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Abstract Targeted alpha (α) therapy (TAT) is an emerging therapeutic strategy for cancer treatment. To evaluate the safety and efficacy of targeted α‐therapy, the biodistribution and internal radiation dose of α‐emitting radionuclides should be determined. In vivo imaging of these radionuclides often involves the detection of gamma rays, X‐rays, and positrons generated during their complex decay processes. This review aims to classify the α‐emitting radionuclides (astatine‐211, actinium‐225, radium‐223, bismuth‐212, bismuth‐213, thorium‐227, and terbium‐149) according to their imageable signals. Additionally, this study summarizes various imaging modalities, including gamma camera imaging, single‐photon emission computed tomography, positron emission tomography, Compton imaging, bremsstrahlung imaging, and Cerenkov luminescence imaging, which hold potential for imaging α‐emitting radionuclides, to explore their biomedical applications in qualitative nuclide tracing and diagnosis, quantifying pharmacokinetics, and assessing prognosis and response to therapy.

Abstract Background Currently, the synthesis pathway of metal nuclide-labeled radiopharmaceuticals is mainly divided into two steps: first, connecting the chelator with the target molecule, and second, labeling the metal nuclide to the chelator. However, the second step of the reaction to label the metal nuclide requires high temperature (90–100 °C), which tends to denature and inactivate the target molecule, leading to loss of biological activities, especially the targeting ability. A feasible solution may be the click chemistry labeling method, which consists of reacting a metal nuclide with a chelating agent to generate an intermediate and then synthesizing a radiopharmaceutical agent via the click chemistry intermediate and the target molecule-alkyne compound. In this study, through the click chemistry of 177Lu-DOTA-N3 with prostate-specific membrane antigen (PSMA)-alkyne compound, 177Lu-labeled PSMA-targeted molecular probe was synthesized and evaluated for its potential to be cleared from the bloodstream and rapidly distributed to tissues and organs, achieving a high target/non-target ratio. 177Lu-PSMA-617 was utilized as an analogue for comparison in terms of synthesizing efficiency and PSMA-targeting ability. Results A novel 177Lu-labeled PSMA radioligand was successfully synthesized through the click chemistry of 177Lu-DOTA-N3 with PSMA-alkyne compound, and abbreviated as 177Lu-DOTA-CC-PSMA, achieving a radiochemical yield of 77.07% ± 0.03% (n = 6) and a radiochemical purity of 97.62% ± 1.49% (n = 6) when purified by SepPak C18 column. Notably, 177Lu-DOTA-CC-PSMA was characterized as a hydrophilic compound that exhibited stability at room temperature and commendable pharmacokinetic properties, such as the superior uptake (19.75 ± 3.02%ID/g at 0.5 h) and retention (9.14 ± 3.16%ID/g at 24 h) within xenografts of 22Rv1 tumor-bearing mice. SPECT/CT imaging indicated that radioactivity in both kidneys and bladder was essentially eliminated after 24 h, while 177Lu-DOTA-CC-PSMA was further enriched and retained in PSMA-expressing tumors, resulting in the high target/non-target ratio. Conclusion This study demonstrated the potential of click chemistry to unify the synthesis of metal radiopharmaceuticals, and 177Lu-DOTA-CC-PSMA was found for rapid clearance and appropriate chemical stability as a PSMA-targeted radioligand.

Background: Hepatocellular carcinoma (HCC) is among the most prevalent digestive system malignancies and is associated with a poor prognosis. Necroptosis, a form of regulated death mediated by death receptors, exhibits characteristics of both necrosis and apoptosis. Long non-coding RNAs (lncRNAs) have been identified as crucial regulators in tumor necroptosis. This study aims to identify the necroptosis-related lncRNAs (np-lncRNA) in HCC and investigate their relationships with prognosis. Method: The RNA-sequencing data, along with clinicopathological and survival information of HCC patients were sourced from The Cancer Genome Atlas (TCGA) database. The np-lncRNAs were analyzed to assess their potential in predicting HCC prognosis. Prognostic signatures related to necroptosis were constructed using stepwise multivariate Cox regression analysis. The prognosis of patients was compared using Kaplan-Meier (KM) analysis. The accuracy of the prognostic signature was evaluated using Receiver operating characteristic (ROC) analysis and decision curve analysis (DCA). Quantitative real-time polymerase chain reaction(qPCR) was employed to validate the lncRNAs expression levels of lncRNAs among samples from an independent cohort. Results: The np-lncRNAs ZFPM2-AS1, AC099850.3, BACE1-AS, KDM4A-AS1 and MKLN1-AS were identified as potential prognostic biomarkers. The prognostic signature constructed from these np-lncRNAs achieved an Area Under the Curve (AUC) of 0.773. Based on the risk score derived from the signature, patients were divided into two groups, with the high-risk group exhibiting poorer overall survival. Gene Set Enrichment Analysis (GSEA) revealed significantly different between the low risk and high risk groups in tumor-related pathways (such as mTOR, MAPK and p53 signaling pathways) and immune-related functions (like T cell receptor signaling pathway and natural killer cell mediated cytotoxicity). The increased expression of np-lncRNAs was confirmed in another independent HCC cohort. Conclusions: This signature offers a dependable method for forecasting the prognosis of HCC patients. Our findings indicate a subset of np-lncRNA biomarkers that could be utilized for prognosis prediction and personalized treatment strategies of HCC patients.

