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ABSTRACTIntroductionKRAS is a critical oncogenic protein intricately involved in tumor progression, and the difficulty in targeting KRAS has led it to be classified as an ‘undruggable target.’ Among the various KRAS mutations, KRASG12Dis highly prevalent and represents a promising therapeutic target, yet there are currently no approved inhibitors for it.Area coveredThis review summarizes numerous patents and literature featuring inhibitors or degraders of KRASG12Dthrough searching relevant information in PubMed, SciFinder and Web of Science databases from 2021 to February 2024, providing an overview of the research progress on inhibiting KRASG12Din terms of design strategies, chemical structures, biological activities, and clinical advancements.Expert opinionSince the approval of AMG510(Sotorasib), there has been an increasing focus on the inhibition of KRASG12D, leading to numerous reports of related inhibitors and degraders. Among them, MRTX1133, as the first KRASG12Dinhibitor to enter clinical trials, has demonstrated excellent tumor suppression in various KRASG12D-bearing human tumor xenograft models. It is important to note, however, that understanding the mechanisms of acquired resistance caused by KRAS inhibition and developing additional combination therapies is crucial. Moreover, seeking covalent inhibition of KRASG12Dalso holds significant potential.

Ischemia-reperfusion injury (IRI) often stems from an imbalance between mitochondrial dynamics and autophagy. Melatonin mitigates IRI by regulating mitochondrial dynamics. However, the precise molecular mechanism underlying the role of melatonin in reducing IRI through modulating mitochondrial dynamics remains elusive. The objective of this study was to investigate whether pretreatment with melatonin before IRI confers protective effects by modulating mitochondrial dynamics and mitophagy. Melatonin pretreatment was administered to HK-2 cells and live rats before subjecting them to hypoxia-reoxygenation or IRI, respectively. Cells and rat kidney models were evaluated for markers of oxidative stress, autophagy, mitochondrial dynamics, and the expression of adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) and phospho-AMPKα (P-AMPK). After renal IRI, increased mitochondrial fission and autophagy were observed, accompanied by exacerbated cellular oxidative stress injury and aggravated mitochondrial dysfunction. Nevertheless, melatonin pretreatment inhibited mitochondrial fission, promoted mitochondrial fusion, and attenuated autophagy levels. This intervention was correlated with a notable reduction in oxidative stress injury and remarkable restoration of mitochondrial functionality. Ischemia-reperfusion injury led to a decline in P-AMPK levels, whereas melatonin pretreatment increased the level of P-AMPK levels. Silencing AMPK with small interfering RNA exacerbated mitochondrial damage, and in this context, melatonin pretreatment did not alleviate mitochondrial fission or autophagy levels but resulted in sustained oxidative stress damage. Collectively, these findings indicate that melatonin pretreatment shields the kidneys from IRI by mitigating excessive mitochondrial fission, moderating autophagy levels, and preserving appropriate mitochondrial fission, all in an AMPK-dependent manner.

The patch with a superlubricated surface shows great potential for the prevention of postoperative adhesion during soft tissue repair. However, the existing patches suffer from the destruction of topography during superlubrication coating and lack of pro-healing capability. Herein, we demonstrate a facile and versatile strategy to develop a Janus nanofibrous patch (J-NFP) with antiadhesion and reactive oxygen species (ROS) scavenging functions. Specifically, sequential electrospinning is performed with initiators and CeO2nanoparticles (CeNPs) embedded on the different sides, followed by subsurface-initiated atom transfer radical polymerization for grafting zwitterionic polymer brushes, introducing superlubricated skin on the surface of single nanofibers. The poly(sulfobetaine methacrylate) brush-grafted patch retains fibrous topography and shows a coefficient of friction of around 0.12, which is reduced by 77% compared with the pristine fibrous patch. Additionally, a significant reduction in protein, platelet, bacteria, and cell adhesion is observed. More importantly, the CeNPs-embedded patch enables ROS scavenging as well as inhibits pro-inflammatory cytokine secretion and promotes anti-inflammatory cytokine levels. Furthermore, the J-NFP can inhibit tissue adhesion and promote repair of both rat skin wounds and intrauterine injuries. The present strategy for developing the Janus patch exhibits enormous prospects for facilitating soft tissue repair.

According to the statistical results of the reciprocating compressor maintenance in chemical enterprises, the probability of faults caused by wear or damage of vulnerable parts inside the cylinder is close to 80%. Now, fault diagnosis of vulnerable parts inside the cylinder is relied on vibration signal, acoustic emission signal, or thermal parameters. However, it is difficult to extract eigenvalues from vibration signals and acoustic emission signals, which can be disturbed by noise easily. Thermal parameters are relatively stable and less affected by noise. The measurement of thermal parameters requires drilling testing holes through the cylinder wall, which will decrease the strength of the cylinder. According to the working principle of the compressor, fault of the vulnerable parts inside the cylinder would change the pressure and temperature distribution at the suction and the discharge port of the cylinder, while these state parameters are monitored by the parameter monitoring system on most of the compressors. For these reasons, a fault prediction model based on state parameters learning is proposed in this paper aiming to fault diagnosis of vulnerable parts inside the cylinder, which could make fault prediction without adding new hardware cost, such as sensors. Optimized back propagation neural network method by genetic algorithm (GA-BP) is applied to establish the fault prediction model to describe normal working process of the compressor. When fault of vulnerable parts inside the cylinder occurs, monitored pressure and temperature would deviate from the predicted value by the fault prediction. The degree of the deviation is adopted to the fault diagnosis. Then, experiments simulating the fault condition were carried out, and it shows that the accuracy of fault diagnosis using this method could exceed 95%. Verification test shows that the proposed method could successfully predict the fault before the unplanned shutdown.

Deployed in space orbits, solar cell arrays are subjected to daunting challenges posed by exceedingly harsh thermal environments. During their operational lifespan in space, potential failures at the joints between solar cells and interconnecting strips can adversely affect the longevity of solar cell arrays. To enhance the thermal reliability of solar cell joints in intricate space conditions, this study delved into the influence of thermal cycle on mechanical properties and microstructures of parallel gap resistance welding (PGRW) joints utilizing both silver (Ag) and Ag-plated Kovar foils. Operating at respective current densities of 410 A/mm2and 420 A/mm2, these two types of foils exhibit solid-phase interfaces characterized by elemental diffusion. Interface of the joint of Ag foil experiences microscopic deformation and accumulated strain during the thermal cycle, with cracks initiating and propagating at the edges of joint interface. With an escalation in the number of thermal cycles, tensile-shear performance deteriorates, and the fracture morphology shifts from a ductile fracture with evident dimples to a deformation-intensive fracture attributed to thermal fatigue, draped in Ag grains. Conversely, the joints of Ag-plated Kovar foil demonstrate minimal alterations in mechanical properties, microstructures, and fracture morphology due to thermal cycling. This phenomenon reflects noteworthy thermal reliability spanning from −160 °C to 120 °C. The investigation into PGRW joints of Ag-plated Kovar foil holds significant implications for satisfying the high-reliability of solar cell arrays in hostile space environments.

