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The indumentum of nutlets is shown to be of phylogenetic importance in previous molecular phylogenetic studies of Paraphlomis, a genus of Lamiaceae with approximately 30 species distributed mainly in southern China and Southeast Asia. Nearly half the species of Paraphlomis are known from limestone areas. In this study, we described and illustrated a new species, P. hsiwenii, from the karst mountain forests in Guangxi Zhuang Autonomous Region, China. Our molecular phylogenetic analyses revealed that P. hsiwenii is recovered in a clade consisting of species with hairy nutlets. The new species is morphologically most similar to P. pagantha from the same clade, but they differ in the morphology of lamina bases, length of pedicels and calyces, as well as the morphology of upper corolla lips.

DC power grid has received increasing attentions recently, and with it comes the demand for highly reliable and stable metering solutions. At present, in the DC distribution projects that have been implemented, some DC metering devices have been put into use. However, from the national and industrial level, there is no clear standard for the design of the metering scheme for the medium and low-voltage DC distribution network, and there is a situation of imperfect metering device configuration. Therefore, based on the analysis of DC metering devices, algorithms and location selection, this paper takes the Hangzhou Jiangdong flexible DC distribution network as an example to analyze the error distribution caused by metering algorithm selection and device configuration. In addition, the influence of harmonics on DC measurement is analyzed to provide the suggestions for DC measurement solutions. The analysis has been verified by MATLAB/Simulink, which provides references for DC metering standards.

Small cell cervical carcinoma (SCCC) is a rare but aggressive malignancy. Here, the authors report human papillomavirus features and genomic landscape in SCCC via high-throughput sequencing methods and identify MYC, SOX, NR4A, ANKRD and CEA family genes as HPV-integrated hotspots.

Multi-agent deep reinforcement learning based on value factorization is one of many multi-agent deep reinforcement learning algorithms,and it is also a research hotspot in the field of multi-agent deep reinforcement learning.Under some constraints,the joint action value function of multi-agent system is factorized into a certain combination of individual action value function,which is able to effectively solve the problems of environment instability and exponential explosion of action space in multi-agent system.Firstly,this paper explains why value function factorization should be carried out and introduces the basic theory of multi-agent deep reinforcement learning.Secondly,according to whether to introduce other mechanisms and the diffe-rence of introduced mechanism,multi-agent deep reinforcement learning(MADRL)algorithm based on value factorization is divi-ded into three categories:simple factorization type,based on the individual-global-max(IGM)principle and based on attention mechanism.Then,according to the classifications,this paper emphatically introduces several typical algorithms and compares and analyzes their strengths and weaknesses.Finally,it briefly describes the application and development prospect of these algorithms.

Flexible strain sensors play an important role in electronic skins, wearable medical devices, and advanced robots. Herein, a highly sensitive and fast response optical strain sensor with two evanescently coupled optical micro/nanofibers (MNFs) embedded in a polydimethylsiloxane (PDMS) film is proposed. The strain sensor exhibits a gauge factor as high as 64.5 for strain ≤ 0.5% and a strain resolution of 0.0012% which corresponds to elongation of 120 nm on a 1 cm long device. As a proof-of-concept, highly sensitive fingertip pulse measurement is realized. The properties of fast temporal frequency response up to 30 kHz and a pressure sensitivity of 102 kPa−1 enable the sensor for sound detection. Such versatile sensor could be of great use in physiological signal monitoring, voice recognition and micro-displacement detection.

Soft and stretchable tactile sensors have received extensive attention for their potential applications in wearables, human–robot interaction, and intelligent robots. Herein, inspired by the functions of skin somatosensory signal generation and processing, an artificial intelligence‐motivated skin‐like optical fiber tactile (SOFT) sensor is proposed. It features multifunctional touch interaction capabilities including tactile amplitude and position and tensile strain. Four fiber Bragg gratings (FBGs) are embedded in a skin‐like three‐layer laminate structure of the SOFT sensor, forming a flexible tactile sensing array with a stretchability larger than 20%. Fusing the two‐level cascaded neural network, the position and magnitude of the contact force can be distinguished simultaneously. The recognition accuracy for contact position is up to 92.41% and the error is less than 4.2% within the force range of 0–3.5 N. Several SOFT sensor‐based interactive applications including pressure password interface and music playback are achieved by combining the artificial intelligence spatiotemporal dynamic logic analysis. Furthermore, the sensor is also capable of complex scenes involving tension and tactile sensing, such as dexterous hand perception and human–robot interaction control. This work provides novel insights into artificial intelligence‐based integrated skin that shows broad promise in intelligent prosthetics and bionic robotic.

Abstract High flexibility, porosity, and antibacterial activity are extremely desired for wearable health monitoring, which is beneficial to simultaneously promote wearing comfort and safety. In this study, an antibacterial nanofibers‐based triboelectric generator (AN‐TENG) composed of the flexible chitosan/polyvinylpyrrolidone modified with halloysite nanotubes (CTS/PVP/HNTs) nanofibers and cube‐arrays structured Ecoflex film is proposed for simultaneously energy harvesting and self‐powered human motion monitoring. The open‐circuit voltage (280 V), short‐circuit current (3.98 μA), and transferred charge (51 nC) of the CTS/PVP/HNTs nanofibers TENG at the optimal compound concentration are increased by 90.8%, 86.92%, and 96.2%, respectively, compared to the CTS/PVP nanofibers one (size: 3 cm × 3 cm, mechanical force: 10 N @1 Hz), revealing good real‐time monitoring ability for human wrist, elbow, and finger motion. An antibacterial test is carried out to evaluate the antibacterial activity and the antibacterial rate of the nanofibers against Escherichia coli (ATCC 8739) and Staphylococcus aureus (ATCC 6538) based on the current national standard GB/T 31402–2015, indicating good antibacterial properties of the nanofibers. This research offers an ingenious strategy to establish an antibacterial nanofibers‐based TENG for self‐powered motion monitoring and energy harvesting and offers a new insight to improve the practical security of wearable electronic devices.

Branching fractions (BFs) of Sm ii for 71 lines from 12 excited levels ranging from 31,638.79 to 35,463.91 cm ^−1 were determined for the first time based on the Fourier transform spectra available from the National Solar Observatory database. New transition probabilities and oscillator strengths for these lines were derived by combining the determined BFs with reliable lifetimes measured using a time-resolved laser-induced fluorescence technique. Furthermore, BFs for 38 lines from five levels included in earlier studies were also determined for comparisons. The new results reported in this work will be useful in many fields, especially for astrophysics.

