical implications. This new method enhances the performance of drug combination predictions, enabling effective pre-screening for trials and, thereby, benefiting clinical treatments. Future research should focus on developing new methods for application in various scenarios and for integrating diverse data sources.

Objective: The objective of this study is to investigate the heavy metal content in sediment and various organs of Hunan lotus seed in a planting area, as well as to explore the characteristics of heavy metal accumulation and transfer in Hunan lotus seed. Methods: A typical planting area in Hunan Province was selected for this research. The contents of Cd, Cr, Pb, Ni, Cu, Zn and Mn were measured using an inductively coupled plasma emission spectrometer. The bioconcentration factor （BCF） and transfer factor （TF） were used to evaluate the heavy metal accumulation and transfer ability of Hunan lotus seed. Results: The average content of Cd, Cr, Pb, Ni, Cu, Zn, and Mn in the sediment were 0.73, 176.28, 40.48, 27.61, 28.07, 95.57 and 311.68 mg/kg, respectively. Compared with the limit values of NY/T 391—2021, the exceeding rates of Cd, Cr, and Pb content are 100%, 75%, and 10%, respectively. The highest concentrations and contents of these 7 heavy metals were Cd, Cu and Zn in the lotus core, Cr and Pb in the root, Ni in the lotus-seed kernel and Mn in the leaves, with an average content of 0.20, 13.64, 78.58, 14.66, 2.23, 1.11 and 924.03 mg/kg, respectively. The BCFMn values for both stems and leaves exceeded 1. The TFCu values for all organs were greater than 1. Conclusion: This study reveals that there is serious pollution from Cd within the study area. The content of heavy metals in different organs of Hunan lotus seed is different. Lotus stems and leaves has strong enrichment of Mn, and Cu had strong transfer ability in Hunan lotus seed.

Abstract Elucidating the expression of microRNAs in developing single cells is critical for functional discovery. Here, we construct scCAMERA (single-cell cartography of microRNA expression based on reporter assay), utilizing promoter-driven fluorescent reporters in conjunction with imaging and lineage tracing. The cartography delineates the transcriptional activity of 54 conserved microRNAs in lineage-resolved single cells throughout C. elegans embryogenesis. The combinatorial expression of microRNAs partitions cells into fine clusters reflecting their function and anatomy. Notably, the expression of individual microRNAs exhibits high cell specificity and divergence among family members. Guided by cellular expression patterns, we identify developmental functions of specific microRNAs, including miR-1 in pharynx development and physiology, miR-232 in excretory canal morphogenesis by repressing NHR-25/NR5A, and a functional synergy between miR-232 and miR-234 in canal development, demonstrating the broad utility of scCAMERA. Furthermore, integrative analysis reveals that tissue-specific fate determinants activate microRNAs to repress protein production from leaky transcripts associated with alternative, especially neuronal, fates, thereby enhancing the fidelity of developmental fate differentiation. Collectively, our study offers rich opportunities for multidimensional expression-informed analysis of microRNA biology in metazoans.

Terahertz (THz) radiation is highly promising for various applications, from industrial inspections to medical diagnoses. Given the typically ultralow‐level power of generated THz radiation, the achievement of high responsivity in THz detection stands as a critical imperative for its applications. Graphene‐based detectors have become an attractive choice for THz detection due to the graphene unique 2D material structure, allowing a broad absorption spectrum and ultrafast response. Various plasmonic antenna arrays are also employed to couple with graphene, compensating for its modest optical absorption. However, the configuration of the plasmonic antenna arrays plays a crucial role in THz detection as it determines the graphene physical mechanisms of photodetection, directly impacting the final responsivity. Here, the key factors for achieving high responsivity are investigated and it is presented that reducing the gap size of the plasmonic antenna arrays to the nanoscale and implementing a series‐connection configuration can result in a remarkable increase in responsivity, often by several orders of magnitude. Importantly, this approach effectively prevents short circuits and minimizes dark current, further enhancing the overall performance of the detection system.

Asymmetric cell divisions (ACDs) generate two daughter cells with identical genetic information but distinct cell fates through epigenetic mechanisms. However, the process of partitioning different epigenetic information into daughter cells remains unclear. Here, we demonstrate that the nucleosome remodeling and deacetylase (NuRD) complex is asymmetrically segregated into the surviving daughter cell rather than the apoptotic one during ACDs in Caenorhabditis elegans. The absence of NuRD triggers apoptosis via the EGL-1-CED-9-CED-4-CED-3 pathway, while an ectopic gain of NuRD enables apoptotic daughter cells to survive. We identify the vacuolar H+–adenosine triphosphatase (V-ATPase) complex as a crucial regulator of NuRD’s asymmetric segregation. V-ATPase interacts with NuRD and is asymmetrically segregated into the surviving daughter cell. Inhibition of V-ATPase disrupts cytosolic pH asymmetry and NuRD asymmetry. We suggest that asymmetric segregation of V-ATPase may cause distinct acidification levels in the two daughter cells, enabling asymmetric epigenetic inheritance that specifies their respective life-versus-death fates.