Multilabel electrocardiogram (ECG) classif- ication is of great significance for the diagnosis of cardiovascular diseases, and it is also a challenging task because of the various of pathological patterns across different cardiac abnormalities. This article analyzes the complex spatial-temporal variations information contained in the 12-lead ECG from a new perspective and proposes an advanced deep neural network (DNN) framework to accurately identify various multilabel ECG abnormalities. First, the 12-lead ECG was modeled as 3-D spatial-temporal variations involving the intraperiod and interperiod temporal dimensions and cross-lead spatial dimension. Then, a 3-D spatial-temporal learning network (3D-STLNet) was carefully designed to extract the complex pathological features from the 3-D spatial-temporal variations. Second, the multihead attention (MHA) mechanism was introduced into the proposed network to extract global temporal dependencies in ECG segments, which further improved the performance of the proposed network. By integrating a residual backbone network, a 3D-STLNet, and the MHA module, our proposed network allows end-to-end learning and prediction in a unified framework. The influence of several classic threshold selection strategies on the performance of multilabel ECG classification algorithm was also analyzed, which provides a reference for subsequent research on optimal threshold selection for multilabel ECG classification. Finally, our proposed network was evaluated on multiple large multilabel ECG public datasets, and the performance of our network outperforms that of current state-of-the-art networks, which demonstrates that our network has great competitiveness in identifying a wider range of multilabel ECG abnormalities.

Abstract: Wound dressing materials which are capable of meeting the demands of accelerating wound closure and promoting wound healing process have being highly desired. Electrospun nanofibrous materials show great application potentials for wound healing owing to relatively large surface area, better mimicry of native extracellular matrix, adjustable waterproofness and breathability, and programmable drug delivery process. In this review article, we begin with a discussion of wound healing process and current commercial wound dressing materials. Then, we emphasize on electrospun nanofibrous materials for wound dressing, covering the efforts for controlling fiber alignment and morphology, constructing 3D scaffolds, developing waterproof-breathable membrane, governing drug delivery performance, and regulating stem cell behavior. Finally, we finish with challenges and future prospects of electrospun nanofibrous materials for wound dressings. Graphic Abstract:

Simultaneously transmitting and reflecting reconfigurable intelligent surface (STAR-RIS) is emerging as a promising technology by achieving full-space coverage and further improving system performance. However, most existing works adopted an independent phase-shift model, which is high-cost and may be difficult to achieve in realistic wideband systems. Consequently, a coupled phase-shift STAR-RIS enhanced downlink multi-user multiple-input single-output orthogonal frequency division multiplexing system is investigated for both unicast and broadcast communications in this paper. We aim to maximize the average sum-rate (ASR) for all subcarriers by jointly optimizing the precoding matrices and the reflecting and transmitting coefficients (RTCs). Specifically, a block coordinate descent algorithm is proposed to iteratively design each block of a multiblock problem reformulated by the original one. The precoding matrices are optimized by the Lagrangian multiplier method for low computational complexity. For the RTCs, an element-based alternating optimization algorithm is proposed to optimize the coupled phase-shift and amplitude coefficients. Simulation results validate the effectiveness of the proposed algorithm by comparing the ASR with that of other benchmarks. Moreover, its performance closely approaches the upper bound under various practical user proportion scenarios on both sides of the STAR-RIS.

Socio-emotional interaction is considered a crucial factor that may affect the effectiveness and efficiency of collaborative argumentation and deserves further exploration. This study explored what temporal and sequential patterns of socio-emotional interaction could promote or hinder productive collaborative argumentation by comparing the differences between four high- and four low-performing groups. The 8 target groups were selected from a larger sample of 14 groups according to their scores of groups’ argument maps after participating in a 90-min collaborative argumentation activity. Using content analysis method, groups’ video recordings were coded and analyzed. The results indicated several differences between the high- and low-performing groups. First, more positive socio-emotional interactions were found in the high-performing groups while more negative socio-emotional interactions were discovered in the low-performing groups. Second, using smiles or laughter to express disagreement (P2) and interrupting others (N1) were more essential factors that may affect argumentation quality in the Chinese context. Third, temporal analysis suggested that in low-performing groups, the sharp rise in negative socio-emotional interactions may be provoked by more cognitive interactions in the initial phase that aimed to persuade opponents. Fourth, sequential analysis showed that repeated negative interactions in low-performing groups may lead to a negative atmosphere and thus, made the increasing tension less likely to be relieved by positive interactions. Whereas in high-performing groups, frequent transitions between positive socio-emotional interactions helped create a positive atmosphere, which could avoid conflict escalation and resolve the potential tension caused by negative interactions. Finally, pedagogical implications were suggested.

This brief proposes a dual-core quad-mode millimeter-wave (mm-wave) voltage-controlled oscillator (VCO) using a compact multi-mode LC network with a mode-independent switched transformer technique. On top of the dual-mode main LC tank, the mode-independent switched transformer technique introduces two additional oscillation modes, further extending the frequency tuning range with a small chip area overhead, while the mode-independent feature reduces the cost of switch off-capacitance compared with the conventional switched transformers. Implemented in 65nm CMOS process, the proposed VCO achieves a measured octave frequency tuning range from 20.65 to 40.55 GHz. The measured best phase noise is -131.04 dBc/Hz at 10 MHz offset from 20.65 GHz. The measured best figure-of-merit (FoM) is 187.25 dBc/Hz at 10 MHz offset from 26.66 GHz, corresponding to a figure-of-merit of tuning range and area (FoM textsubscript TA) of 216.72 dBc/Hz thanks to the proposed compact multi-mode LC network and the mode-independent switched transformer technique. The VCO consumes 9.75-to-18.85 mW from a 0.65 V supply voltage. The core area is 0.048 mm2.

Reliability of joints in solar arrays significantly influences the service life of satellites. Interface between solar cell and interconnector experiences serious temperature cycling during space service which would further lead to failure. To further improve the interface joining thermal reliability, elucidation of the interface formation and corresponding microstructure evolution during thermal fatigue is necessary. In this study, parallel gap resistance welded (PGRW) multi-layered joint between GaAs solar cell and Ag foil are subjected to different temperature cycling tests (−160–120 °C, −165–160 °C) with various cycles. Obtained results confirm the joining mechanism of the joint as solid-solution interdiffusion between Ag foil and Au surface of solar cell electrode. Also, conducted temperature cycling essentially lead to thermal fatigue process at Ag/Au interface, therefore more serious interface strength degradation is generated by larger temperature cycling range. Joint failure is initiated by thermal fatigue induced dislocation and residual strain concentrations around dissimilar interface. And the large mismatch in coefficients of thermal expansion (CTE) of the multilayer structure amplifies the thermal fatigue effect.

In this work, we harnessed the diffusiveness of the resistant states in 3-D resistive random access memory (RRAM) array and implemented a true random number generator (TRNG). The fluctuation of the resistance states serves as the random source, which is then amplified by peripheral ring oscillator (RO) circuits. The peripheral circuits are fabricated in a 55-nm CMOS process. Measurement results show that the TRNG supports a maximum throughput of 1 Gb/s and passes the NIST test across −40 °C to 125 °C. The RRAM cells enjoy good robustness under high temperature, as the baking experiment shows. The TRNG obviates the need for calibration circuits and requires no startup circuits. The proposed work harvests the fluctuation of analog resistance of RRAM cells, enriching the TRNG family aimed for Internet of Things (IoT) application.