The interaction of fullerenes and their derivatives with environmental molecules such as oxygen or water was crucial for the rational design of low-dimensional materials and devices. In this paper, the near-edge X-ray absorption fine structure (NEXAFS), X-ray emission spectroscopy (XES) and X-ray photoelectron spectroscopy (XPS) shake-up satellites were employed to distinguish the oxides and hydrates of the fullerene C60 and azafullerene C59N families. The study includes various isomers, such as the open [5,6] and closed [6,6] isomers of C60O, C60H(OH), C60-O-C60, C60H-O-C60H, C59N(OH) and C59N-O-C59N, based on density functional theory. These soft X-ray spectra offered comprehensive insights into the molecular orbitals of these azafullerene molecular groups. The oxygen K-edge NEXAFS, carbon and oxygen K-edge XPS shake-up satellite spectra provided valuable tools for distinguishing oxides or hydrates of fullerene C60 and azafullerene C59N. Our findings could significantly benefit the development of fullerene functional molecular materials and expand the application scope of soft X-ray spectroscopy as a molecular fingerprinting tool for the fullerene family.

The carrier eccentricity error and gear compound faults are most likely to occur simultaneously in an actual planetary gear train (PGT). Various faults and errors are coupled with each other to generate a complex dynamic response, which makes the diagnosis of PGT faults difficult in practice. In order to analyze the joint effect of the error and the compound faults in a PGT, a carrier eccentricity error model is proposed and incorporated into the TVMS model by considering the time-varying center distance, line of action (LOA), meshing angle, and contact ratio. Then, the TVMS of the cracked gear is derived based on the potential energy method. On this basis, the dynamic model of a PGT with both the carrier eccentricity error and compound gear cracks as internal excitations are established. Furthermore, the meshing characteristics and dynamic responses of the PGT are simulated to investigate the compound fault features. A series of experiments are conducted to further analyze the influence of the compound fault on the vibration response. The relevant conclusions can provide a reference for the compound fault diagnosis of a PGT in practice.

The identification of compound fault components of a planetary gearbox is especially important for keeping the mechanical equipment working safely. However, the recognition performance of existing deep learning-based methods is limited by insufficient compound fault samples and single label classification principles. To solve the issue, a capsule neural network with an improved feature extractor, named LTSS-BoW-CapsNet, is proposed for the intelligent recognition of compound fault components. Firstly, a feature extractor is constructed to extract fault feature vectors from raw signals, which is based on local temporal self-similarity coupled with bag-of-words models (LTSS-BoW). Then, a multi-label classifier based on a capsule network (CapsNet) is designed, in which the dynamic routing algorithm and average threshold are adopted. The effectiveness of the proposed LTSS-BoW-CapsNet method is validated by processing three compound fault diagnosis tasks. The experimental results demonstrate that our method can via decoupling effectively identify the multi-fault components of different compound fault patterns. The testing accuracy is more than 97%, which is better than the other four traditional classification models.

Vegetation greenness change is the result of the combination of natural and anthropogenic factors. Understanding how these factors individually and collectively affect vegetation dynamics and whether their spatial heterogeneity has any effect on vegetation greenness change is the crucial investigation area. Previous studies revealed the distinct characteristics of spatial and temporal heterogeneity in the impact factors influencing vegetation greenness change across various regions, often assuming a linear contribution mechanism between vegetation greenness change and these drivers. However, such a simplistic assumption fails to adequately capture the real-world dynamics of vegetation greenness change. Thus, this study firstly used geographical detector (Geodetector) to quantitatively measure the contribution of each factor to vegetation greenness change considering spatial heterogeneity in the Yangtze River Economic Belt (YREB) during the growing season from 2000 to 2020, then selecting significant factors from numerous drivers with the recursive feature elimination algorithm combined with a random forest model (RFE-RF), which is able to reduce redundant features in the data and prevent overfitting. Finally, four stable impact factors and the spatial heterogeneity of some factors contributing to vegetation greenness change were identified. The results show that approximately 83% of the regional vegetation has shown an overall increasing trend, while areas undergoing rapid development predominantly experienced a decline in greenness. Single factor screened by Geodetector with the explanatory power greater than 10% for vegetation greenness change included temperature (Tem), population density (PD), the land-use/land-cover (LULC), DEM, wind speed, and slope. The RFE-RF method identified precipitation (Pre) and CO2 emissions as additional influential factors for vegetation greenness change, in addition to the first four factors mentioned previously. These findings suggest that the four stable factors consistently influence vegetation greenness change. Combined with the principles of the algorithms and the above results, it was found that the spatial heterogeneity of wind speed and slope has an effect on vegetation greenness change, whereas the spatial heterogeneity of Pre and CO2 emissions has minimal effect.

Abstract With the advancement of information technology and the reduction of costs, the application of unmanned aerial vehicle (UAV) has gradually expanded from the military field to the industrial field and civilian field. It brings great convenience to people in surveillance, detection, transportation, emergency rescue etc. However, UAVs usually work in harsh natural environments, and their communication security confronts various challenges. Due to UAVs' limited resources, such as computing capability, storage space, and energy, traditional security protection schemes based on complex cryptographic algorithms are not suitable for UAV systems directly. Therefore, a two‐stage lightweight identity authentication and key agreement protocol for UAV is proposed in this paper. The entire process only uses hash and XOR operations, which significantly improves the authentication efficiency. Simultaneously, the physical unclonable function (PUF) is introduced and embedded into the UAV hardware to ensure UAV network communication security when a UAV suffers a physical capture attack. In the paper, the security of the proposed protocol is proved with Burrows–Abadi–Needham (BAN) logic, Real‐or‐Random (ROR) model, and AVISPA simulation tools. An informal security analysis is also provided to illustrate that the protocol satisfies the security requirements of UAV networks. Finally, the protocol is compared with other existing protocols regarding function properties, computation cost, and communication cost, which shows that the proposed protocol has effectiveness and practicality.

Abstract The use of deuterium are critical for promoting the fundamental understanding of aggregate materials and their new functions. Particularly, the solution structure of conjugated polymers can be hardly resolved without deuteration. However, studies about the isotopic effects of casting solvents on the aggregated structures of photovoltaic polymers and their bulk‐heterojunction blends are deficient. Here, the impact of deuterated solvents on the thermal behavior, aggregated structures, and device performance of photovoltaic polymers is clearly delineated for the first time by multiple techniques. The enhanced π‐π stacking order of photovoltaic polymers is highly relevant to their relatively poor miscibility with deuterated solvents. Benefiting from higher crystallinity and optimized morphology of deuterated solvents processed films, the devices are able to achieve better efficiency and notable improvement in thermal stability. Our results highlight the isotopic effects of solvents on the aggregated structure of conjugated polymer systems and reveal the potential of innovative approaches to fabricate thermally stable high‐efficiency solar cells.

Abstract Graphene is a promising candidate for the next‐generation infrared array image sensors at room temperature due to its high mobility, tunable energy band, wide band absorption, and compatibility with complementary metal oxide semiconductor process. However, it is difficult to simultaneously obtain ultrafast response time and ultrahigh responsivity, which limits the further improvement of graphene photoconductive devices. Here, a novel graphene/C60/bismuth telluride/C60/graphene vertical heterojunction phototransistor is proposed. The response spectral range covers 400–1800 nm; the responsivity peak is 106 A W−1; and the peak detection rate and peak response speed reach 1014 Jones and 250 µs, respectively. In addition, the regulation of positive and negative photocurrents at a gate voltage is characterized and the ionization process in impurities of the designed phototransistor at a low temperature is analyzed. Tunable bidirectional response provides a new degree of freedom for phototransistors' signal resolution. The analysis of the dynamic change process of impurity energy level is conducted to improve the device's performance. From the perspective of manufacturing process, the ultrathin phototransistor (20–30 nm) is compatible with functional metasurface to realize wavelength or polarization selection, making it possible to achieve large‐scale production of integrated spectrometer or polarization imaging sensor by nanoimprinting process.