Abstract Context With the development of society, the number of patients with osteoporosis is increasing. The prevention and control of osteoporosis has become a serious and urgent issue. With the continuous progress of biomedical research, ferroptosis has attracted increased attention. However, the pathophysiology and mechanisms of ferroptosis and osteoporosis still need further study. Natural products are widely used in East Asian countries for osteoporosis prevention and treatment. Objective In this paper, we will discuss the basic mechanisms of ferroptosis, the relationship between ferroptosis and osteoclasts and osteoblasts, and in vitro and in vivo studies of natural products to prevent osteoporosis by interfering with ferroptosis. Methods This article takes ferroptosis, natural products, osteoporosis, osteoblasts and osteoclast as key words. Retrieve literature from 2012 to 2023 indexed in databases such as PubMed Central, PubMed, Web of Science, Scopus and ISI. Results Ferroptosis has many regulatory mechanisms, including the system XC -/GSH/GPX4, p62/Keap1/Nrf2, FSP1/NAD (P) H/CoQ10, P53/SAT1/ALOX15 axes etc. Interestingly, we found that natural products, such as Artemisinin, Biochanin A and Quercetin, can play a role in treating osteoporosis by promoting ferroptosis of osteoclast and inhibiting ferroptosis of osteoblasts. Conclusions Natural products have great potential to regulate OBs and OCs by mediating ferroptosis to prevent and treat osteoporosis, and it is worthwhile to explore and discover more natural products that can prevent and treat osteoporosis.

This paper has proposed an improved single phase software phase lock loop (SPLL) with the ability of grid voltage DC and harmonics components suppression. An orthogonal signal generating method by frequency adaptive time delaying has been proposed to eliminate the grid voltage DC component, and frequency adaptive moving average filter (MAF) has been adopted to suppress the grid voltage harmonics. The loop transfer function has been deduced and the control parameter design of the MAF and SPLL controller has been detailed to balance between stability, overshoot and response time. Simulation experiments have shown that the proposed SPLL can correctly lock the fundamental frequency and phase even if there are large amounts of DC and high order harmonics components in the grid voltage.

Blau syndrome is a rare genetic disorder characterized by the a mix of granulomatous arthritis, uveitis, and dermatitis. Patients typically manifest multisystem involvement, including ocular, skin, and skeletal abnormalities. Blau syndrome is extremely rare, with a global incidence of less than one in a million among children. In this multidisciplinary consultation, we present a case of a 21-year-old young female patient having multisystemic involvement since early childhood. She was presented with multiple joint swelling, skin lesions, increased eye discharge, and accompanied by hypertension and arterial abnormalities, and received a diagnosis of uveitis. The patient had been receiving steroid treatment since the age of 6 and has tried various medications, with some improvement in joint swelling and ocular symptoms. Through this rare disease multidisciplinary consultation, we aim to provide guidance in the molecular diagnosis of the patient, multisystem assessment, and the selection and formulation of treatment plans. Additionally, we hope that by reporting this case, clinical physicians can gain a better understanding of the diagnosis and comprehensive treatment strategies for Blau syndrome, thereby improving the management and treatment of rare diseases.

Abstract Although various new biomaterials have enriched the methods for periodontal regeneration, their efficacy is still controversial, and the regeneration of damaged support tissue in the periodontium remains challenging. Laponite (LAP) nanosilicate is a layered two-dimensional nanoscale, ultrathin nanomaterial with a unique structure and brilliant biocompatibility and bioactivity. This study aimed to investigate the effects of nanosilicate-incorporated PCL (PCL/LAP) nanofibrous membranes on periodontal ligament cells (PDLCs) in vitro and periodontal regeneration in vivo. A PCL/LAP nanofibrous membrane was fabricated by an electrospinning method. The characterization of PCL/LAP nanofibrous membrane were determined by scanning electron microscopy (SEM), energy dispersive spectrum of X-ray (EDS), inductively coupled plasma mass spectrometry (ICP-MS) and tensile test. The proliferation and osteogenic differentiation of PDLCs on the PCL/LAP nanofibrous membrane were evaluated. A PDLCs and macrophage coculture system was used to explore the immunomodulatory effects of the PCL/LAP nanofibrous membrane. PCL/LAP nanofibrous membrane was implanted into rat calvarial and periodontal defects, and the regenerative potential was evaluated by microcomputed topography (micro-CT) and histological analysis. The PCL/LAP nanofibrous membrane showed good biocompatibility and bioactivity. It enhanced the proliferation and osteogenic differentiation of PDLCs. The PCL/LAP nanofibrous membrane also stimulated anti-inflammatory and pro-remodeling N2 neutrophil formation, regulated inflammatory responses and induced M2 macrophage polarization by orchestrating the immunomodulatory effects of PDLCs. The PCL/LAP nanofibrous membrane promoted rat calvarial defect repair and periodontal regeneration in vivo. LAP nanosilicate-incorporated PCL membrane is capable of mediating osteogenesis and immunomodulation of PDLCs in vitro and accelerating periodontal regeneration in vivo. It could be a promising biomaterial for periodontal regeneration therapy.

Using the final state analysis method (fracture morphology analysis), it is difficult to establish the dynamic changes that would have occurred during the process of necking under tensile load. In this paper, the time-dependent observations, the critical hole expansion ratio model and the Bridgeman equation is applied to establish the relationship between the dynamics of necking and the microscopic parameters that describe fracture in samples made from the low-carbon steel. The results show that the axial (x) and radial (y) displacements observed in the necking process are described by the Gaussian function. And the curve of the neck contraction (yc) and time (t) indicates that the macroscopic deformation process behind necking can be divided into three stages, which correspond to microcrack propagation in the fiber area, the radiation area, and the shear lip area. Following, by considering the fitted model of x-y, the critical hole expansion ratio model and the Bridgeman equation, a novel model between the macroscopic deformation (parameters of yc and εt) observed in necking and the formation of micropores (parameter of Rc) is established, which can disclose the effect of macroscopic deformation on the formation of the micro-voids, and plays a role in the study of plastic deformation mechanisms in a wide range of materials.