We herein compared the diagnostic accuracy of the BI‐RADS, ABVS, SWE, and combined techniques for the classification of breast lesions. Breast lesions were appraised using the BI‐RADS classification system as well as the combinations of BI‐RADS plus ABVS (BI‐RADS + ABVS) and BI‐RADS plus SWE (BI‐RADS + SWE), and both methods (BI‐RADS + ABVS + SWE) by two specialties Medical Ultrasound physician. The Fisher's exact and χ2tests were performed to compare the degree of malignancy for the various methods with a pathology ground truth. Receiver operating characteristic curves (ROC) were generated and the corresponding area under the curve (AUC) values were determined to test the diagnostic efficacy of the various methods and identify the optimal SWE cut‐off indicative of malignancy. The incidence of the retraction phenomenon on ABVS images of the malignant group was significantly higher (P< .001) than that of the benign group. The specificity, sensitivity, and positive and negative predictive values of the BI‐RADS classification were 88.72, 79.38, 83.70, and 85.50%, respectively. BI‐RADS plus SWE‐Max exhibited enhanced specificity, sensitivity, and positive and negative predictive values of 88.72, 92.78, 85.70, and 94.40%, respectively. Similarly, when BI‐RADS + ABVS was utilized, the sensitivity and negative predictive value increased to 95.88 and 96.40%, respectively. BI‐RADS + ABVS + SWE possessed the highest overall sensitivity (96.91%), specificity (94.74%), and positive (93.10%) and negative (97.70%) predictive values from all four indices. ABVS and SWE can reduce the subjectivity of BI‐RADS. As a result, BI‐RADS + ABVS + SWE resulted in the best diagnostic accuracy.

Self-expanding cryogels hold unique prospects for treating uncontrollable hemorrhages. However, development of a mechanically robust, tissue-adhesive, and bioactive self-expanding cryogel enabling effective hemostasis and tissue repair has remained a great challenge. Herein, we report a superelastic cellular-structured bioactive glass nanofibrous cryogel (BGNC) composed of highly flexible BG nanofibers and citric acid-cross-linked poly(vinyl alcohol). These BGNCs exhibit high absorption capacity (3169%), fast self-expanding ability, near zero Poisson’s ratio, injectability, high compressive recovery at a strain of 80%, robust fatigue resistance (almost no plastic deformation after 800 cycles at a strain of 60%), and good adhesion with diverse tissues. The BGNCs provide sustained release of Ca, Si, and P ions. Moreover, the BGNCs present better blood clotting and blood cell adhesion ability and superior hemostatic capacity in rabbit liver and femoral artery hemorrhage models as compared with commercial gelatin hemostatic sponges. In addition, BGNCs are able to stop bleeding in rat cardiac puncture injury in about 1 min. Furthermore, the BGNCs are capable of promoting rat full-thickness skin wound healing. The development of self-expanding BGNCs with superelasticity and bioadhesion provides a promising strategy for exploring multifunctional hemostatic and wound repair materials.

To understand how malignant tumors develop, we tracked cell membrane, nuclear membrane, spindle, and cell cycle dynamics in polyploid giant cancer cells (PGCCs) during the formation of high-grade serous carcinoma organoids using long-term time-lapse imaging. Single cells underwent traditional mitosis to generate tissue with uniform nuclear size, while others formed PGCCs via asymmetric mitosis, endoreplication, multipolar endomitosis, nuclear fusion, and karyokinesis without cytokinesis. PGCCs underwent restitution multipolar endomitosis, nuclear fragmentation, and micronuclei formation to increase nuclear contents and heterogeneity. At the cellular level, the development of PGCCs was associated with forming transient intracellular cells, termed fecundity cells. The fecundity cells can be decellularized to facilitate nuclear fusion and synchronized with other nuclei for subsequent nuclear replication. PGCCs can undergo several rounds of entosis to form complex tissue structures, termed fecundity structures. The formation of PGCCs via multiple modes of nuclear replication in the absence of cytokinesis leads to an increase in the nuclear-to-cytoplasmic (N/C) ratio and intracellular cell reproduction, which is remarkably similar to the mode of nuclear division during pre-embryogenesis. Our data support that PGCCs may represent a central regulator in malignant histogenesis, intratumoral heterogeneity, immune escape, and macroevolution via the de-repression of suppressed pre-embryogenic program in somatic cells.

In situforming injectable hydrogels hold great potential for the treatment of irregular wounds. However, their practical applications were hindered by long gelation time, poor mechanical performance, and a lack of a natural extracellular matrix structure. Herein, amino-modified electrospun poly(lactic-co-glycolic acid) (APLGA) short fibers with uniform distribution were introduced into gelatin methacrylate/oxidized dextran (GM/ODex) hydrogels. In comparison with the fiber aggregation structure in the PLGA fiber-incorporated hydrogels, the hydrogels with APLGA fibers possessed a uniform porous structure. The highly dispersed APLGA short fibers accelerated the sol–gel phase transition of the hydrogel due to the formation of dynamic Schiff-base bonds between the fibers and hydrogels. Furthermore, in combination with UV-assisted crosslinking, a rapid gelation time of 90 s was achieved for the double-crosslinked hydrogels. The addition of APLGA short fibers as fillers and the formation of the double-crosslinking network enhanced the mechanical performance of the hydrogels. Furthermore, the fiber–hydrogel composites exhibited favorable injectability, excellent biocompatibility, and improved cell infiltration. In vivoassessment indicated that the GM/ODex-APLGA hydrogels successfully filled the full-thickness defects and improved wound healing. This work demonstrates a promising solution for the treatment of irregular wounds.

Recently, there has been a surge of interest in developing new types of photothermal materials driven by the ongoing demand for efficient energy conversion, environmental concerns, and the need for sustainable solutions. However, many existing photothermal materials face limitations such as high production costs or narrow absorption bands, hindering their widespread application. In response to these challenges, researchers have redirected their focus toward harnessing the untapped potential of organic waste-derived and bioderived materials. These materials, with photothermal properties derived from their intrinsic composition or transformative processes, offer a sustainable and cost-effective alternative. This review provides an extended categorization of organic waste-derived and bioderived materials based on their origin. Additionally, we investigate the mechanisms underlying the photothermal properties of these materials. Key findings highlight their high photothermal efficiency and versatility in applications such as water and energy harvesting, desalination, biomedical applications, deicing, waste treatment, and environmental remediation. Through their versatile utilization, they demonstrate immense potential in fostering sustainability and support the transition toward a greener and more resilient future. The authors’ perspective on the challenges and potentials of platforms based on these materials is also included, highlighting their immense potential for real-world implementation.

Bacterial biofilms on wounds can lead to ongoing inflammation and delayed reepithelialization, which brings a heavy burden to the medical systems. Nitric oxide based treatment has attracted attention because it is a promising strategy to eliminate biofilms and heal infected wounds. Herein, a series of tryptophan-based poly(ester urea)s with good biodegradation and biocompatibility were developed for the preparation of composite mats by electrospinning. Furthermore, the mats were grafted with a nitric oxide donor (nitrosoglutathione, GSNO) to provide one type of NO loading cargo. The mats were found to have a prolonged NO release profile for 408 h with a maximum release of 1.0 μmol/L, which had a significant effect on killing bacteria and destructing biofilms. The designed mats were demonstrated to promote the growth of cells, regulate inflammatory factors, and significantly improve collagen deposition in the wound, eventually accelerating wound-size reduction. Thus, the studies presented herein provide insights into the production of NO-releasing wound dressings and support the application of full-thickness wound healing.