ObjectiveTo understand the current situation and existing problems of the food safety risk monitoring ability of CDC at all levels in Jiangxi Province， and provide basis for further improving.MethodsThe basic information， personnel allocation， testing ability and personnel training of CDC at all levels in Jiangxi Province were investigated by self-filled questionnaire survey.ResultsA total of 97 CDCs at all levels were investigated in Jiangxi Province， among which 43 CDCs at county （district） level did not obtain qualification certification. The average area of the provincial CDC was 3 495 m2， and the average laboratory area was 968 m2. There were 1 091 people engaged in food related activities in the provincial CDC， mainly technical personnels， accounting for 75%； The composition characteristics of technical personnels and quality management personnels were basically the same： bachelor’s degree， more than 6 years experience， 30-50 years old personnels accounted for the highest proportion. The overall monitoring capacity of CDCs in the province was weak. Except for the provincial level， the average food detection capacity of CDCs at city and county （district） level didn’t meet the national requirements. In 2018， a total of 1 430 training was received in the province， with an average 1.3 training per person per year.ConclusionIn Jiangxi Province， the talent team construction of CDC at all levels needs to be strengthened， and it is urgent to expand the staff team of CDC at local level， especially to improve the proportion of highly educated talents. The monitoring capacity needs to be improved， and the passing rate of certification of inspection and testing institutions of county （district） level CDC institutions needs to be improved.

Abstract Objectives Smokers or never smokers exposed to environmental tobacco use are usually associated with various diseases and cancers. In order to better help college students prevent the tobacco use and thus lower the incidence of avoidable diseases, this study explored the predictive power of different variables including demographic and psychological variables in relation to smoking behaviors. Methods Maslach Burnout Inventory-Student Survey and Kessler Psychological Distress Scale (K10) were used in this study. Results There were 1449 college students participating in the study with 1340 pieces of valid data left, the effective ratio was 92.48%. The valid data included 37.1% male and 62.9% female aged 18.83 on average with 1.55 standard deviation. The multivariate logistic regression indicated that college students who were male (versus female, OR = 9.55), majoring in medicine and sports (versus nursing, ORmedicine = 2.19, ORsports = 2.81), born in the non-singleton family (versus singleton family, OR = 0.63) with higher family income (versus lower family income, OR = 0.45), surrounded with smoking friends (versus without smoking friends, OR = 0.18), were more vulnerable to smoke. In addition, combined with the theory of planned behavior, the dimensions of learning burnout had full mediation effects between psychological distress and smoking behavior. Conclusions Psychological distress can only indirectly affect smoking behavior via learning efficacy, cynicism and emotional exhaustion. Adjustments from different dimensions of learning burnout such as avoiding cynicism about learning, enhancing learning efficacy and emotion exhaustion will help college students better prevent the tobacco use.

Sensors based on personalized healthcare systems have been widely used in the medical field. However, energy limitations have greatly hindered the further development of medical sensors. For the traditional Medium Access Control (MAC) protocol, the duration of low-power listening is fixed because it ignores that the available energy of sensors is different in some situations, which leads to a high delay and low energy utilization. In this paper, a Maximum Listening Length MAC (MLL-MAC) protocol is proposed to fully utilize the energy in the sensor-based systems. The MLL-MAC protocol is an improvement of the Receiver-Initiated (RI) MAC protocol. The main advance is that the sensor node performs the following additional operations: (1) The sender sends a beacon when it wakes up and sends data, thus establishing a communication link with the receiver in the listening state; (2) The receiver keeps listening as long as possible to reduce the delay when it wakes up and listens to the channel, which is different from the previous strategy in which the node turns into a sleep state immediately without receiving data. Furthermore, the sensor node can dynamically determine whether to send beacons and prolong listening duration according to its available energy level. The MLL-MAC protocol is evaluated through theoretical analysis and experimental results. The results show that, compared with the RI-MAC protocol, the MLL-MAC protocol can reduce the average end-to-end delay by 41.4% and improve the energy utilization by 15.1%.

With high incidence rate, cancer is the main cause of death in humans. Non-coding RNAs, as novel master regulators, especially long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), play important roles in the regulation of tumorigenesis. lncRNA NEAT1 has recently gained much attention, as it is dysregulated in a broad spectrum of cancers, where it acts as either an oncogene or a tumor suppressor gene. Accumulating evidence shows that NEAT1 is correlated with the process of carcinogenesis, including proliferation, invasion, survival, drug resistance, and metastasis. NEAT1 is considered to be a biomarker and a novel therapeutic target for the diagnosis and prognosis of different cancer types. The mechanisms by which NEAT1 plays a critical role in cancers are mainly via interactions with miRNAs. NEAT1-miRNA regulatory networks play significant roles in tumorigenesis, which has attracted much attention from researchers around the world. In this review, we summarize the interaction of NEAT1 with miRNAs in the regulation of protein-coding genes in cancer. A better understanding of the NEAT1-miRNA interactions in cancer will help develop new diagnostic biomarkers and therapeutic approaches.

Multi-wavelength imaging ability is important for bio-imaging, to obtain multi-modal information of biological activities. We propose a multi-wavelength super-resolution imaging method, employing the Bloch surface waves (BSWs) supported by one-dimensional photonic crystal as subwavelength structured illumination fields. Here 488 nm (blue), 532 nm (green), and 632.8 nm (red) are chosen as the illumination wavelengths, and a two-dimensional equilateral triangular grating is designed to couple the incident plane waves to the BSWs in the all-dielectric photonic crystal. The triangular grating ensures a more uniform resolution improvement along with whole lateral directions and provides better imaging quality compared with lattice grating. In our demonstration, the resolution improvements are above 2.4 fold for the three wavelengths, and lateral resolutions are below 120 nm in the Rayleigh criterion. Moreover, as the illumination device is composed of a periodic planar structure, the larger field of view is achievable. The proposed method could achieve multi-wavelength wide-field super-resolution surface imaging while maintaining high speed, good imaging quality and bio-compatibility.