Objectives: To analyze and describe the spatiotemporal trends of Low back pain (LBP) burdens from 1990 to 2019 and anticipate the following decade’s incidence.Methods: Using data from the Global Burden of Disease (GBD) 2019 Study, we described net drifts, local drifts, age effects, and period cohort effects in incidence and forecasted incidence rates and cases by sex from 2020 to 2029 using the Nordpred R package.Results: LBP remained the leading cause of the musculoskeletal disease burden globally and across all socio-demographic index (SDI) regions. China is the top country. For recent periods, high-SDI countries faced unfavorable or worsening risks. The relative risk of incidence showed improving trends over time and in successively younger birth cohorts amongst low-middle-, middle- and high-middle-SDI countries. Additionally, the age-standardized incidence rates (ASIR) of LBP in both sexes globally showed a decreasing trend, but the incident cases would increase from 223 to 253 million overall in the next decade.Conclusion: As the population ages, incident cases will rise but ASIR will fall. To minimise LBP, public awareness and disease prevention and control are needed.

Osteoporosis is the result of osteoclast formation exceeding osteoblast production, and current osteoporosis treatments targeting excessive osteoclast bone resorption have serious adverse effects. There is a need to fully understand the mechanisms of osteoclast-mediated bone resorption, identify new drug targets, and find better drugs to treat osteoporosis. Gar C (Gar C) is a major naturally occurring phytochemical isolated from mangosteen, and is a derivative of the naturally occurring phenolic antioxidant lutein. We used an OP mouse model established by ovariectomy (OVX). We found that treatment with Gar C significantly increased bone mineral density and significantly decreased the expression of TRAP, NFATC1 and CTSK relative to untreated OP mice. We found that Garcinone C could disrupt osteoclast activation and resorption functions by inhibiting RANKL-induced osteoclast differentiation as well as inhibiting the formation of multinucleated osteoclasts. Immunoblotting showed that Gar C downregulated the expression of osteoclast-related proteins. In addition, Gar C significantly inhibited RANKL-induced ROS production and affected NF-κB activity by inhibiting phosphorylation Formylation of P65 and phosphorylation and degradation of ikba. These data suggest that Gar C significantly reduced OVX-induced osteoporosis by inhibiting osteoclastogenesis and oxidative stress in bone tissue. Mechanistically, this effect was associated with inhibition of the ROS-mediated NF-κB pathway.

Lunar igneous activities, including intrusive magmatism and extrusive volcanism, and their products contain significant information about the lunar interior and its thermal state. Their distribution is asymmetrical on the nearside and farside, reflecting the global dichotomy. Samples from the South Pole–Aitken (SPA) basin on the farside hold the key to disclosing the dichotomy conundrum and rebalancing the asymmetrical understandings of the Moon, in addition to previously returned nearside samples (Apollo, Luna, Chang’e-5). For the first time, the Chang’e-6 mission obtained ∼1935.5 g of lunar soils from the farside in the southern Apollo basin, northeast of SPA, opening a window to solve this long-standing question. However, compared with the well-known mare/cryptomare volcanism in SPA, intrusive activity has a much more obscure presence and origin, due to its unclear surface expression, thus impeding the ongoing Chang’e-6 sample analysis, which is therefore emphasized here. We found evidence that intrusive magmatism is extensive across SPA, including Mg-suite intrusions, floor-modified craters, and linear/ring dikes, consistent with its intermediate crustal thickness, where dike intrusion is favored. Intrusive magmatism is abundant in the Apollo basin, where Chang’e-6 landed. Two obscure craters were discovered (Apollo X and Q) with evidence for subsurface intrusions, strongly suggesting the intensive intrusion in the region. Plutonic materials are very likely to be obtained by Chang’e-6, especially the Mg-suite from the western peak ring of the Apollo basin that delivered and mixed in the soils by the Chaffee S crater, whose components might provide critical new insights into their petrogenesis, early lunar evolution, and the origin of dichotomy.

Abstract Developing a living prosthetic breast to inhibit potential breast cancer recurrence and simultaneously promote breast reconstruction would be a promising strategy for clinical treatment of breast cancer after mastectomy. Here, a living prosthetic breast in the form of injectable gelatin methacryloyl microspheres is prepared, where they encapsulated zeolitic imidazolate framework (ZIF) nanoparticles loaded with small molecules urolithin C (Uro‐C) and adipose‐derived stem cells (ADSCs). Taking advantage of the acidic tumor microenvironment, the ZIF triggered a pH‐sensitive drug release in situ so that Uro‐C can induce tumor cell apoptosis via reactive oxygen species (ROS) generation. Meanwhile, the ADSCs proliferate in situ to promote tissue regeneration. Using such a design, our data showed that the ADSCs maintained viable and proliferate under the inhibitory effect of Uro‐C in vitro. Through ROS generation, Uro‐C also activated a suppressive tumor microenvironment in mice by both re‐polarizing M2 macrophages to M1 macrophages for elevated inflammatory responses, and increasing the ratio between CD8 and CD4 T cells for tumor recurrence inhibition, significantly promoting new adipose tissue formation. Altogether, our results demonstrate that the prepared living prosthetic breast with bifunctional properties can be a promising candidate in clinic involving tumor treatment and tissue engineering in synergy.

This paper focuses on introducing a modular cascaded battery energy storage system and establishing a mathematical model for both the AC and DC sides of the energy storage system. Based on this, a corresponding control strategy is proposed. To achieve a specific trade-off between switching times and output harmonics, a new hybrid modulation strategy (NHPWM) is proposed that combines the characteristics of NLM and CPS-PWM commonly used in traditional modular cascaded topologies. With this hybrid modulation strategy, the modulation of each sub-module can be flexibly configured, allowing the system to coordinate device loss and output harmonic characteristics in real time according to system requirements. Additionally, this paper proposes a calculation method based on the theory of double Fourier series expansion to derive the analytical solution of the NHPWM harmonic distribution, providing a theoretical basis for sub-module modulation mode configuration. Finally, the correctness and effectiveness of the modulation strategy and theoretical calculation were verified by simulation and experiment. The proposed method in this paper has demonstrated clear advantages over traditional HPWM and CPS-PWM in terms of harmonics and efficiency, as shown by the experimental results.