Aligned fibrous hydrogels capable of recruiting endogenous neural stem/progenitor cells (NSPCs) show great promise in spinal cord injury (SCI) repair. However, the hydrogels suffer from severe issues in close contact with the transected nerve stumps and harnessing the NSPC fate in the lesion microenvironment. Herein, we report aligned collagen-fibrin (Col-FB) fibrous hydrogels with stretchable property, adhesive behavior, and stromal cell-derived factor-1α (SDF1α)/paclitaxel (PTX) spatiotemporal delivery capability. The resultant Col-FB fibrous hydrogels exhibited 1.98 times longer elongation at break (230%), 2.55 times lower Young’s modulus (17.93 ± 1.16 KPa), and 2.21 times greater adhesive strength (3.45 ± 0.48 KPa) than collagen (Col) fibrous hydrogels. The soft aligned fibrous hydrogels simulate the oriented microstructure and soft tissue feature of a natural spinal cord and provide elasticity and adhesivity to ensure a persistent close contact with host stumps. The repair of complete transection SCI in rats demonstrates that “middle-to-bilateral” SDF1α gradient release induced endogenous NSPC migration to the lesion site in 10 days, and SDF1α/PTX sequential release promoted neuronal differentiation of the recruited NSPCs over 8 weeks, leading to hind limb locomotion recovery. The presented strategy was proved to be efficient for harnessing endogenous NSPCs, which facilitate SCI repair significantly.

To meticulously establish an efficient photothermal multifunctional hydrogel dressing is a prospective strategy for the treatment of diabetic chronic wounds. Herein, glucose oxidase (GOx) was added to polydopamine/acrylamide (PDA/AM) hydrogels to reduce hyperglycemia to a normal level (3.9–6.1 mmol L−1) and enhance compressive properties (55 kPa) and adhesive properties (32.69 kPa), which are capable of hemostasis in the wound. Then, MnO2nanoparticles were encapsulated into a polydopamine/acrylamide (PDA/AM) hydrogel, endowing it with excellent antibacterial properties (E. coliand S. aureuswere 97.87% and 99.99%) under the irradiation of 808 nm NIR; meanwhile, the biofilm was eliminated completely. Besides, O2was generated (18 mg mL−1) by the decomposition of H2O2under the catalysis of MnO2, which could accelerate the formation of angiogenesis and promote the crawling and proliferation of cells. Furthermore, the diabetic wound in vivotreated with the PDA/AM/GOx/MnO2hydrogel had a less inflammatory response and faster healing speed, which was completely healed in 14 days. Therefore, the multifunctional hydrogels with the capability of high compressible, hemostasis, antibacterial, hyperglycemia manipulation, and O2generation, demonstrate promise in diabetic chronic wound dressing.

In-line terahertz pulsed imaging has been utilized to measure the film coating thickness of individual tablets during the coating process in a production-scale pan coater. A criteria-based waveform selection algorithm (WSA) was developed to select terahertz signals reflected from the surface of coating tablets and determine the coating thickness. Since the WSA uses many criteria thresholds to select terahertz waveforms of sufficiently high quality, it could reject some potential candidate tablet waveforms that are close but do not reach the threshold boundary. On the premise of the availability of large datasets, we aim to improve the efficiency of WSA with machine learning. This article presents a recurrent neural network approach to optimize waveform selection. In comparison with the conventional method of WSA, our approach allows more than double the number of waveforms to be selected while maintaining excellent agreement with offline thickness measurements. Moreover, the processing time of waveform selection decreases so that it can be applied for real-time coating monitoring in the pharmaceutical industry, which leads to more advancements in quality control for pharmaceutical film coating.

In traditional psychological counseling, limitations of patients’ subjective feelings and expressive abilities, as well as the varying levels of professional skills and conversation skills of counselors, make it difficult to properly solve psychological problems. Emotional recognition technology can help psychological counselors better understand the inner world of patients, thereby providing more targeted psychological counseling services for college students. 2D convolutional neural network-long short-term memory (2DCNN-LSTM) and 1D convolutional neural network-long short-term memory network (1DCNN-LSTM) were used for emotion recognition. Wavelet packet coefficient sequences were utilized to analyze multimodal data; multi-core convolutional neural network models were applied for multimodal feature layer fusion, and LSTM recurrent neural networks were used to effectively identify valence and college student emotions. The experimental results showed that under multimodal recognition, the average recognition accuracy of 2DCNN-LSTM for fourth-year university students was 18.7% higher than that of 1DCNN-LSTM for fourth-year university students. Compared with 1DCNN-LSTM, 2DCNN-LSTM can achieve better recognition accuracy. The research results can help psychological counselors better understand the emotional state and needs of students and provide more personalized and targeted counseling services.

The goal of this study was to explore the regulatory mechanisms of phenyllactic acid (PLA) overaccumulation in Lactobacillus plantarum. The dynamics of PLA production revealed that 24 h was a suitable fermentation time, at which one of the largest differences in PLA content between strains S1 and YM-4-3 was 22.42 mg/L. Additionally, an optimization experiment showed that PLA production under the optimal condition (sample YM-4-3y) was up to 400.74 mg/L, 7.61–13.26 times as those of YM-4-3 and S1. Subsequently, an integrated analysis of genomic, transcriptomic and metabolomic data revealed that, YM-4-3 and YM-4-3y, compared with S1, although lacking a complete de novo biosynthetic pathway, increased PLA production by strengthening the core pathway and central carbon metabolism, and weakening the biosynthesis pathway of amino acids and their derivatives. These changes can provide sufficient precursors and compensate for or balance the energy consumed by the reinforced core pathway.

Reduced-protein diet can save protein ingredients and reduce nitrogen (N) losses. However, the effect of low protein diet on the mineral uptake and utilization in broilers needs to be explored. The aim of this study was to investigate the effect of low-protein diet on the growth performance, N deposition, mineral contents in serum, tissues and excreta, and the activities and gene expression of related enzymes in tissues of medium-growing yellow-feathered broilers, so as to elucidate the relationship between dietary protein level and the absorption and utilization of minerals in broilers. A total of 72 1-d-old Spotted-Brown male broilers were randomly allotted to 1 of 2 treatments with 6 replicate cages of 6 birds per cage for each treatment. The dietary crude protein (CP) levels for the two treatments were 21% (the control treatment) and 19% (low protein treatment), respectively. The experimental period was 30 d. The results showed that no differences (P> 0.05) were detected in average daily gain, average daily feed intake and feed: gain ratio of broilers during 1 to 30 d between the two treatments. However, low protein intake increased (P< 0.05) N retention rate, serum P, Cu and Mn, and excreta Cu, Mn and Zn, and decreased (P< 0.05) liver P and excreta P. In addition, birds fed low protein diet had higher (P< 0.05) manganese superoxide dismutase, and total superoxide dismutase activities in liver, and total antioxidant capacity and malondialdehyde content in heart, and lower (P< 0.05) copper-zinc superoxide dismutase (CuZnSOD) and succinate dehydrogenase activities in liver and CuZnSOD mRNA level in heart. In conclusion, the reduction of dietary CP content from 21% to 19% improved N retention, the absorption of P, Cu and Mn, as well as the antioxidant ability of liver and heart, and influenced metabolic utilization of P, Cu, Zn, Fe and Mn in medium-growing yellow-feathered broilers from 1 to 30 d of age.