With the rapid increase of distributed photovoltaic (PV) power integrating into the distribution network (DN), the critical issues such as PV power curtailment and low equipment utilization rate have been caused by PV power fluctuations. DN has less controllable equipment to manage the PV power fluctuation. To smooth the power fluctuations and further improve the utilization of PV, the regulation ability from the demand-side needs to be excavated. This study presents a continuous control method of the feeder load power in a DN based on the voltage regulation to respond to the rapid fluctuation of the PV power output. PV power fluctuations will be directly reflected in the point of common coupling (PCC), and the power fluctuation rate of PCCs is an important standard of PV curtailment. Thus, a demand-side management strategy based on model predictive control (MPC) to mitigate the PCC power fluctuation is proposed. In pre-scheduling, the intraday optimization model is established to solve the reference power of PCC. In real-time control, the pre-scheduling results and MPC are used for the rolling optimization to control the feeder load demand. Finally, the data from the field measurements in Guangzhou, China are used to verify the effectiveness of the proposed strategy in smoothing fluctuations of the distributed PV power.

Metasurfaces, which are ultrathin planar artificial materials flexibly controlling the phase, amplitude, and polarization of the light, have facilitated the high integration and miniaturization of hyperspectral imaging systems. However, the pushbroom hyperspectral imaging systems based on metasurfaces usually face the large smile and keystone, which reduces the spectral uniformity and the fidelity of the spectral information. Moreover, the employment of many metasurfaces would cause manufacturing difficulties. In this paper, a planar hyperspectral imager only using two metasurfaces is proposed to achieve a spectral resolution of 3.5 nm in 850-1000 nm band with the near diffraction-limited focusing capability, and its maximum of smile and keystone reach to 124.4 μm and 33.6 μm for the image plane size of 4.75 mm × 1.35 mm and pixel size of 26 μm × 26 μm, respectively. This imager can provide a promising avenue for portable environmental monitoring systems and wearable electronic consumer products.

Humanoid tactility has been boosting robotic intelligence in object recognition, dexterous manipulation, and human–robot interaction. For many artificial tactile sensors, especially those based on optical principles, inflexibility, bulkiness, and monomodality limit their potential to function as humanoid skins. Herein, by embedding lab‐made optical nanofibers (ONFs) into elastomeric films, soft, flexible, thin (around 500 μm, similar to human skin), and multimodal (force and thermosensitive) robotic skins are achieved. These superior characteristics arise from the low flexural rigidity and large evanescent field of ONFs, due to their subwavelength diameters (down to 450 nm). By tuning light wavelength, ONF diameter, and skin thickness, variable sensitivities and sensing ranges for both force and temperature are reported. Depending on different sensing requirements, special modules can be further assembled on the ONF skins for various surface properties, including hardness, texture, and thermal conductivity. The ONF skins can enable a commercial robot to emulate human behaviors, including adaptive grasping of flimsy objects, contactless temperature measurement, and even the perception of leaf veins. It is anticipated that these ONF skins could offer a unique solution in multiple intelligent systems such as robotics, prosthetics, human–machine interface and wearable devices.

To achieve low wavefront error and high throughput with vignetting-free target simulators, a concave-convex-concaveoff-axis spherical system is designed in this paper, which effectively eliminates astigmatism and coma of the system by fields of view (FOVs) and aperture offset and provides theoretical basis for the realization of 100% matching between the exit pupil of the field lens and entrance pupil of the three-mirror anastigmat (TMA) system. Only spherical mirror element is used in this target simulator, which not only reduces the difficulty of manufacturing and cost but also greatly reduces the difficulty of assembling and adjusting. It provides an effective scheme for the design of target simulator and has strong engineering application value.

Summary: Cervical cancer (CC) that is caused by high-risk human papillomavirus (HPV) remains a significant public health problem worldwide. HPV integration sites can be silent or actively transcribed, leading to the production of viral-host fusion transcripts. Herein, we demonstrate that only productive HPV integration sites were nonrandomly distributed across both viral and host genomes, suggesting that productive integration sites are under selection and likely to contribute to CC pathophysiology. Furthermore, using large-scale, multi-omics (clinical, genomic, transcriptional, proteomic, phosphoproteomic, and single-cell) data, we demonstrate that tumors with productive HPV integration are associated with higher E6/E7 proteins and enhanced tumor aggressiveness and immunoevasion. Importantly, productive HPV integration increases from carcinoma in situ to advanced disease. This study improves our understanding of the functional consequences of HPV fusion transcripts on the biology and pathophysiology of HPV-driven CCs, suggesting that productive HPV integration should be evaluated as an indicator of high risk for progression to aggressive cancers.

Pseudogenes are important resources for investigation of genome evolution and genomic diversity because they are nonfunctional but have regulatory effects that influence plant adaptation and diversification. However, few systematic comparative analyses of pseudogenes in closely related species have been conducted. Here, we present a turnip (Brassica rapa ssp. rapa) genome sequence and characterize pseudogenes among diploid Brassica species/subspecies. The results revealed that the number of pseudogenes was greatest in Brassica oleracea (CC genome), followed by B. rapa (AA genome) and then Brassica nigra (BB genome), implying that pseudogene differences emerged after species differentiation. In Brassica AA genomes, pseudogenes were distributed asymmetrically on chromosomes because of numerous chromosomal insertions/rearrangements, which contributed to the diversity among subspecies. Pseudogene differences among subspecies were reflected in the flavor-related glucosinolate (GSL) pathway. Specifically, turnip had the highest content of pungent substances, probably because of expansion of the methylthioalkylmalate synthase-encoding gene family in turnips; these genes were converted into pseudogenes in B. rapa ssp. pekinensis (Chiifu). RNA interference-based silencing of the gene encoding 2-oxoglutarate-dependent dioxygenase 2, which is also associated with flavor and anticancer substances in the GSL pathway, resulted in increased abundance of anticancer compounds and decreased pungency of turnip and Chiifu. These findings revealed that pseudogene differences between turnip and Chiifu influenced the evolution of flavor-associated GSL metabolism-related genes, ultimately resulting in the different flavors of turnip and Chiifu.

Abstract Background To date, there is no approved blood‐based biomarker for breast cancer detection. Herein, we aimed to assess semaphorin 4C (SEMA4C), a pivotal protein involved in breast cancer progression, as a serum diagnostic biomarker. Methods We included 6,213 consecutive inpatients from Tongji Hospital, Qilu Hospital, and Hubei Cancer Hospital. Training cohort and two validation cohorts were introduced for diagnostic exploration and validation. A pan‐cancer cohort was used to independently explore the diagnostic potential of SEMA4C among solid tumors. Breast cancer patients who underwent mass excision prior to modified radical mastectomy were also analyzed. We hypothesized that increased pre‐treatment serum SEMA4C levels, measured using optimized in‐house enzyme‐linked immunosorbent assay kits, could detect breast cancer. The endpoints were diagnostic performance, including area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. Post‐surgery pathological diagnosis was the reference standard and breast cancer staging followed the TNM classification. There was no restriction on disease stage for eligibilities. Results We included 2667 inpatients with breast lesions, 2378 patients with other solid tumors, and 1168 healthy participants. Specifically, 118 patients with breast cancer were diagnosed with stage 0 (5.71%), 620 with stage I (30.00%), 966 with stage II (46.73%), 217 with stage III (10.50%), and 8 with stage IV (0.39%). Patients with breast cancer had significantly higher serum SEMA4C levels than benign breast tumor patients and normal controls (P < 0.001). Elevated serum SEMA4C levels had AUC of 0.920 (95% confidence interval [CI]: 0.900–0.941) and 0.932 (95%CI: 0.911–0.953) for breast cancer detection in the two validation cohorts. The AUCs for detecting early‐stage breast cancer (n = 366) and ductal carcinoma in situ (n = 85) were 0.931 (95%CI: 0.916–0.946) and 0.879 (95%CI: 0.832–0.925), respectively. Serum SEMA4C levels significantly decreased after surgery, and the reduction was more striking after modified radical mastectomy, compared with mass excision (P < 0.001). The positive rate of enhanced serum SEMA4C levels was 84.77% for breast cancer and below 20.75% for the other 14 solid tumors. Conclusions Serum SEMA4C demonstrated promising potential as a candidate biomarker for breast cancer diagnosis. However, validation in prospective settings and by other study groups is warranted.