The application of pulse width modulation (PWM) technology will produce a high-frequency switching ripple. Generally, it is considered to filter it with an LCL filter to ensure the compensation performance of the shunt active power filter. According to the system requirements for ripple current suppression and maximum current tracking capability, this paper first optimizes the design of the filter inductance in the LCL. Then, aiming at the shortcomings of the traditional inductor design process that is complicated and cumbersome, with repetitiveness and difficulty to obtain reliable analytical solutions, a 4-dimensional visualization based multi-objective optimized algorithm is proposed, and the ternary function expression between each design goal and known independent variables is first derived and established. And then, through the visual programming of the 4-dimensional data field, the optimal solution set that meets the multi-objective design requirements is directly given, which is intuitive, clear, simple, and practical. Finally, according to the algorithm results, the corresponding inductance was wound and applied to a 50kVA three-phase four-wire active power filter prototype. The experimental results verified the feasibility and effectiveness of the proposed design method.

Helicteres angustifolia L. (Helicteres angustifolia) has been commonly used in folk medicine to treat cancer; however, its mechanisms of action remain obscure. In our earlier work, we reported that aqueous extract of H. angustifolia root (AQHAR) possesses attractive anticancer properties. In the present study, we isolated five ethanol fractions from AQHAR and investigated their therapeutic efficacy in human non-small cell lung cancer (NSCLC) cells. The results showed that among the five fractions, the 40% ethanol fraction (EF40) containing multiple bioactive compounds exhibited the best selective killing effect on NSCLC cells with no obvious toxicity to normal human fibroblasts. Mechanistically, EF40 reduced the expression of nuclear factor-E2-related factor 2 (Nrf2), which is constitutively expressed at high levels in many types of cancers. As a result, Nrf2-dependent cellular defense responses are suppressed, leading to the intracellular accumulation of reactive oxygen species (ROS). Extensive biochemical analyses revealed that EF40 caused cell cycle arrest and apoptosis through activation of the ROS-mediated DNA damage response. Furthermore, treatment with EF40 compromised NSCLC cell migration, as evidenced by the downregulation of matrix metalloproteinases (MMPs) and heterogeneous nuclear ribonucleoprotein K (hnRNP-K). In vivo studies using A549 xenografts in nude mice also revealed significant suppression of tumor growth and lung metastasis in the treated group. We propose that EF40 may serve as a potential natural anti-NSCLC drug that warrants further mechanistic and clinical attention.

Electrocatalytic reduction of CO2 into multi-carbon alcohols of high economic merit offers an effective means to close the carbon cycle. Here the authors show the synergy between inorganic and organic phases derived from rationally designed molecular precursors to produce alcohols in high efficiency.

From the perspective of complex vector, this paper derives the mathematical model of the three-phase three-wire shunt active power filter (SAPF) current control object, and based on it, derives the corresponding vector resonance control expression form coordinate transformation, and the steady-state accuracy, anti-interference ability, and stability of the system are analyzed. The deduction demonstrates the equivalence of the traditional detection load harmonic current control and the direct grid current control in this paper, and the consistency of the current regulator. Then, a direct vector resonance control structure of grid current based on the dq coordinate without detecting harmonic currents is designed, and the digital realization of the vector resonance controller, the adaptive ability to frequency, and the phase lag at the high-order control frequency are designed. And finally experimental verification under different working conditions is presented, the experimental results prove the practicability and effectiveness of the direct current control strategy based on the vector resonance controller proposed in this paper.

Aiming at the heat dissipation design problem of shunt active power filter, this paper proposes a computational fluid dynamics (CFD) simulation method of module flow–heat transfer coupling under forced air cooling. The power filter has carried out a detailed heat generation analysis, and given the analysis and simulation results, the heat dissipation system of the parallel active power filter is designed. The experimental results of the compensation performance prove that the designed modular system has an excellent dynamic, steady-state performance, and temperature rise. The experimental results are consistent with the simulation analysis, which demonstrates the effectiveness of the heat dissipation design of the parallel active power filter module proposed in this paper.

Analyze the electromagnetic interference (EMI) of the primary circuit of the switch tube driving power in the three-phase half-bridge converter, and study how to improve the electromagnetic compatibility (EMC) performance. The high-frequency EMI source caused by high-speed switching in the three-phase half-bridge converter is analyzed and quantitatively calculated. The high-frequency conduction model of the three-phase half-bridge converter and the driving power supply is established. Through the establishment of a high-frequency model, it is pointed out that EMI sources cause three interference conduction paths to the driving power supply: conduction paths I and II between the primary circuit and the driving power supply, conduction paths III between the driving power supply, and use the high-frequency model to obtain three conduction paths Based on the equivalent high-frequency circuit of the channel and the corresponding transfer function, a general method for suppressing three kinds of interference and improving the EMC performance of the drive power is proposed based on the transfer function. The experimental results show that the interference between the driving power supplies is the direct interference. The interference can be significantly reduced by paralleling the capacitors in the ambitious power load.