Abstract Despite the array of mammalian transgene switches available for regulating therapeutic protein expression in response to small molecules or physical stimuli, issues remain, including cytotoxicity of chemical inducers and limited biocompatibility of physical cues. This study introduces gene switches driven by short peptides comprising eight or fewer amino acid residues. Utilizing a competence regulator (ComR) and sigma factor X‐inducing peptide (XIP) from Streptococcus vestibularis as the receptor and inducer, respectively, this study develops two strategies for a peptide‐activated transgene control system. The first strategy involves fusing ComR with a transactivation domain and utilizes ComR‐dependent synthetic promoters to drive expression of the gene‐of‐interest, activated by XIP, thereby confirming its membrane penetrability and intracellular functionality. The second strategy features an orthogonal synthetic receptor exposing ComR extracellularly (ComREXTRA), greatly increasing sensitivity with exceptional responsiveness to short peptides. In a proof‐of‐concept study, peptides are administered to type‐1 diabetic mice with microencapsulated engineered human cells expressing ComREXTRA for control of insulin expression, restoring normoglycemia. It is envisioned that this system will encourage the development of short peptide drugs and promote the introduction of non‐toxic, orthogonal, and highly biocompatible personalized biopharmaceuticals for gene‐ and cell‐based therapies.

BackgroundHypoparathyroidism is the most common complication for patients who undergo total thyroidectomy (TT) with bilateral central lymph node dissection (BCLND). The objective of this retrospective study was to investigate the relationship between parathyroid autotransplantation (PA) and postoperative hypoparathyroidism.Materials and MethodsFour hundred and sixty-five patients with papillary thyroid carcinoma (PTC) who underwent TT with BCLND (including prophylactic and therapeutic BCLND) by the same surgeon were enrolled in this retrospective study. They were divided into five groups based on the number of PAs. Group 0 was defined as no PA, while Group 1, 2, 3, and 4 were considered as 1, 2, 3, and 4 PAs during TT with BCLND, respectively.ResultsTransient and permanent hypoparathyroidism occurred in 83 (17.8%) and 2 (0.4%) patients who underwent TT and BCLND, respectively. The incidence of transient hypoparathyroidism increased gradually with an increase in the number of PAs. Compared with the previous group, Groups 2 and 3 had significantly more cases of transient hypoparathyroidism (p=0.03 and p=0.04, respectively). All cases of permanent hypoparathyroidism occurred in the patients without PA. Compared with Group 0, there were more removed central lymph nodes (RCLNs) in patients with one PA. Furthermore, Group 2 had more metastatic central lymph nodes(MCLNs) and RCLNs than Group 1.The number of PAs was the only identified risk factor for transient hypoparathyroidism after the multivariate logistic regression analysis. The median parathyroid hormone level recovered to the normal range within 1 month after surgery.ConclusionWith an increasing number of PAs, the possibility of transient hypoparathyroidism also increases in patients with PTC who undergo TT and BCLND. Considering the rapid recovery of transient hypoparathyroidism in 1 month, two PAs during TT and BCLND could be a good choice, leading to an increase in the central lymph node yield and no permanent hypoparathyroidism. However, this conclusion should be validated in future multicenter prospective studies.