Phytoremediation that depends on excellent plant resources and effective enhancing measures is important for remediating heavy metal-contaminated soils. This study investigated the cadmium (Cd) tolerance and accumulation characteristics of Dahlia pinnata Cav. to evaluate its Cd phytoremediation potential. Testing in soils spiked with 5–45 mg kg–1 Cd showed that D. pinnata has a strong Cd tolerance capacity and appreciable shoot Cd bioconcentration factors (0.80–1.32) and translocation factors (0.81–1.59), indicating that D. pinnata can be defined as a Cd accumulator. In the rhizosphere, Cd stress (45 mg kg–1 Cd) did not change the soil physicochemical properties but influenced the bacterial community composition compared to control conditions. Notably, the increased abundance of the bacterial phylum Patescibacteria and the dominance of several Cd-tolerant plant growth–promoting rhizobacteria (e.g., Sphingomonas, Gemmatimonas, Bryobacter, Flavisolibacter, Nocardioides, and Bradyrhizobium) likely facilitated Cd tolerance and accumulation in D. pinnata. Comparative transcriptomic analysis showed that Cd significantly induced (P < 0.001) the expression of genes involved in lignin synthesis in D. pinnata roots and leaves, which are likely to fix Cd2+ to the cell wall and inhibit Cd entry into the cytoplasm. Moreover, Cd induced a sophisticated signal transduction network that initiated detoxification processes in roots as well as ethylene synthesis from methionine metabolism to regulate Cd responses in leaves. This study suggests that D. pinnata can be potentially used for phytoextraction and improves our understanding of Cd-response mechanisms in plants from rhizospheric and molecular perspectives.

Tumor heterogeneity significantly increases the difficulty of tumor treatment. The same drugs and treatment methods have different effects on different tumor subtypes. Therefore, tumor heterogeneity is one of the main sources of poor prognosis, recurrence and metastasis. At present, there have been some computational methods to study tumor heterogeneity from the level of genome, transcriptome, and histology, but these methods still have certain limitations. In this study, we proposed an epistasis and heterogeneity analysis method based on genomic single nucleotide polymorphism (SNP) data. First of all, a maximum correlation and maximum consistence criteria was designed based on Bayesian network score K2 and information entropy for evaluating genomic epistasis. As the number of SNPs increases, the epistasis combination space increases sharply, resulting in a combination explosion phenomenon. Therefore, we next use an improved genetic algorithm to search the SNP epistatic combination space for identifying potential feasible epistasis solutions. Multiple epistasis solutions represent different pathogenic gene combinations, which may lead to different tumor subtypes, that is, heterogeneity. Finally, the XGBoost classifier is trained with feature SNPs selected that constitute multiple sets of epistatic solutions to verify that considering tumor heterogeneity is beneficial to improve the accuracy of tumor subtype prediction. In order to demonstrate the effectiveness of our method, the power of multiple epistatic recognition and the accuracy of tumor subtype classification measures are evaluated. Extensive simulation results show that our method has better power and prediction accuracy than previous methods.

BackgroundFor severe spontaneous intracerebral hemorrhage (sSICH) patients with high risk of ischemic events, the incidence of postoperative major cardiovascular/cerebrovascular and peripheral vascular events (MACCPE) is notable. Although antiplatelet therapy is a potential way to benefit these patients, the severe hemorrhagic complications, e.g., intracranial re-hemorrhage, is a barrier for early starting antiplatelet therapy.ObjectivesThis randomized controlled trial aims to identify the benefit and safety of early starting antiplatelet therapy after operation for sSICH patients with high risk of ischemic events.MethodsThis study is a multicenter, prospective, randomized, open-label, blinded-endpoint trial. We will enroll 250 sSICH patients with a high risk of ischemic events (including cerebral infarcts, transient ischemic attack, myocardial infarction, pulmonary embolism, and deep venous thrombosis). The participants will be randomized in a 1:1 manner to early-start group (start antiplatelet therapy at 3 days after operation) and normal-start group (start antiplatelet therapy at 30 days after operation). The early-start group will receive aspirin 100 mg daily. The control group will not receive antithrombotic therapy until 30 days after operation. The efficacy endpoint is the incidence of MACCPE, and the safety endpoint is the incidence of intracranial re-hemorrhage.DiscussionThe Early-Start antiplatelet therapy after operation in patients with spontaneous intracerebral hemorrhage trial (E-start) is the first randomized trial about early start antiplatelet therapy for operated sSICH patients with a high risk of ischemic events. This study will provide a new strategy and evidence for postoperative management in the future.Clinical trial registrationClinicalTrials.gov, identifier NCT04820972; Available at: https://clinicaltrials.gov/ct2/show/NCT04820972?term=NCT04820972&draw=2&rank=1.Chinese Clinical Trial Registry, identifier ChiCTR2100044560; Available at: http://www.chictr.org.cn/showproj.aspx?proj=123277.

Background: Atopic dermatitis (AD) is a chronic and recurrent skin disease. At present, there is a lack of sufficiently effective and safe medicines that can be used for a prolonged time and reduce the recurrence of AD. The Gu-Ben-Hua-Shi (AESS) formula has been used for many years with a good clinical effect on AD but its specific treatment mechanism is unknown.Methods: The main components of AESS were analyzed using ultra-high performance liquid chromatography (UPLC). The composition of AESS compounds in the serum from rats was analyzed using ultra-high performance liquid chromatography-mass spectrometry. An AD mouse model was constructed using 2,4-dinitrofluorobenzene stimulation in Balb/C mice and the effect on the reduction of skin lesions and Th1/Th2/Th17/Treg balance after AESS administration were measured. The effects of AESS serum on the proliferation and apoptosis of keratinocyte cell line HaCaT and adhesion of HaCaT to human monocyte cell line THP-1 were detected in an IFN-γ/TNF-α stimulated AD-like inflammatory cell model. The effects of Yes-associated protein (YAP) expression on the therapeutic effect and a related signaling pathway were also investigated.Results: In total, 10 components were confirmed using UPLC, namely five organic acids, three flavonoids, and two chromogenic ketones. Additionally, the similarity of the three batches of samples (S1–3) was above 0.98, indicating that the formula samples have good uniformity. These 10 compounds were also detected in rat serum, suggesting that they are absorbed into rat blood as prototype components. Furthermore, AESS effectively reduced the skin lesions in the AD mouse model, regulated the Th1/Th2/Th17/Treg imbalance, improved the proliferation ability of the AD-like cell model, and inhibited HaCaT apoptosis and adhesion to THP-1 cells. It also reduced the expression of YAP in Th17 and Treg cells of the mouse spleen and increased YAP expression in the skin. The change in YAP expression in keratinocytes weakened the curative effect of AESS, and AESS exerted its effects through the NF-κB signaling pathway.Conclusion: AESS may play a role in the treatment of AD by affecting the expression of YAP. These findings can be used to promote its use as an alternative medication for prolonged use with fewer side effects.