Objective: To investigate the effect and clinical significance of myeloid-derived suppressor cells (MDSCs) levels and serum miRNA-21 expression in advanced non-small cell lung cancer (NSCLC) patients. Methods: Advanced NSCLC patients treated at the First People’s Hospital of Tongxiang City, Zhejiang Province, between July 2021 and June 2022 were included in this study. MDSCs in the peripheral circulation were assessed by flow cytometry, and serum miRNA-21 expression was assessed by q-PCR. The effects of miRNA-21 on MDSC proliferation and ARG-1 and inducible nitric oxide synthase (iNOS) secretion from MDSCs were examined using in vitro cell experiments. In addition, the correlation between MDSC and CEA, CRP and Ki67 was analyzed. Results: Compared with those in the peripheral circulation of individuals in the control group, the expression levels of polymorphonuclear-MDSCs (PMN-MDSCs) and miRNA-21 in the peripheral circulation of NSCLC patients were significantly higher, and the two groups were significantly positively correlated. In in vitro cell experiments, miRNA-21 mimics promoted MDSC proliferation and increased ARG-1 and iNOS secretion and miRNA-21 inhibtor has an opposite result. In addition, PMN-MDSCs in the peripheral circulation of NSCLC patients were significantly positively correlated with carcinoembryonic antigen (CEA), C-reactive protein (CRP), and Ki67. Conclusion: The blood of advanced NSCLC patients contains high levels of MDSCs and miRNA-21, and the two may interact to impact on NSCLC.

Abnormal bone metabolism and subsequence osteoporotic fractures are common complications of chronic inflammatory diseases. No effective treatment for these bone-related complications is available at present. The chronic inflammatory state in these diseases has been considered as a key factor of bone loss. Therefore, the combination of inflammation inhibition and bone loss suppression may be an important strategy for reducing bone damage associated with inflammatory diseases. Bushen Huoxue Decoction (BSHXD) is a traditional Chinese herbal compound that has demonstrated the ability to improve bone quality and increase bone density. However, the efficacy of BSHXD on inflammatory bone loss and its underlying mechanisms remain unclear. This study aimed to investigate whether BSHXD inhibits inflammatory bone loss in mice and its potential molecular mechanisms. In the present study, the effect of BSHXD on lipopolysaccharide (LPS)-induced M1 polarization of RAW264.7 macrophage and on local inflammatory bone loss model of mouse skull was determined. The results showed that after treating RAW264.7 cells with LPS for 24 h, the expression levels of IL-1β (39.42 ± 3.076 ng/L, p

Abstract Aqueous activities on Mars have gradually declined since the Noachian (>3.7 Ga). Although water can be stored in the subsurface during the latest epochs, geomorphological evidence is still limited. In this study, we used in situ imaging and spectral data acquired by China's Zhurong rover, as well as high‐resolution remote‐sensing data, to investigate the transverse aeolian ridges (TARs) in the Zhurong landing region of Utopia Planitia. A two‐stage evolutionary scenario of the TARs is proposed and polygonal features with hydrated minerals are identified for the first time on the surface of Martian TARs. We discussed the possible formation mechanisms of the polygonal features, and proposed that they could be related to recent aqueous activity and atmosphere‐surface water exchange on Mars, which sheds light on the hydrological cycle of Mars in current cold and dry climate.

An intelligent temperature measurement solution based on “5G+AI” for the prevention and control of epidemic situation in COVID-19 was presented.Intelligent temperature measurement has a wide range of application scenarios in areas with dense traffic such as airports, railway stations and stations.A new AI temperature measurement architecture was proposed.The camera and infrared thermometer was used to measure temperature.The preprocessing module included image decoding, color space transformation, image correction and image normalization.Head detection model need to undergo off-line model training.Finally, through the temperature calculation module, the structured information was output.The development process of the model included data collection and annotation, model construction, model training, model optimization and model deployment.A comprehensive intelligent temperature measurement system was constructed, which integrated 5G temperature measurement hardware, OneNET access platform, monitoring application platform and mobile App.Finally, “5G+AI” intelligent temperature measurement products were successfully deployed in many cities and different application scenarios across the country.

Mesenchymal stem cells(MSCs) are adult stem cells that possess the ability of self-renewal and multi-lineage differentiation. They can be found in multiple tissue types, including adipose tissue, bone marrow and umbilical cord. MSCs can exert the effects of tissue repair, angiogenesis, immunoregulation, and anti-fibrosis through differentiation or paracrine function. Promising therapeutic effects of MSCs on skin aging, alopecia, tissue regeneration, wound healing, and anti-fibrosis have been observed. In general, MSCs exhibit favorable therapeutic effects and safety, but scrutinized research and clinical trials are still needed to reveal the mechanism of action as well as long-term efficacy and safety.

Aesthetic medicine includes aesthetic surgery, cosmetic dermatology, aesthetic dentistry and aesthetic Chinese medicine. The goal of aesthetic medicine is to maintain, modify and remodel the beauty of appearance through medical methods. The shaping of beauty mainly relies on aesthetic surgery, which is the principal part of aesthetic medicine. With the increasing demand for beauty, the medical aesthetic industry has flourished in recent decades, and the complications of aesthetic surgery also have been rising. This article summarizes the complications related to aesthetic medicine in order to provide a warning for clinical diagnosis and treatment.

Localized scleroderma is a rare auto-immune disorder characterized by inflammation and fibrosis of the skin and subcutaneous fat in the affected area, leaving aesthetic impairment to the patients.Such patients often seek plastic surgery for the treatment. This article summarizes the pathophysiology and preoperative evaluation of localized scleroderma, discusses the progress and clinical dilemma of its surgical treatment, and shares the opinions on the diagnosis and treatment of a single center in Peking Union Medical College Hospital.