The fault of vulnerable parts in the cylinder accounts for a large proportion of the fault of the reciprocating compressor. In order to find the fault of the compressor in time, parameter monitoring is usually applied to give forewarning or warning of the compressor fault. Because the setting of forewarning value relies on experiences, over protection and delayed warning events often occur. Recently, the research of fault diagnosis methods combined with artificial intelligence technology is gradually rising. However, most of the fault diagnosis methods based on artificial intelligence technology rely on large number of fault data for fault learning. The problem is that it is almost impossible to obtain the sample data including all of the fault types. To solve above problems, a fault diagnosis method for reciprocating compressor based on the prediction of comprehensive index extracted from the expansion process in indicator diagram is proposed. In this method, a model predicting the comprehensive index of expansion process under normal working conditions is established. The expansion process will change significantly when faults occur, which could result in a deviation between the predicted value and the actual value of the comprehensive index. This deviation is utilized in this paper for fault diagnosis. Fault experiments are carried out to verify the effectiveness of the proposed method. An obvious advantage of this method is that no fault data is needed to establish the fault diagnosis model. It would relatively save the cost of the fault diagnosis and be conducive to application. The accuracy of this method for discriminating fault conditions of an individual vulnerable part is more than 94%. The combined fault conditions with multiple parts under fault state could also be successfully distinguished from normal conditions by this method.

The individual and combined inhibitory activities of propolis extract (PE) and Hermetia illucenslarval proteins (Black soldier fly larvae proteins) (BSFLP) against Aspergillus nigerwere investigated. The antifungal effects of PE, BSFLP and Synergy of PE and BSFLP (SPB) against Aspergillus nigerwere determined by mycelial growth, spore germination rate and hyphal elongation. Membrane integrity was measured by assessing changes in extracellular proteins, reducing sugars, and electrical conductivity. Intracellular MDA, H2O2, ergosterol, and mannan contents were also evaluated. SEM was used to observe the morphology of the Aspergillus nigermycelium. Additionally, AutoDock Tools software and multi-ligand docking methods were used to study the synergistic interactions of ligand combinations on the receptor. The results showed that the combination of PE and BSFLP had excellent effects. During the treatment of antifungal agents, the membrane permeability changed and a large amount of content leaked, while control check (CK) remained almost unchanged. Ergosterol content was found to increase, while mannan content decreased significantly, leading to cell death. In addition, SPB can cause abnormal accumulation of MDA and H2O2, leading to oxidative stress in cells. SEM results showed that morphology of Aspergillus nigertreated with SPB was severe wrinkling, distortion and even breakage. Multi-ligand docking results showed that the binding affinity of receptor 1KS5 to 14 complex ligands increased, as indicated by the decrease in docking energy values. These results provide scientific basis for further study on the application of SPB and development of effective antifungal products.

The stable protection of the walls of high-temperature geothermal wells is a challenging issue for sustainably exploiting geothermal resources. However, the cement stone filling layer of the cemented portion of the well deteriorates gradually during geothermal mining due to the dry-wet cycles of the saline geothermal water, reducing the service life of the geothermal well. For this, this paper presented five groups of cement stone cylinders with salt contents of 0%, 1%, 6%, and 11%, which were subjected to heating to 300 °C and 1–5 dry-wet cycles. Nuclear magnetic resonance (NMR) and nonmetallic detection were used to test and analyze the porosity and wave velocity. Additionally, the damage evolution induced by dry-wet cycles was captured based on acoustic emission (AE) data. The experimental results indicated that the heating process primarily resulted in mineral and salt crystal expansion, which in turn caused damage. The damage threshold due to the salt content was found to be 6%. The sudden increase in the thermal stress caused by cooling and deterioration of the tensile strength of the cement column were the key factors in the damage during the cooling process. As the number of cycles increased, the accumulated AE energy moved forward and backward, with decreasing and increasing temperature, respectively. The threshold of signal mutation in the heating process is 200 °C, and the accumulated AE energy decreases by 11.7%. When the salt content was 0%, 1%, 6% and 11%, the wave velocity decreased by 19%, 27.3%, 35.5% and 35.9%, respectively. This study also proposed a damage model, which could provide theoretical support for long-term health monitoring and safety protection of geothermal wells.

It has been a major challenge to treat osteoporotic bone defects with irregular shapes. Although bioactive glass offers an attractive material for bone regeneration, its inherent brittleness has greatly limited its scope of application. Herein, we report the fabrication of bioactive glass (SiO2–CaO) nanofibers with excellent flexibility to even allow for 180° bending. The bioactive glass nanofibers could be further assembled into 3D fibrous scaffolds with chitosan serving as the linkers. The scaffolds constructed from an assembly of 85SiO2–15CaO nanofibers and chitosan (85SiO2–15CaO NF/CS) possessed significantly better mechanical properties when benchmarked against both 75SiO2–25CaO nanofiber- and chitosan-based scaffolds. Moreover, the 85SiO2–15CaO NF/CS scaffolds exhibited an elastic behavior, with full recovery from 80% compression and good fatigue resistance over 1000 cycles of compression under water. Upon implantation, the elastic fibrous scaffolds were able to deform and fit irregularly shaped bone defects, followed by a self-deploying behavior to achieve a perfect match with the cavities. When applied to the repair of an osteoporotic calvarial defect in a rat model, the 85SiO2–15CaO NF/CS scaffolds showed substantial promotion of bone regrowth and vascularization. This new class of 3D fibrous scaffold provides a promising advancement in engineering smart materials for complex bone repair.

Nowadays, manipulation of quad-rotors faces complexity in controller parameter tuning process and system instability under uncertainties. Internal model control is featured with less controller parameters, simpler tuning process than conventional methods, good robustness and perfect capability in rejection of uncertainties. All its merits can be applied in the field of nano-quad-rotor control since its internal model is easy to be obtained and the suffered uncertainties, especially persistent ones such as model uncertainties and winds, can be rejected by the algorithm effectively. In this paper, an internal model control cascade Proportion-Integration-Differentiation (PID) method is developed to enhance the robustness and improve the capability of uncertainty rejection of nano-quad-rotors flying under persistent uncertainties. The system can be stabilized in a very easy way with all controller parameters tuned within 0 to 1. Comparison with internal model control method was carried out numerically; the results show that, in dealing with persistent uncertainties, the internal model control cascade PID-based method presents significant superiority in the maintenance of both the accuracy of trajectory tracking and the stability of attitude.

ABSTRACTThe evolution of Chinese environmental policy and politics can be better understood in the broader context of institutional changes that have taken place since the late 1970s. In this study, an analytical framework was established to analyze how overall institutional changes were reflected in the roles of relationships between governmental and non-governmental actors engaged in environmental governance. Institutional changes were observed at three levels: informal institutions (cultural traditions, and political ideology); formal institutions (the polity, political system, property rights, and judiciary); and governing mechanisms (structures, regulatory approaches, and incentives). This analysis of interactions between institutional changes and the changing environmental process explained not only the drives and constraints behind China’s environmental policy evolution so far but also shed light on future challenges and opportunities.