Abstract China, as a significant global consumer of chemical fertilizers and a leading producer of rice, faces challenges associated with low fertilizer efficiency and fewer utilization options of rice husks. The development of rice husk biochar‐based fertilizers (RHBF) offers a strategic solution to address these issues. In this study, diverse biochar fertilizer production techniques were used to develop four types of fertilizers: blended RHBF, soaked RHBF, high‐pressure soaked RHBF, and pure rice husk biochar coated fertilizer. The nutrients slow‐releasing performance of these four RHBF were compared by hydrostatic and soil column intermittent leaching methods. Effects of their application on rice growth, yield, and cadmium reduction potential were analyzed and compared by the pot trial. Results demonstrated that nutrients of the four RHBF were generally released slower in the soil compared with the conventional compound fertilizer (CK). The slow nutrient release effect was more pronounced under high‐pressure soaked RHBF. Notably, in the soil column leaching experiment, the cumulative leaching rates of nitrogen and K2O for RHBF3 (12.0% and 13.9%) were greatly lower than those of CK (42.3% and 51.3%). Moreover, the application of RHBF induced a marked enhancement in the nutrient use efficiency, grain yield, harvest index, and photosynthetic characteristics compared to CK. The average agronomic efficiency of P2O5 for the four RHBF increased by 102.8% compared with CK, while the average grain yield of the four RHBF increased by 20.6%. In addition, RHBF showed a significant reduction in Cd mobilization by an average of 80.1% compared to CK. This study offers a promising model for enhancing the comprehensive performance of RHBF and optimizing traditional fertilizer application practices.

Abstract Synthetic biology aims to engineer transgene switches for precise therapeutic protein control in cell‐based gene therapies. However, off‐the‐shelf trigger‐inducible gene circuits are usually switched on by single or structurally similar molecules. This study presents a mammalian gene‐switch platform that controls therapeutic gene expression by a wide range of molecules generating low, non‐toxic levels of reactive oxygen species (ROS). In this system, KEAP1 (Kelch‐like ECH‐associated protein 1) serves as ROS sensor, regulating the translocation of NRF2 (nuclear factor erythroid 2‐related factor 2) to the nucleus, where NRF2 binds to antioxidant response elements (ARE) to activate the expression of a gene of interest. It is found that a promoter containing eight‐tandem ARE repeats is highly sensitive to the low ROS levels generated by the soluble and volatile molecules, which include food preservatives, food additives, pharmaceuticals, and signal transduction inducers. In a proof‐of‐concept study, it is shown that many of these compounds can independently trigger microencapsulated engineered cells to produce sufficient insulin to restore normoglycemia in experimental type‐1 diabetic mice. It is believed that this system greatly extends the variety of small‐molecule inducers available to drive therapeutic gene switches.

Abstract Viral proteases and clinically safe inhibitors were employed to build integrated compact regulators of protein activity (iCROP) for post-translational regulation of functional proteins by tunable proteolytic activity. In the absence of inhibitor, the co-localized/fused protease cleaves a target peptide sequence introduced in an exposed loop of the protein of interest, irreversibly fragmenting the protein structure and destroying its functionality. We selected three proteases and demonstrated the versatility of the iCROP framework by validating it to regulate the functional activity of ten different proteins. iCROP switches can be delivered either as mRNA or DNA, and provide rapid actuation kinetics with large induction ratios, while remaining strongly suppressed in the off state without inhibitor. iCROPs for effectors of the NF-κB and NFAT signaling pathways were assembled and confirmed to enable precise activation/inhibition of downstream events in response to protease inhibitors. In lipopolysaccharide-treated mice, iCROP-sr-IκBα suppressed cytokine release (“cytokine storm”) by rescuing the activity of IκBα, which suppresses NF-κB signaling. We also constructed compact inducible CRISPR-(d)Cas9 variants and showed that iCROP-Cas9-mediated knockout of the PCSK9 gene in the liver lowered blood LDL-cholesterol levels in mice. iCROP-based protein switches will facilitate protein-level regulation in basic research and translational applications.

Reusable launch vehicles need to face complex and diverse environments during flight. The design of rocket recovery control law based on traditional deep reinforcement learning (DRL) makes it difficult to obtain a set of network architectures that can adapt to multiple scenarios and multi-parameter uncertainties, and the performance of deep reinforcement learning algorithm depends on manual trial and error of hyperparameters. To solve this problem, this paper proposes a self-learning control method for launch vehicle recovery based on neural architecture search (NAS), which decouples deep network structure search and reinforcement learning hyperparameter optimization. First, using network architecture search technology based on a multi-objective hybrid particle swarm optimization algorithm, the proximal policy optimization algorithm of deep network architecture is automatically designed, and the search space is lightweight design in the process. Secondly, in order to further improve the landing accuracy of the launch vehicle, the Bayesian optimization (BO) method is used to automatically optimize the hyperparameters of reinforcement learning, and the control law of the landing phase in the recovery process of the launch vehicle is obtained through training. Finally, the algorithm is transplanted to the rocket intelligent learning embedded platform for comparative testing to verify its online deployment capability. The simulation results show that the proposed method can satisfy the landing accuracy of the launch vehicle recovery mission, and the control effect is basically the same as the landing accuracy of the trained rocket model under the untrained condition of model parameter deviation and wind field interference, which verifies the generalization of the proposed method.