Objective To design a safety management system for antitumor drugs, which can intercept or warn the overdose of medical orders from the prescription source, and ensure the safety of clinical application of antitumor drugs. Methods The threshold of interception and warning strategy of 88 kinds of antitumor drugs were developed, and the safety management system of antitumor drugs was established to intercept or warn the overdose orders. The interception and warning data from January 2021 to June 2021 in the safety management system of antitumor drugs were extracted and analyzed. Results A total of 665 medical orders were intercepted or warned by the safety management system of antitumor drugs, and the majority of the intercepted or warned drugs were oral tablets(74.29%). The intercepted orders were 642 (96.54%), and the warned orders were 23(3.46%). Among the intercepted medical orders, frequency error (64.22%) has the highest proportion, followed by route error (11.73%) and dose error (9.92%). A total of 564 medical orders were intercepted, involving 28 kinds of antitumor drugs. Methotrexate tablets ranked first in overdose quantity, with an average of seven times. Pemetrexed ranked first in overdose multiples, with an average overdose of 1000 times. 78 medical orders were intercepted for over pathway, involving 5 kinds of antitumor drugs. Conclusion The safety management system of antitumor drugs can eliminate the error of overdose in prescription and guarantee the safety of antitumor drugs.

Widely applied in medical, industrial, and military fields, the high-voltage power supply based on LCC resonant converter (LCC) is ought to establish tens kilovolts of output voltage within milliseconds according to many standards. And any overshoot during this start-up process is not allowed because of the issue or even deadly consequence it may lead. Traditional linear control schemes are powerless to fulfill these two conflicting requirements, especially for the LCC with nonlinear gain characteristics. In this paper, a multi-segment fuzzy control is proposed to tackle this problem. Firstly, the nonlinear gain curve of LCC is piecewise linearized based on its large-signal model, and the control requirements for different segments are determined. Then the control parameters for each part are selected by an off-line fuzzy algorithm. The allowed minimum frequency during the start-up is also piecewise linearized so that the gain ability of LCC is utilized. Finally, the proposed control scheme is verified with an 80kW/150kV X-ray power supply. A low-cost controller is used to implement the start-up control scheme since the control parameters can be pre-calculated and stored in the controller. Compared with the commonly used linear PI control, the non-overshoot start-up time with the proposed control scheme is reduced by more than 60%.

Lymphedema is a hot issue that has attracted wide attention in the field of rehabilitation medicine in recent years. The complex decongestive therapy of lymphedema including manual lymphatic drainage(MLD) as the key technology is developing rapidly all over the country.We report a rare case of aggravated primary lymphedema in the contralateral limb and trunk after radical mastectomy. The patient achieved remission through MLD treatment. By reviewing the diagnosis and treatment of this case, we can deepen the understanding of the complexity of the pathogenesis of lymphedema and provide reference for individualized diagnosis and treatment of lymphedema.

Abstract Background The inhibition of osteogenic differentiation is a major factor in glucocorticoid-induced bone loss, but there is currently no effective treatment. Dopamine, a major neurotransmitter, transmits signals via five different seven-transmembrane G protein-coupled receptors termed D1 to D5. Although the relevance of the neuroendocrine system in bone metabolism has emerged, the precise effects of dopamine receptor signaling on osteoblastogenesis remain unknown. Methods In vitro, western blotting and immunofluorescence staining were used to observe the expression of dopamine receptors in MC3T3-E1 and BMSCs cells treated with dexamethasone (Dex). In addition, Alizarin red S (ARS) and alkaline phosphatase (ALP) staining and western blotting were used to evaluate the effect of D1R activation on osteogenic differentiation in Dex-induced MC3T3-E1 cells via the ERK1/2 signaling pathway. In vivo, micro-CT and hematoxylin and eosin (H&E), toluidine blue and immunohistochemical staining were used to determine the effect of D1R activation on Dex-induced bone loss. Results We demonstrated that the trend in D1R but not D2-5R was consistent with that of osteogenic markers in the presence of Dex. We also demonstrated that the activation of D1R promoted Dex-induced osteogenic differentiation by activating the ERK1/2 pathway in vitro. We further demonstrated that a D1R agonist could reduce Dex-induced bone loss, while pretreatment with a D1R inhibitor blocked the effect of a D1R agonist in vivo. Conclusions Activation of D1R promotes osteogenic differentiation and reduces Dex-induced bone loss by activating the ERK1/2 pathway. Hence, D1R could serve as a potential therapeutic target for glucocorticoid-induced osteoporosis.

Currently, the failure rate for internal fixation in patients with osteoporosis can be reduced by antiosteoporosis therapy alone. However, the administration of anti-osteoporotic drugs is not a complete solution. Therefore, it is necessary to investigate other causes of surgical failure, such as inflammation. In recent years, the inflammation caused by macrophage M1 polarization has garnered wide attention. The purpose of this research is to explore the inhibitory effect of avicularin (AL) on macrophage M1 polarization, by which it ameliorates inflammation, thus alleviating implant instability. We established an osteoporosis mouse model of implant loosening. The mouse tissues were taken out for morphological analysis, staining analysis and bone metabolic index analysis. In in vitro experiments, bone marrow derived macrophages (BMDM) and RAW264.7 cells were polarized to M1 macrophages using lipopolysaccharide (LPS), and analyzed by immunofluorescence (IF) staining, Western blot (WB) and flow cytometry. WB was also used to analyze the nuclear factor kappa-B (NF-κB) pathway. In addition, the expression levels of inflammatory cytokines were detected in cell supernatant using ELISA kits. Through observation of this experiments, we found that AL can inhibit M1 polarization of macrophages. Moreover, it can significantly inhibit the release of inflammatory factors to improve multiple mouse femur parameters. Furthermore, AL inhibited the phosphorylation of IKBα and P65 in the NF-κB pathway. The above data indicate that AL ameliorates inflammatory responses by inhibiting macrophage M1 polarization via its inhibitory effect on the NF-κB pathway, thus alleviating the instability of implants in mice with osteoporosis.