Injury-activated endogenous neural stem cells (NSCs) in the spinal cord have promising therapeutic applications for rebuilding the neuronal relays after spinal cord injury (SCI) because of their lack of immune-rejection following exogenous cell transplantation. However, these NSCs rarely differentiate into neurons and the damaged axonal regenerative ability is drastically reduced due to the adverse SCI microenvironment. Cetuximab, an EGFR signaling antagonist, has demonstrated the ability of promoting NSC differentiation into neurons. Taxol, in addition to stabilizing microtubules, has shown potential for enhancing axonal regeneration and reducing scar formation after SCI. In this study, we further verified the combined therapeutic effects of Cetuximab and Taxol on inhibition of scar deposition and promotion of neuronal differentiation, axonal outgrowth and functional recovery in a rat severe SCI model. A linear orderly collagen scaffold modified with Cetuximab and Taxol was grafted into the SCI site after the complete removal of 4 mm of spinal tissue. The results showed that the combined functional scaffold implantation significantly increased neural regeneration to reconnect the neural network. Moreover, scaffold transplantation decreases the deposition of varied scar-related inhibitors within the lesion center, further reflecting the need for a combination dedicated to increasing motor function following SCI. Collagen scaffold based-combined therapy provides a potential strategy for improving functional restoration of the injured spinal cord.

TiO2-based heterojunction fibrous membranes with stable hierarchical nanostructures, excellent visible-light-driven photocatalytic activity, and easy-recycling ability would hold great promise in environmental remediation; however, it still remains a great challenge to construct such fantastic fibrous membranes. Herein, soft and hierarchical heterostructured BiOBr-anchored TiO2nanofibrous membranes (BiOBr@TiO2NFM) were fabricated by the sol–gel electrospinning technique combined with a facile successive ionic layer adsorption and reaction (SILAR) process. The well-crystallized BiOBr nanoplates with lamellar structure were uniformly grown onto TiO2nanofibers, and the size and amount of BiOBr nanostructures could be finely regulated through rationally adjusting the growth cycles of SILAR. Benefiting from the large surface area, enhanced visible-light response, and intimately connected interfacial heterojunctions, the resultant membranes exhibited superior photocatalytic performance for rhodamine B (RhB) degradation under visible light irradiation, including a high degradation efficiency of 95.5% within 120 min and excellent reusability in 5 cycles. More importantly, the membranes still maintained good mechanical flexibility and structural integrity after utilization and could be directly extracted from solution. This study may provide a new strategy for the design and fabrication of soft hierarchical nanostructured TiO2-based fibrous membranes for environmental remediation and other potential applications.

Shield tunnels are inevitably damaged by complex diseases during operation, so repair and reinforcement are essential. The stainless steel corrugated plate (SSCP) has many advantages for tunnel structure reinforcement because of its high strength, lightweight, convenient construction and installation, and corrosion resistance. Mechanical behaviors of an unreinforced segmental joint and a segmental joint reinforced with a new SSCP were investigated by full-scale tests. The reinforcement test took into account the actual reinforcement conditions in the field, i.e.the joint bore the load alone before reinforcement, maintained the load during reinforcement, and bore the load together with the SSCP after reinforcement. The experimental results demonstrate that: (1) both unreinforced and reinforced joints exhibit a compressive-flexural failure mechanism, and their failure is manifested by concrete crushing in the compressed zone of the joint. (2) Compared to that unreinforced joint, the bending moment and ultimate vertical load of the reinforced one are increased by 73.7% and 119.3%, respectively. And the reinforced joint is stiffer than the unreinforced one, reflecting that SSCP reinforcement enables higher stiffness. (3) Trends of strain-moment curves of the bent bolts and concrete are similar in the unreinforced and reinforced joints. Under the same load, the strains in the reinforced group are smaller than those in the unreinforced group, indicating that the SSCP in the reinforced group shares the load. (4) The strains of the SSCP exhibits a symmetrical distribution in the length direction with the joint section as the symmetrical plane. The strains at the trough show tensile strain, while the strains at the crest show compressive strain. The combined force of the corrugated steel plate cross-section is tensile (i.e., SSCP shares the tension load in the tensile zone of the joint), reflecting the reinforcement effect of SSCP.

Electrospun bioactive glass fibers show great potential as scaffolds for bone tissue engineering due to their architectural biomimicry of the bone extracellular matrix and their composition capable of providing soluble bioactive cues for bone regeneration and remodeling. Trace elements can be doped to further promote osteogenesis and angiogenesis during bone regeneration. Cationic substitution of strontium for calcium in bioactive glass positively enhances osteoblast phenotype, while suppressing osteoclast activity. Further, the addition of copper spontaneously improves the vascularization during neobone formation. The objective of this study was to fabricate and characterize electrospun bioactive glass fibers doped with strontium and copper and evaluate their potential for bone repair/regeneration in vitro. Different ratios of strontium and copper were doped in electrospun bioactive glass fibers. The released strontium and copper from doped fibers could reach effective concentrations within 40 h and last for 4 weeks. These bioactive glass fibers demonstrate their bioactivity by promoting osteoblastic and endothelial cell activity and inhibiting the formation of osteoclasts or bone resorbing cells. Additionally, in vitro cell culture of different cell types in the presence of extraction solutions of the electrospun bioactive glass fibers showed that the dopants achieved their individual goals without causing significant cytotoxicity. Altogether, this novel class of bioactive glass fibers holds great promise for bone regeneration.

PAX8 is the most commonly used immunomarker to link a carcinoma to the gynecologic tract; however, it lacks specificity. Through mining The Cancer Genome Atlas mRNA expression profile data, we identified SOX17 as a potential specific marker at the mRNA level for gynecologic tumors. To evaluate the utility of this marker in the identification of the gynecologic origin of a given carcinoma, we performed immunochemical staining in a large cohort of ovarian and endometrial cancer cases (n = 416), together with a large cohort of solid tumors from other organs (n = 1544) in tissue microarrays. Similar to PAX8, SOX17 was highly expressed in different subtypes of ovarian carcinoma (97.5% for SOX17 vs 97% for PAX8 in serous carcinoma, 90% vs 90% in endometrioid carcinoma, and 100% vs 100% in clear cell carcinoma), except for mucinous carcinoma (0% vs 27%), and was also highly expressed in different subtypes of endometrial carcinoma (88% vs 84% in endometrioid carcinoma, 100% vs 100% in serous and clear cell carcinoma). SOX17 was not expressed in thyroid and renal cell carcinomas, whereas PAX8 expression was high (86% and 85%, respectively). In addition, SOX17 was expressed at low levels in cervical adenocarcinoma (20%) and had no expression in cervical squamous carcinoma, mesothelioma, and carcinomas from the breast, lung, pancreas, colon, stomach, liver, bladder, and salivary gland. Our data indicate that SOX17 is not only a sensitive but also a specific marker for the origin of ovarian and endometrial carcinomas.