During aerial combat, when an aircraft is facing an infrared air-to-air missile strike, infrared baiting technology is an important means of penetration, and the strategy of effective delivery of infrared bait is critical. To address this issue, this study proposes an improved deep deterministic policy gradient (DDPG) algorithm-based intelligent bait-dropping control method. Firstly, by modeling the relative motion between aircraft, bait, and incoming missiles, the Markov decision process of aircraft-bait-missile infrared effect was constructed with visual distance and line of sight angle as states. Then, the DDPG algorithm was improved by means of pre-training and classification sampling. Significantly, the infrared bait-dropping decision network was trained through interaction with the environment and iterative learning, which led to the development of the bait-dropping strategy. Finally, the corresponding environment was transferred to the Nvidia Jetson TX2 embedded platform for comparative testing. The simulation results showed that the convergence speed of this method was 46.3% faster than the traditional DDPG algorithm. More importantly, it was able to generate an effective bait-throwing strategy, enabling the aircraft to successfully evade the attack of the incoming missile. The strategy instruction generation time is only about 2.5 ms, giving it the ability to make online decisions.

Marginal lands, such as those with saline soils, have potential as alternative resources for cultivating dedicated biomass crops used in the production of renewable energy and chemicals. Optimum utilization of marginal lands can not only alleviate the competition for arable land use with primary food crops, but also contribute to bioenergy products and soil improvement. Miscanthus sacchariflorus and M. lutarioriparius are prominent perennial plants suitable for sustainable bioenergy production in saline soils. However, their responses to salt stress remain largely unexplored. In this study, we utilized 318 genotypes of M. sacchariflorus and M. lutarioriparius to assess their salt tolerance levels under 150 mM NaCl using 14 traits, and subsequently established a mini-core elite collection for salt tolerance. Our results revealed substantial variation in salt tolerance among the evaluated genotypes. Salt-tolerant genotypes exhibited significantly lower Na+ content, and K+ content was positively correlated with Na+ content. Interestingly, a few genotypes with higher Na+ levels in shoots showed improved shoot growth characteristics. This observation suggests that M. sacchariflorus and M. lutarioriparius adapt to salt stress by regulating ion homeostasis, primarily through enhanced K+ uptake, shoot Na+ exclusion, and Na+ sequestration in shoot vacuoles. To evaluate salt tolerance comprehensively, we developed an assessment value (D value) based on the membership function values of the 14 traits. We identified three highly salt-tolerant, 50 salt-tolerant, 127 moderately salt-tolerant, 117 salt-sensitive, and 21 highly salt-sensitive genotypes at the seedling stage by employing the D value. A mathematical evaluation model for salt tolerance was established for M. sacchariflorus and M. lutarioriparius at the seedling stage. Notably, the mini-core collection containing 64 genotypes developed using the Core Hunter algorithm effectively represented the overall variability of the entire collection. This mini-core collection serves as a valuable gene pool for future in-depth investigations of salt tolerance mechanisms in Miscanthus.

Using contaminated land to grow lignocellulosic crops can deliver biomass and, in the long term, improve soil quality. Biostimulants and microorganisms are nowadays an innovative approach to define appropriate phytomanagement strategies to promote plant growth and metal uptake. This study evaluated biostimulants and mycorrhizae application on biomass production and phytoextraction potential of four lignocellulosic crops grown under two metal-contaminated soils. Two greenhouse pot trials were setup to evaluate two annual species (sorghum, hemp) in Italy and two perennial ones (miscanthus, switchgrass) in China, under mycorrhizae (M), root (B2) and foliar (B1) biostimulants treatments, based on humic substances and protein hydrolysates, respectively, applied both alone and in combination (MB1, MB2). MB2 increased the shoot dry weight (DW) yield in hemp (1.9 times more), sorghum (3.6 times more) and miscanthus (tripled) with additional positive effects on sorghum and miscanthus Zn and Cd accumulation, respectively, but no effects on hemp metal accumulation. No treatment promoted switchgrass shoot DW, but M enhanced Cd and Cr shoot concentrations (+84%, 1.6 times more, respectively) and the phytoextraction efficiency. Root biostimulants and mycorrhizae were demonstrated to be more efficient inputs than foliar biostimulants to enhance plant development and productivity in order to design effective phytomanagement strategies in metal-contaminated soil.