Existing zero-shot learning (ZSL) methods typically focus on mapping from the feature space (e.g., visual space) to class-level attributes, often leading to a non-injective projection. Such a mapping may cause a significant loss of instance-level information. While an ideal projection to instance-level attributes would be desirable, it can also be prohibitively expensive and thus impractical in many scenarios. In this work, we propose a variational disentangle zero-shot learning (VDZSL) framework that addresses this problem by constructing variational instance-specific attributes from a class-specific semantic latent distribution. Specifically, our approach disentangles each instance into class-specific attributes and the corresponding variant features. Unlike transductive ZSL, which assumes that unseen classes’ attributions are known beforehand, our VDZSL method does not rely on this strong assumption, making it more applicable in real-world scenarios. Extensive experiments conducted on three popular ZSL benchmark datasets (i.e., AwA2, CUB, and FLO) validate the effectiveness of our approach. In the conventional ZSL setting, our method demonstrates an improvement of 12∼15% relative to the advanced approaches and achieves a classification accuracy of 70% on the AwA2 dataset. Furthermore, under the more challenging generalized ZSL setting, our approach can gain an improvement of 5∼15% compared with the advanced methods.

The pharmacokinetic variability of nifedipine widely observed in the clinic cannot be fully explained by pharmacogenomics. As a new factor affecting drug metabolism, how the gut microbiota affects the pharmacokinetics of nifedipine needs to be explored. Spontaneously hypertensive rats (SHRs) have been commonly used in hypertension-related research and served as the experimental groups; Wistar rats were used as control groups. In this study, the bioavailability of nifedipine decreased by 18.62% (p < 0.05) in the SHRs compared with the Wistar rats. Changes in microbiota were associated with the difference in pharmacokinetics. The relative abundance of Bacteroides dorei was negatively correlated with AUC0–t (r = −0.881, p = 0.004) and Cmax (r = −0.714, p = 0.047). Analysis of serum bile acid (BA) profiles indicated that glycoursodeoxycholic acid (GUDCA) and glycochenodeoxycholic acid (GCDCA) were significantly increased in the SHRs. Compared with the Wistar rats, the expressions of CYP3A1 and PXR were upregulated and the enzyme activity of CYP3A1 increased in the SHRs. Spearman’s rank correlation revealed that Bacteroides stercoris was negatively correlated with GUDCA (r = −0.7126, p = 0.0264) and GCDCA (r = −0.6878, p = 0.0339). Moreover, GUDCA was negatively correlated with Cmax (r = −0.556, p = 0.025). In primary rat hepatocytes, GUDCA could induce the expressions of PXR target genes CYP3A1 and Mdr1a. Furthermore, antibiotic treatments in SHRs verified the impact of microbiota on the pharmacokinetics of nifedipine. Generally, gut microbiota affects the pharmacokinetics of nifedipine through microbial biotransformation or by regulating the enzyme activity of CYP3A1.

Chilies undergo multiple stages from field production to reaching consumers, making them susceptible to contamination with foreign materials. Visually similar foreign materials are difficult to detect manually or using color sorting machines, which increases the risk of their presence in the market, potentially affecting consumer health. This paper aims to enhance the detection of visually similar foreign materials in chilies using hyperspectral technology, employing object detection algorithms for fast and accurate identification and localization to ensure food safety. First, the samples were scanned using a hyperspectral camera to obtain hyperspectral image information. Next, a spectral pattern recognition algorithm was used to classify the pixels in the images. Pixels belonging to the same class were assigned the same color, enhancing the visibility of foreign object targets. Finally, an object detection algorithm was employed to recognize the enhanced images and identify the presence of foreign objects. Random forest (RF), support vector machine (SVM), and minimum distance classification algorithms were used to enhance the hyperspectral images of the samples. Among them, RF algorithm showed the best performance, achieving an overall recognition accuracy of up to 86% for randomly selected pixel samples. Subsequently, the enhanced targets were identified using object detection algorithms including R-CNN, Faster R-CNN, and YoloV5. YoloV5 exhibited a recognition rate of over 96% for foreign objects, with the shortest detection time of approximately 12 ms. This study demonstrates that the combination of hyperspectral imaging technology, spectral pattern recognition techniques, and object detection algorithms can accurately and rapidly detect challenging foreign objects in chili peppers, including red stones, red plastics, red fabrics, and red paper. It provides a theoretical reference for online batch detection of chili pepper products, which is of significant importance for enhancing the overall quality of chili pepper products. Furthermore, the detection of foreign objects in similar particulate food items also holds reference value.

[Abstract]: Talents are the first resources that drive societal progress and scientific advances. A great amount of outstanding medical talent is required for development with the times, societal progress, and assurance and improvement of national health levels. The national development strategy for the Guangdong-Hong Kong-Macau Greater Bay Area fully utilizes the strengths in medical resources and pilot testing of Macau, Hong Kong, and Guangdong to promote the upgrading of the medical industry. Guangdong Pharmaceutical University is located in the Guangdong-Hong Kong-Macau Greater Bay Area and focuses on drugs, medical integration, and its mission is to nurture outstanding medical talents. Dr. Guo, the dean of the university, proposed the idea of “integrated pharmacy” based on the theoretical foundation of “integrative medicine” by an academician, Dr. Daiming Fan. In 2016, Guangdong Pharmaceutical University was the first to open a School of Integrated Pharmacy and Integrated Pharmacy Research Institute in China, established the integrated pharmacy profession, and obtained a series of achievements. In this paper, we analyzed the strengths of the Guangdong-Hong Kong-Macau Greater Bay Area and combined it with the integrated pharmacy talent development experience of Guangdong Pharmaceutical University to propose a new “talents of integrative medicine and pharmacy” development concept and actively explored the “talents of integrative medicine and pharmacy” innovative development model. This will contribute to healthcare industry development in China and the Guangdong-Hong Kong-Macau Greater Bay Area.