The vasculature influences the progression and resolution of tissue inflammation. Capillaries express vascular endothelial growth factor (VEGF) receptors, including neuropilins (NRPs), which regulate interstitial fluid flow. NRP2, a receptor of VEGFA and semaphorin (SEMA) 3F ligands, is expressed in the vascular and lymphatic endothelia. Previous studies have demonstrated that blocking VEGF receptor 2 attenuates VEGFA-induced vascular permeability. The inhibition of NRP2 was hypothesized to decrease vascular permeability as well. Unexpectedly, massive tissue swelling and edema were observed in Nrp2−/−mice compared with wild-type littermates after delayed-type hypersensitivity reactions. Vascular permeability was twofold greater in inflamed blood vessels in Nrp2-deficient mice compared to those in Nrp2-intact littermates. The addition of exogenous SEMA3F protein inhibited vascular permeability in Balb/cJ mice, suggesting that the loss of endogenous Sema3F activity in the Nrp2-deficient mice was responsible for the enhanced vessel leakage. Functional lymphatic capillaries are necessary for draining excess fluid after inflammation; however, Nrp2-mutant mice lacked superficial lymphatic capillaries, leading to 2.5-fold greater fluid retention and severe lymphedema after inflammation. In conclusion, Nrp2 deficiency increased blood vessel permeability and decreased lymphatic vessel drainage during inflammation, highlighting the importance of the NRP2/SEMA3F pathway in the modulation of tissue swelling and resolution of postinflammatory edema.

The reconstruction of bone usually depends on substitute transplantation, which has drawbacks including the limited bone substitutes available, comorbidity, immune rejection, and limited endogenous bone regeneration. Here, we constructed a functionalized bone substitute by combining application of the demineralized bone matrix (DBM) and collagen-binding stromal-cell-derived factor-1α (CBD-SDF-1α). DBM was a poriferous and biodegradable bone substitute, derived from bovine bone and consisting mainly of collagen. CBD-SDF-1α could bind to collagen and be controllably released from the DBM to mobilize stem cells. In a rat femur defect model, CBD-SDF-1α-modified DBM scaffolds could efficiently mobilize CD34+and c-kit+endogenous stem cells homing to the injured site at 3 days after implantation. According to the data from micro-CT, CBD-SDF-1α-modified DBM scaffolds could help the bone defects rejoin with mineralization accumulated and bone volume expanded. Interestingly, osteoprotegerin (OPG) and osteopontin (OPN) were highly expressed in CBD-SDF-1α group at an early time after implantation, while osteocalcin (OCN) was more expanded. H&E and Masson’s trichrome staining showed that the CBD-SDF-1α-modified DBM scaffold group had more osteoblasts and that the bone defect rejoined earlier. The ultimate strength of the regenerated bone was investigated by three-point bending, showing that the CBD-SDF-1α group had superior strength. In conclusion, CBD-SDF-1α-modified DBM scaffolds could promote bone regeneration by recruiting endogenous stem cells.

One of the most fascinating areas in the field of smart biopolymers is biomolecule sensing. Accordingly, multifunctional biomimetic, biocompatible, and stimuli-responsive materials based on hydrogels have attracted much interest. Within this framework, the design of nanostructured materials that do not require any external energy source is beneficial for developing a platform for sensing glucose in body fluids. In this article, we report the realization and application of an innovative platform consisting of two outer layers of a nanocomposite plasmonic hydrogel plus one inner layer of electrospun mat fabricated by electrospinning, where the outer layers exploit photoinitiated free radical polymerization, obtaining a compact and stable device. Inspired by the exceptional features of chameleon skin, plasmonic silver nanocubes are embedded into a poly(N-isopropylacrylamide)-based hydrogel network to obtain enhanced thermoresponsive and antibacterial properties. The introduction of an electrospun mat creates a compatible environment for the homogeneous hydrogel coating while imparting excellent mechanical and structural properties to the final system. Chemical, morphological, and optical characterizations were performed to investigate the structure of the layers and the multifunctional platform. The synergetic effect of the nanostructured system’s photothermal responsivity and antibacterial properties was evaluated. The sensing features associated with the optical properties of silver nanocubes revealed that the proposed multifunctional system is a promising candidate for glucose-sensing applications.

Compared to the nerve guidance conduits (NGCs) constructed from a single layer of aligned nanofibers, bilayer NGCs with random and aligned nanofibers in the outer and inner layers are more robust and tear-resistant during surgical procedures thanks to an isotropic mechanical property provided by the random nanofibers. However, it remains unclear whether the random nanofibers will interfere with the aligned nanofibers to alter the extension pattern of the neurites and impede regeneration. To answer this question, we seeded dorsal root ganglia (DRG) on a double-layered scaffold, with aligned and random nanofibers on the top and bottom layers, respectively, and evaluated the outgrowth of neurites. The random nanofibers in the bottom layer exerted a negative impact on the extension of neurites projecting from the DRG, giving neurites a less ordered structure compared to those cultured on a single layer of aligned nanofibers. The negative impact of the random nanofibers could be effectively mitigated by preseeding the double-layered scaffold with Schwann cells. DRG cultured on top of such a scaffold exhibited a neurite outgrowth pattern similar to that for DRG cultured on a single layer of aligned nanofibers. We further fabricated bilayer NGCs from the double-layered scaffolds and tested their ability to facilitate nerve regeneration in a rat sciatic nerve injury model. Both histomorphometric analysis and functional characterization demonstrated that bilayer NGCs with an inner surface that was preseeded with Schwann cells could reach 54%, 64.2%, and 74.9% of the performance of isografts in terms of nerve fiber number, maximum isometric tetanic force, and mass of the extensor digitorum longus muscle, respectively. It can be concluded that the bilayer NGCs hold great potential in facilitating motor axon regeneration and functional motor recovery.

A new method for generating both continuous and discrete density gradients in microparticles of biodegradable polymers via an electrospray technique is reported. The gradients are generated by spatially varying the deposition time of electrosprayed microparticles. The substrate coated with a density gradient of microparticles has varying surface roughness, offering a unique system for studying the effect of physical cues on neurite outgrowth from dorsal root ganglia.An optimal surface roughness for promoting neuron adhesion and neurite extension in vitro is obtained. Furthermore, this capability of approach is extended to generate a gradient of fluorescein isothiocyanate labeled bovine serum albumin by encapsulating it in the polymer microparticles in situ during electrospray. Taken together, this new class of substrates with gradients of microparticle density can potentially be used in various biomedical applications such as neural tissue engineering.

Here, a new approach is introduced to prepare large single crystals of π‐conjugated organic molecules from solution. Utilizing the concept of azeotropism, single crystals of tri‐isopropylsilylethynyl pentacene (TIPS‐PEN) with dimensions up to millimeters are facilely self‐assembled from homogeneous solutions comprising two solvents with opposing polarities and a positive azeotropic point. At solvent compositions close to the azeotropic point, an abrupt transition of morphology from polycrystalline thin‐films to large single crystals is found. How to adjust the initial ratio of the binary solvents so that the change in solvent composition during evaporation favors the specific H‐aggregation and promotes an efficient self‐assembly of TIPS‐PEN is explained. The charge‐carrier (hole) mobilities are substantially enhanced by a factor of 4 from the morphology of thin‐films to large single crystals used as active layer in field‐effect transistors. Additionally, this approach is extended to other π–π stacked organic molecules to elucidate its broad applicability.