Volcanism is the most important endogenic geological process of the Moon, which is closely related to its internal structure and thermal history. Lunar volcanism is one of the most important topics for lunar science and explorations. Recent lunar orbital observations, in situ explorations, and sample return missions have returned a new generation of high-resolution datasets, which greatly enriched our knowledge of lunar volcanism. Here, we summarize recent advances in the duration and spatial distribution of lunar mare volcanism, as well as origin of volcanic landforms such as lava flows, sinuous rilles, lava tubes, domes, and cones. We proposed several outstanding problems in the study of temporal and spatial span of lunar volcanism, the formation mechanism of the varied volcanic landforms, and their relation with deep structures. To solve these problems, more in situ explorations and sample return missions from various volcanic units are needed.

Periprosthetic osteolysis (PPO), caused by wear particles, has become a major cause of joint replacement failure. Secondary surgery after joint replacement poses a serious threat to public health worldwide. Therefore, determining how to effectively inhibit wear particle-induced PPO has become an urgent issue. Recently, the interaction between osteogenic inhibition and wear particles at the biological interface of the implant has been found to be an important factor in the pathological process. Previous studies have found that the central nervous system plays an important role in the regulation of bone formation and bone remodeling. Dopamine (DA), an important catecholamine neurotransmitter, plays an integral role in the physiological and pathological processes of various tissues through its corresponding receptors. Our current study found that upregulation of dopamine first receptors could be achieved by activating the Wnt/β-catenin pathway, improving osteogenesis in vivo and in vitro, and significantly reducing the inhibition of titanium particle-induced osteogenesis. Overall, these findings suggest that dopamine first receptor (D1R) may be a plausible target to promote osteoblast function and resist wear particle-induced PPO.

Background: Osteoarthritis is a common chronic degenerative disease, and recently, an increasing number of studies have shown that immunity plays an important role in the progression of osteoarthritis, which is exacerbated by local inflammation. The role of N6-methyladenine (m6A) modification in immunity is being explored. However, the role of m6A modification in regulating the immune microenvironment of osteoarthritis remains unknown. In this study, we sought to discuss the association between the N6-methyladenine (m6A) modification and the immune microenvironment of osteoarthritis.Methods: First, the data and gene expression profiles of 139 samples, including 33 healthy samples and 106 osteoarthritis samples, were obtained from the Genetics osteoARthritis and Progression (GARP) study. Then the differences in m6A regulators between healthy individuals and osteoarthritis patients were analyzed. The correlation between m6A regulators and immune characteristics was also investigated by single-sample gene set enrichment analysis (ssGSEA). Principal component analysis (PCA), Gene Set Variation Analysis (GSVA) enrichment analysis, weighted gene coexpression network analysis (WGCNA), and Associated R packages were used to identify the m6A phenotype and its biological functions.Results: A total of 23 m6A regulators were involved in this study. We found a close correlation between most m6A regulators in all samples as well as in osteoarthritis samples. VIRMA and LRPPRC were the most highly correlated m6A regulators and showed a positive correlation, whereas VIRMA and RBM15B were the most negatively correlated. M6A regulators are associated with osteoarthritis immune characteristics. For example, MDSC cell abundance was strongly correlated with RBM15B and HNRNPC. Meanwhile, RBM15B and HNRNPC were important effectors of natural killer cell immune responses. IGFBP3 is an important regulator of cytolytic activity immune function. We performed an unsupervised consensus cluster analysis of the osteoarthritis samples based on the expression of 23 m6A regulators. Three different m6A subtypes of osteoarthritis were identified, including 27 samples in subtype C1, 21 samples in subtype C2, and 58 samples in subtype C3. Different m6A subtypes have unique biological pathways and play different roles in the immune microenvironment of osteoarthritis.Conclusion: The m6A modification plays a crucial role in the diversity and complexity of the immune microenvironment in osteoarthritis.

Molecular imaging plays an increasingly important role in the early diagnosis and detection of tumors. As a significant branch of molecular imaging, magnetic resonance imaging (MRI) shows incomparable advantages and broad development prospects than other imaging technologies. It requires no radioactive tracer, no ionizing radiation, but presents high spatial and temporal resolution and tissue contrast. In recent years, a series of progress has been made in the research and development of new magnetic resonance molecular probes and imaging sequences, including responsive molecular probes, 19F MRI, hyperpolarized 129Xe MRI, and chemical exchange saturation transfer (CEST) imaging, which have expanded the application range of MRI. One crucial research in MRI development is to further improve sensitivity. Therefore, the research of new multimodal MRI contrast agents with good targeting capacity, high relaxation efficiency and high safety is an important topic in the current biomedical engineering field. For example, the sensitivity of MRI molecular probes could be improved by combining the characteristics of micelles with some new magnetic resonance methods. Some deficiencies of MRI could be overcome by introducing multimodal molecular probes. This article reviews the research progress and application analysis of the core technology of micellar MRI molecular probes, and elucidates the importance of molecular imaging technology in biomedical engineering research and clinical diagnosis.

Wound healing, a highly complex pathophysiological response to injury, includes four overlapping phases of hemostasis, inflammation, proliferation, and remodeling. Initiation and resolution of the inflammatory response are the primary requirements for wound healing, and are also key events that determines wound quality and healing time. Currently, the number of patients with persistent chronic wounds has generally increased, which imposes health and economic burden on patients and society. Recent studies have found that microRNA(miRNA) plays an essential role in the inflammation involved in wound healing and may provide a new therapeutic direction for wound treatment. Therefore, this review focused on the role and significance of miRNA in the inflammation phase of wound healing.