Screening for superior cadmium (Cd) phytoremediation resources and uncovering the mechanisms of plant response to Cd are important for effective phytoremediation of Cd-polluted soils. In this study, the characteristics of Coreopsis grandiflora related to Cd tolerance and accumulation were analyzed to evaluate its Cd phytoremediation potential. The results revealed that C. grandiflora can tolerate up to 20 mg kg−1 of Cd in the soil. This species showed relatively high shoot bioconcentration factors (1.09–1.85) and translocation factors (0.46–0.97) when grown in soils spiked with 5–45 mg kg–1 Cd, suggesting that C. grandiflora is a Cd accumulator and can potentially be used for Cd phytoextraction. Physiological analysis indicated that antioxidant enzymes (i.e., superoxide dismutase, peroxidase, and catalase) and various free amino acids (e.g., proline, histidine, and methionine) participate in Cd detoxification in C. grandiflora grown in soil spiked with 20 mg kg–1 of Cd (Cd20). The overall microbial richness and diversity remained similar between the control (Cd0) and Cd20 soils. However, the abundance of multiple rhizospheric microbial taxa was altered in the Cd20 soil compared with that in the Cd0 soil. Interestingly, many plant growth-promoting microorganisms (e.g., Nocardioides, Flavisolibacter, Rhizobium, Achromobacter, and Penicillium) enriched in the Cd20 soil likely contributed to the growth and vitality of C. grandiflora under Cd stress. Among these, some microorganisms (e.g., Rhizobium, Achromobacter, and Penicillium) likely affected Cd uptake by C. grandiflora. These abundant plant growth-promoting microorganisms potentially interacted with soil pH and the concentrations of Cd and AK in soil. Notably, potassium-solubilizing microbes (e.g., Rhizobium and Penicillium) may effectively solubilize potassium to assist Cd uptake by C. grandiflora. This study provides a new plant resource for Cd phytoextraction and improves our understanding of rhizosphere-associated mechanisms of plant adaptation to Cd-contaminated soil.

BackgroundDe novo deletion of the neuronal calcium-binding protein 2 (NECAB2) locus is associated with idiopathic autism spectrum disorders (ASDs). The in vivo function of NECAB2 in the brain remains largely elusive.MethodsWe investigated the morphological and behavioral profiles of both necab2 knock-out and overexpression zebrafish models. The expression pattern and molecular role of necab2 were probed through a combination of in vitro and in vivo assays.ResultsWe show that Necab2 is a neuronal specific, cytoplasmic, and membrane-associated protein, abundantly expressed in the telencephalon, habenula, and cerebellum. Necab2 is distributed peri-synaptically in subsets of glutamatergic and GABAergic neurons. CRISPR/Cas9-generated necab2 knock-out zebrafish display normal morphology but exhibit a decrease in locomotor activity and thigmotaxis with impaired social interaction only in males. Conversely, necab2 overexpression yields behavioral phenotypes opposite to the loss-of-function. Proteomic profiling uncovers a role of Necab2 in modulating signal transduction of G-protein coupled receptors. Specifically, co-immunoprecipitation, immunofluorescence, and confocal live-cell imaging suggest a complex containing NECAB2 and the metabotropic glutamate receptor 1 (mGluR1). In vivo measurement of phosphatidylinositol 4,5-bisphosphate further substantiates that Necab2 promotes mGluR1 signaling.ConclusionsNecab2 regulates psychomotor and social behavior via modulating a signaling cascade downstream of mGluR1.

The species in the genus Cypripedium (Orchidaceae) are considered endangered, mainly distributed in the temperate regions of the Northern Hemisphere, with high ornamental and economic value. Despite previous extensive studies based on both morphology and molecular data, species and sections relationships within Cypripedium remain controversial. Here, we employed two newly generated Cypripedium chloroplast genomes with five other published genomes to elucidate their genomic characteristics. The two genomes were 162,773–207,142 bp in length and contained 128–130 genes, including 82–84 protein-coding genes, 38 tRNA genes, and 8 rRNA genes. We identified 2,192 simple sequence repeats, 786 large repeat sequences, and 7,929 variable loci. The increase of repeat sequences (simple sequence repeats and large repeat sequences) causes a significant amplification in the chloroplast genome size of Cypripedium. The expansion of the IR region led to the pseudogenization or loss of genes in the SSC region. In addition, we identified 12 highly polymorphic loci (Pi > 0.09) suitable for inferring the phylogeny of Cypripedium species. Based on data sets of whole chloroplast genomes (IRa excluded) and protein-coding sequences, a well-supported phylogenetic tree was reconstructed, strongly supporting the five subfamilies of Orchidaceae and the genus Cypripedium as monophyletic taxa. Our findings also supported that C. palangshanense belonged to sect. Palangshanensia rather than sect. Retinervia. This study also enriched the genomic resources of Cypripedium, which may help to promote the conservation efforts of these endangered species.

Plasmonic imaging technology can offer a novel way for nanofabrication, with the advantages of low-cost, high yield, and large area, having potentially promising applications in various nanostructures manufacturing. However, the previous studies mainly focus on the simulation and experimental research of fixed period or fixed structure size metasurface fabrication, which limits the range of its applications. In this paper, we proposed and analyzed the imaging characteristics of the reflective plasmonic structures, selected the best structure in the fabrication process by parameter analyses, and concluded that the air gap has the most significant influence on imaging quality of plasmonic imaging technology. Then we experimentally demonstrated its ability in fabricating multi-scale patterns. A 10mm × 16 mm large-scale structural color metasurface with periods from 414.3 to 580 nm has been designed and manufactured. Furthermore, the feasibility of fabricating metasurface whose radius varies from 75 to 150 nm is also verified under the same condition. The proposed method is expected to have widespread applications in multi-functional metasurface devices.

Abstract Radioresistance continues to be the leading cause of recurrence and metastasis in nasopharyngeal cancer. Long noncoding RNAs are emerging as regulators of DNA damage and radioresistance. LINC-PINT was originally identified as a tumor suppressor in various cancers. In this study, LINC-PINT was significantly downregulated in nasopharyngeal cancer tissues than in rhinitis tissues, and low LINC-PINT expressions showed poorer prognosis in patients who received radiotherapy. We further identified a functional role of LINC-PINT in inhibiting the malignant phenotypes and sensitizing cancer cells to irradiation in vitro and in vivo. Mechanistically, LINC-PINT was responsive to DNA damage, inhibiting DNA damage repair through ATM/ATR-Chk1/Chk2 signaling pathways. Moreover, LINC-PINT increased radiosensitivity by interacting with DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and negatively regulated the expression and recruitment of DNA-PKcs. Therefore, these findings collectively support the possibility that LINC-PINT serves as an attractive target to overcome radioresistance in NPC.