Conductive core–sheath nanofibers are prepared by a combination of electrospinning and aqueous polymerization. Specifically, nanofibers electrospun from poly(ε‐caprolactone) (PCL) and poly(L‐lactide) (PLA) are employed as templates to generate uniform sheaths of polypyrrole (PPy) by in‐situ polymerization. These conductive core–sheath nanofibers offer a unique system to study the synergistic effect of different cues on neurite outgrowth in vitro. It is found that explanted dorsal root ganglia (DRG) adhere well to the conductive core–sheath nanofibers and generate neurites across the surface when there is a nerve growth factor in the medium. Furthermore, the neurites can be oriented along one direction and enhanced by 82% in terms of maximum length when uniaxially aligned conductive core–sheath nanofibers are compared with their random counterparts. Electrical stimulation, when applied through the mats of conductive core–sheath nanofibers, is found to further increase the maximum length of neurites for random and aligned samples by 83% and 47%, respectively, relative to the controls without electrical stimulation. Together these results suggest the potential use of the conductive core–sheath nanofibers as scaffolds in applications such as neural tissue engineering.

Electrospun nanofibers can be readily assembled into various types of scaffolds for applications in neural tissue engineering. The objective of this study is to examine and understand the unique patterns of neurite outgrowth from primary dorsal root ganglia (DRG) cultured on scaffolds of electrospun nanofibers having different orders, structures, and surface properties. We found that the neurites extended radially outward from the DRG main body without specific directionality when cultured on a nonwoven mat of randomly oriented nanofibers. In contrast, the neurites preferentially extended along the long axis of fiber when cultured on a parallel array of aligned nanofibers. When seeded at the border between regions of aligned and random nanofibers, the same DRG simultaneously expressed aligned and random neurite fields in response to the underlying nanofibers. When cultured on a double-layered scaffold where the nanofibers in each layer were aligned along a different direction, the neurites were found to be dependent on the fiber density in both layers. This biaxial pattern clearly demonstrates that neurite outgrowth can be influenced by nanofibers in different layers of a scaffold, rather than the topmost layer only. Taken together, these results will provide valuable information pertaining to the design of nanofiber scaffolds for neuroregenerative applications, as well as the effects of topology on neurite outgrowth, growth cone guidance, and axonal regeneration.

Electrospinning has been exploited for almost one century to process polymers and related materials into nanofibers with controllable compositions, diameters, porosities, and porous structures for a variety of applications. Owing to its high porosity and large surface area, a non‐woven mat of electrospun nanofibers can serve as an ideal scaffold to mimic the extracellular matrix for cell attachment and nutrient transportation. The nanofiber itself can also be functionalized through encapsulation or attachment of bioactive species such as extracellular matrix proteins, enzymes, and growth factors. In addition, the nanofibers can be further assembled into a variety of arrays or architectures by manipulating their alignment, stacking, or folding. All these attributes make electrospinning a powerful tool for generating nanostructured materials for a range of biomedical applications that include controlled release, drug delivery, and tissue engineering.

High temperature (HT) is one of the most important environmental stress factors and seriously threatens plant growth, development, and production. VQ motif-containing proteins are transcriptional regulators that have been reported to regulate plant growth and developmental processes, including responses to biotic and abiotic stresses. However, the relationships between VQ motif-containing proteins and HT stress have not been studied in depth in plants. In this study, transgenic apple (Malus domestica) plants overexpressing the apple VQ motif-containing protein-coding gene (MdVQ37) were exposed to HT stress, and the transgenic lines exhibited a heat-sensitive phenotype. In addition, physiological and biochemical studies revealed that, compared with WT plants, transgenic lines had lower enzymatic activity and photosynthetic capacity and lower amounts of nonenzymatic antioxidant system metabolites under HT stress. Transcriptome analysis revealed 1379 genes whose expression differed between the transgenic lines and WT plants. GO and KEGG pathway analyses showed that transcription factor activity and plant hormone signaling pathways were differentially influenced and enriched in the transgenic lines. Salicylic acid (SA) content analysis indicated that overexpression of MdVQ37reduced the content of endogenous SA by regulating the expression of SA catabolism-related genes, which ultimately resulted in disruption of the SA-dependent signaling pathway under HT stress. The application of SA slightly increased the survival rate of the transgenic lines under HT stress. Taken together, our results indicate that apple MdVQ37 has a regulatory function in basal thermotolerance by modulating the activity of transcription factors and SA homeostasis. Overall, this study provides novel insights that improve our understanding of the various functions of VQ motif-containing proteins.

Despite recent progress in hydrogel wound dressings, joint wound treatment remains an ongoing challenge due to their poor adhesive and stretchable properties. Herein, inspired by protein secretion-curing process of natural marine mussels, an adhesive nanofibrous hydrogel is developed via a sequential crosslinking strategy. Firstly, to avoid uncontrolled self-polymerization of dopamine (DA), DA grafted gelatin (GT) nanofibers are fabricated via electrospinning under pH value around 4. Further, the fibrous hydrogels are in-situ crosslinked under pH value of about 8 to strengthen the intermolecular interaction within fibers. The DA crosslinked GT fibrous hydrogels via Michael addition and Schiff base reaction exhibit superior adhesive and tensile properties which are 1.5 times and 3.1 times higher than those of GT fibrous hydrogels, respectively. The in vitrocytocompatibility tests and in vivowound healing study further prove that GT grafted DA nanofibrous hydrogels are able to accelerate wound healing. Taken together, we demonstrate a simple and versatile strategy for generating adhesive and stretchable nanofibrous hydrogel, showing a great potential for joint wound care.

Wound environment-responsive materials show great potential in skin repair. Herein, a temperature-responsive fibrous hydrogel was developed with the aid of the phase-change material of natural fatty acids. The extracellular matrix-like methacrylate gelatin (GelMA) nanofibrous hydrogels were fabricated via electrospinning and UV-crosslinking, followed by a depot of fatty acids/aspirin (ASP) encapsulated polydopamine (PDA). The as-prepared fibrous hydrogels showed a significantly faster ASP release at 40 °C compared with those of 25 °C and 37 °C, and an “on-off” drug release was achieved at heating and cooling cycles between 40 °C and 25 °C. The in vitrocell culture tests and in vivowound healing study proved that GelMA-PDA-ASP nanofibrous hydrogels facilitated the cell growth and accelerated wound repair. Taken together, the thermosensitive drug-releasing nanofibrous hydrogel, showed a great potential for wound care.

Background: The aim of this study was to evaluate the value of combining pelvic lymph node and tumor characteristics on positron emission tomography-intravoxel incoherent motion magnetic resonance (PET-IVIM MR) imaging for predicting lymph node metastasis in patients with cervical cancer, especially in those with negative lymph nodes on PET. Methods: The medical records of 95 patients with cervical cancer who underwent surgical resection with pelvic lymph node dissection were evaluated. The patients were divided into negative and positive groups according to postoperative pathologic lymph node diagnosis, and comparisons of the PET and IVIM-derived parameters between the two groups were performed. Univariate and multivariate analyses were performed to construct a predictive model of lymph node metastasis. Results: For all patients, tumor SUVmax, TLG, Dmin, PET and MRI for lymph node diagnosis showed significant differences between patients with and without confirmed lymph node metastasis. Univariate and multivariate logistic analysis showed that the combination of tumor TLG, Dminand PET for lymph node diagnosis had the strongest predictive value (AUC 0.913, p&lt; 0.001). For patients with PET-negative lymph nodes, SUVmax, SUVmean, MTV, TLG, and Dminshowed significant between-group differences, and univariate and multivariate logistic analysis showed that TLG had the strongest predictive value. Conclusions: The combination of tumorTLG, Dminand PET for lymph node diagnosis is a powerful prognostic factor for all patients. TLG has the best predictive performance in patients with PET negative lymph nodes.