Hyperprolactinemia is a common endocrine disease in women of reproductive age. Research has shown that patients with hyperprolactinemia often have decreased bone mineral density and an increased risk of fractures. However, there is still a lack of effective treatments. Paeoniflorin, one of the primary bioactive components in peony, is widely used in traditional Chinese medicine. Research has shown that paeoniflorin promotes osteoblast differentiation. However, whether paeoniflorin plays a role in hyperprolactinemia-induced osteoblastogenesis inhibition is not yet clear. In this study, we investigated the effect of paeoniflorin on prolactin (PRL)-mediated inhibition of osteoblast function. Our results showed that prolactin significantly reduced the expression of alkaline phosphatase (ALP), Osterix, and runt-related transcription factor 2 (RUNX2) in MC3T3-E1 cells cultured in an osteoblast differentiation medium, suggesting that prolactin inhibited osteoblast function. After treatment with paeoniflorin (PF), the expression of these osteoblast markers was upregulated. In addition, our findings proved that paeoniflorin increased the absorbance values of ALP-positive cells and the areas of alizarin red S (ARS) deposition compared to those in the prolactin group, suggesting that paeoniflorin reversed the PRL-induced reduction in osteoblast differentiation. The PRL-induced activation of nuclear factor kappa B (NF-κB) was significantly reversed by paeoniflorin, indicating that paeoniflorin promoted osteoblast function by inhibiting the NF-κB signaling pathway. In summary, these results showed that paeoniflorin alleviated the inhibitory effect of prolactin on osteoblastogenesis by suppressing the NF-κB signaling pathway.

As one of the major ice reservoirs on Mars, the south polar layered deposits (SPLD) are mainly composed of water ice and dust except for the perennial CO _2 ice deposits on the surface and within buried layers. At the edge of Planum Australe, the Shallow Radar detected the base of two ice lobes, which can be used to estimate their dielectric properties and analyze the components. These measurements, combined with topographic data, allow for the relative permittivity of the lobe materials to be estimated at 2.73 ± 0.67. Under the constraint of the SPLD density, the permittivity value translates to the existence of CO _2 ice depending on the dust content. If the dust content is larger than 24%, the lobes are CO _2 free and composed of water ice, dust, and pore space. Whereas, for the dust content of

Ongoing efforts have been made to improve the photoresponsivity of plasmonic photodetectors. In this work, the photodetectors based on transparent conductive oxide (TCO)/Semiconductor/Metal configuration especially with a roughened interface were investigated numerically, and the effect of the roughness on the injection efficiency of hot electrons was analyzed. The simulated results indicate that a roughened structure alleviates effectively the momentum mismatch of hot electrons at the metal/semiconductor interface due to asymmetry factor, and greatly improves the injection efficiency as well as photoresponsivity. At the incidence wavelength of 1550 nm, the photoresponsivity increased by about 8 times. Meanwhile, the influence on the resonant wavelength shift is negligible where the roughness is nano-scale. Our work provides a valuable guidance for the theoretical and experimental research of plasmonic photodetectors.

The thermal evolution process of organic matter is associated with the complete hydrocarbon generation and expulsion process in shale, however, the thermal evolution of organic matter is a long process and cannot be realized without experimental simulations. Although several scholars have substantially studied the thermal evolution of organic matter, it remains a challenging and much debated issue in the studies of organic geochemistry. Volcanic events are crucial in the enrichment of organic matter, and appropriate heating accelerates the thermal evolution of organic matter. However, how strong-rock baking restricts the evolution of organic matter in shale has not been specifically studied. The South Qilian Basin in China is a typical superimposed basin where complex tectonic movements have induced multiple volcanic events, which makes it a favorable location to perform the aforementioned research. This study used the Galedesi Formation shale in the Hala Lake Depression of the South Qilian Basin as an example for investigating the constraints of the volcanic events related to the thermal evolution of organic matter by integrating the results obtained using the geochemical and petrological methods. Our results demonstrate that the lacustrine Galedesi Formation shale of the Hala Lake Depression in the Late Triassic is a typical deep-lake facies deposit with good hydrocarbon generation potential. However, because of the influence of regional tectonic evolution, the burial depth of shale is not deep and the thermal evolution of organic matter is insufficient. Due to the influence of multiple volcanic thermal events in the later stages, the thermal maturity of organic matter in the Galedesi Formation shale generally exceeds 3.0%, which is abnormally high. The apparent carbonization of organic matter can be observed via scanning electron microscopy. Rapid magma baking typically cannot effectively promote the hydrocarbon generation of shale organic matter. Finally, the burial depth of lacustrine shale of the Galedesi Formation in the Hala Lake Depression of South Qilian Basin is too shallow. Organic matter hydrocarbon generation and later shale preservation conditions are not conducive to the enrichment, accumulation, exploration, and development of shale gas.

Mare Fecunditatis is a ~310,000 km2 flat basalt plain located in the low-latitude area of the Moon. Plenty of volcanic features (multiple episodes of mare basalts, sinuous rilles, lava tubes, pyroclastic deposits, domes, irregular mare patches (IMP), ring-moat dome structures (RMDS), floor-fractured craters), tectonic features (grabens and wrinkle ridges), impact-related features, and other features (swirls, pit craters) are identified in Mare Fecunditatis. An in-situ mission to Mare Fecunditatis is scientifically significant to better understand the lunar thermal histories and other questions. All previous in-situ and human missions (Apollo, Luna, Chang’E) were limited to small areas, and no traverse longer than 40 km has been made yet. With the development of technology, long-distance movement will be possible in the future on the lunar surface, providing opportunities to explore multiple sites at one mission with complete documentation of the regional geology. Eight high-value targets (pit crater, IMPs, RMDSs, young basalts, high-Al basalts, pyroclastic deposits, swirls, and fresh craters) were found in Mare Fecunditatis, and a ~1400 km-traverse in 5 years is proposed to explore them to solve the most fundamental lunar questions.