Abstract Background Early diagnostic indicators and the identification of possible progression to severe or critical COVID-19 in children are unknown. To investigate the immune characteristics of early SARS-CoV-2 infection in children and possible key prognostic factors for early identification of critical COVID-19, a retrospective study including 121 children with COVID-19 was conducted. Peripheral blood lymphocyte subset counts, T cell-derived cytokine concentrations, inflammatory factor concentrations, and routine blood counts were analyzed statistically at the initial presentation. Results The T lymphocyte subset and natural killer cell counts decreased with increasing disease severity. Group III (critical cases) had a higher Th/Tc ratio than groups I and II (common and severe cases); group I had a higher B cell count than groups II and III. IL-6, IL-10, IFN-γ, SAA, and procalcitonin levels increased with increasing disease severity. Hemoglobin concentration, and RBC and eosinophil counts decreased with increasing disease severity. Groups II and III had significantly lower lymphocyte counts than group I. T, Th, Tc, IL-6, IL-10, RBC, and hemoglobin had relatively high contribution and area under the curve values. Conclusions Decreased T, Th, Tc, RBC, hemoglobin and increased IL-6 and IL-10 in early SARS-CoV-2 infection in children are valuable indices for early diagnosis of severe disease. The significantly reduced Th and Tc cells and significantly increased IL-6, IL-10, ferritin, procalcitonin, and SAA at this stage in children with critical COVID-19 may be closely associated with the systemic cytokine storm caused by immune dysregulation.

Abstract Background Hepatocellular carcinoma (HCC), derived from hepatocytes, is the main histological subtype of primary liver cancer and poses a serious threat to human health due to the high incidence and poor prognosis. This study aimed to establish a multigene prognostic model to predict the prognosis of patients with HCC. Results Gene expression datasets (GSE121248, GSE40873, GSE62232) were used to identify differentially expressed genes (DEGs) between tumor and adjacent or normal tissues, and then hub genes were screened by protein–protein interaction (PPI) network and Cytoscape software. Seventeen genes among hub genes were significantly associated with prognosis and used to construct a prognostic model through COX hazard regression analysis. The predictive performance of this model was evaluated with TCGA data and was further validated with independent dataset GSE14520. Six genes (CDKN3, ZWINT, KIF20A, NUSAP1, HMMR, DLGAP5) were involved in the prognostic model, which separated HCC patients from TCGA dataset into high- and low-risk groups. Kaplan–Meier (KM) survival analysis and risk score analysis demonstrated that low-risk group represented a survival advantage. Univariate and multivariate regression analysis showed risk score could be an independent prognostic factor. The receiver operating characteristic (ROC) curve showed there was a better predictive power of the risk score than that of other clinical indicators. At last, the results from GSE14520 demonstrated the reliability of this prognostic model in some extent. Conclusion This prognostic model represented significance for prognosis of HCC, and the risk score according to this model may be a better prognostic factor than other traditional clinical indicators.

Diabetes mellitus (DM) increases the destruction of periodontal tissue and impairs osteogenesis differentiation. Exendin-4 (Ex-4), a glucagon-like peptide-1 (GLP-1) analogue, can be used for treating DM and promotes bone regeneration. The aim of this study was to explore the effect and mechanism of Ex-4 on improving the osteogenesis of periodontal ligament stem cells (PDLSCs) in a high glucose environment. Alkaline phosphatase staining and alizarin red staining were used to detect the osteogenic differentiation of PDLSCs. The results showed that 10 nM Ex-4 could reduce the osteogenesis inhibition of PDLSCs induced by high glucose. RT-PCR and western blot results showed that Ex-4 increased the osteogenesis-related gene expression of ALP, Runx2, and Osx, and upregulated the phosphorylation of P38, JNK, and ERK1/2; the peak effect was observed in the range 0.5–1.0 h. Mitogen-activated protein kinase (MAPK) inhibitors PD98059, SB203580, and SP600125 blocked the effects of Ex-4 on MAPK activation and decreased the expression of ALP, Runx2, and Osx in PDLSCs. Moreover, after Ex-4 treatment, the total β-catenin, p-GSK3β, LEF, and Runx2 protein levels increased under normal or high glucose environments. In conclusion, our results indicated that Ex-4 regulates the MAPK and WNT signaling pathways to alleviate the osteogenic inhibition of PDLSCs in a high glucose environment.

Gamma-aminobutyric acid (GABA) significantly affects plant responses to heavy metals in hydroponics or culture media, but its corresponding effects in plant–soil systems remain unknown. In this study, different GABA dosages (0–8 g kg−1) were added to the rhizosphere of Coreopsis grandiflora grown in Cd-contaminated soils. Cd accumulation in the shoots of C. grandiflora was enhanced by 38.9–159.5% by GABA in a dose-dependent approach because of accelerated Cd absorption and transport. The increase in exchangeable Cd transformed from Fe-Mn oxide and carbonate-bound Cd, which may be mainly driven by decreased soil pH rather than GABA itself, could be a determining factor responsible for this phenomenon. The N, P, and K availability was affected by multiple factors under GABA treatment, which may regulate Cd accommodation and accumulation in C. grandiflora. The rhizospheric environment dynamics remodeled the bacterial community composition, resulting in a decline in overall bacterial diversity and richness. However, several important plant growth-promoting rhizobacteria, especially Pseudomonas and Sphingomonas, were recruited under GABA treatment to assist Cd phytoextraction in C. grandiflora. This study reveals that GABA as a soil amendment remodels the rhizospheric environment (e.g., soil pH and rhizobacteria) to enhance Cd phytoextraction in plant–soil systems.

Abstract Background Despite the capability of emergency surgery to reduce the mortality of severe spontaneous intracranial hemorrhage (SSICH) patients, the effect and safety of surgical treatment for severe spontaneous intracranial hemorrhage (SSICH) patients receiving long-term oral antiplatelet treatment (LOAPT) remains unclear. In consideration of this, the cohort study is aimed at figuring out the effect and safety of emergency surgery for SSICH patients on LOAPT. Methods As a multicenter and prospective cohort study, it will be conducted across 7 representative clinical centers. Starting in September 2019, the observation is scheduled to be completed by December 2022, with a total of 450 SSICH patients recruited. The information on clinical, radiological, and laboratory practices will be recorded objectively. All of the patients will be monitored until death or 6 months after the occurrence of primary hemorrhage. Results In this study, two comparative cohorts and an observational cohort will be set up. The primary outcome is the effect of emergency surgery, which is subject to assessment using the total mortality and comparison in the survival rate of SSICH patients on LOAPT between surgical treatment and conservative treatment. The second outcome is the safety of surgery, with the postoperative hemorrhagic complication which is compared between the operated SSICH patients on and not on LOAPT. Based on the observation of the characteristics and outcome of SSICH patients on LOAPT, the ischemic events after discontinuing LOAPT will be further addressed, and the coagulation function assessment system for operated SSICH patients on LOAPT will be established. Conclusions In this study, we will investigate the effect and safety of emergency surgery for SSICH patients on LOAPT, which will provide an evidence for management in the future. Ethics and dissemination The research protocol and informed consent in this study were approved by the Institutional Review Board of Beijing Tiantan Hospital (KY2019-096-02). The results of this study are expected to be disseminated in peer-reviewed journals in 2023. Trial registration Name: Effect and safety of surgical intervention for severe spontaneous intracerebral hemorrhage patients on long-term oral antiplatelet treatment. ChiCTR1900024406 . Date of registration is July 10, 2019.