The pretreatment of lignocellulosic biomass such as Miscanthus grown on marginal agricultural land is very challenging and requires severe conditions to fractionate cell wall polymers for further valorization. The current study aimed to determine organic acid-based mild conditions to pretreat contrasting lignocellulosic Miscanthus genotypes for the efficient fractionation of cell wall components, with special focus on hemicellulose extraction. In doing so, five Miscanthus genotypes were subjected to four different acid treatments (sulfuric acid, oxalic acid, malonic acid, and citric acid) in a vertical high-pressure steam sterilizer. The results demonstrated that, among the organic acids, oxalic acid was identified as the most effective pretreatment solvent for hemicellulose separation, whereas citric acid yielded the highest amount of galacturonic acid, varying from 15 to 17 mg mL−1 across genotypes. One best performing genotype was selected for the enzymatic hydrolysis. Overall, M. floridulus genotypes exhibited the optimal quality traits for efficient bioconversion with second best in terms of ethanol production potential.

The identification of slag inclusion defects in welds is of the utmost importance in guaranteeing the integrity, safety, and prolonged service life of welded structures. Most research focuses on different kinds of weld defects, but branch research on categories of slag inclusion material is limited and critical for safeguarding the quality of engineering and the well-being of personnel. To address this issue, we design a simulated method using ultrasonic testing to identify the inclusion of material categories in austenitic stainless steel. It is based on a simulated experiment in a water environment, and six categories of cubic specimens, including four metallic and two non-metallic materials, are selected to simulate the slag materials of the inclusion defects. Variational mode decomposition optimized by particle swarm optimization is employed for ultrasonic signals denoising. Moreover, the phase spectrum of the denoised signal is utilized to extract the phase characteristic of the echo signal from the water–slag specimen interface. The experimental results show that our method has the characteristics of appropriate decomposition and good denoising performance. Compared with famous signal denoising algorithms, the proposed method extracted the lowest number of intrinsic mode functions from the echo signal with the highest signal-to-noise ratio and lowest normalized cross-correlation among all of the comparative algorithms in signal denoising of weld slag inclusion defects. Finally, the phase spectrum can ascertain whether the slag inclusion is a thicker or thinner medium compared with the weld base material based on the half-wave loss existing or not in the echo signal phase.

Miscanthus spp. has been regarded as a promising industrial plant for the sustainable production of bio-based materials. To assess its potential for microcrystalline cellulose (MCC) and cellulose nanocrystals (CNCs) production, 50 representative clones of M. sinensis and M. floridulus were selected from a nationwide collection showcasing the extensive diversity of germplasm resources. Descriptive analysis indicates that the dry biomass weight of M. floridulus is advantageous whereas M. sinensis demonstrates higher MCC and CNCs yields as well as a smaller CNCs particle size. Correlation analyses indicated that MCC yield is solely influenced by the cellulose content whereas the yield of CNCs is affected by both the cellulose content and CrI. Comparative analyses of the chemical composition, physical features (degree of polymerization, crystalline index, particle size distribution and zeta potential), and scanning electron microscopy indicated that the MCC and CNCs extracted from M. sinensis and M. floridulus exhibited remarkable stability and quality. Additionally, the CNCs derived from M. sinensis and M. floridulus exhibited a distinctive ball-shaped structure. Notably, machine learning has demonstrated its efficacy and effectiveness in the high-throughput screening of large populations of Miscanthus spp. for predicting the yield of MCC and CNCs. Our results have also laid the theoretical foundation for the exploration, cultivation, and genetic breeding of M. sinensis and M. floridulus germplasm resources with the purpose of MCC and CNCs preparation.

Abstract Objective Postoperative bile leakage (POBL) is one of the most common complications after liver resection. However, current studies on the risk factors for POBL and their impacts on surgical outcomes need to be more consistent. This study aims to conduct a meta‐analysis to analyze the risk factors for POBL after hepatectomy. Methods We incorporated all eligible studies from Embase, PubMed, and the Web of Science database (until July 2022) into this study. RevMan and STATA software were used to analyze the extracted data. Results A total of 39 studies, including 43,824 patients, were included in this meta‐analysis. We found that gender, partial hepatectomy, repeat of hepatectomy, extended hepatectomy, abdominal drain, diabetes, Child≥B, solitary tumor, and chemotherapy are the factors of grade B and C POBL. Some recognized risk factors were considered potential risk factors for grade B and C bile leakage because no subgroup analysis was performed, like HCC, cholangiocarcinoma, major resection, posterior sectionectomy, bi‐segmentectomy, S4 involved, S8 involved, central hepatectomy, and bile duct resection/reconstruction. Meanwhile, cirrhosis, benign diseases, left hepatectomy, and Segment 1 resection were not significant for grade B and C bile leakage. The influence of lateral sectionectomy, anterior sectionectomy, S1 involved, S3 involved, high‐risk procedure, laparoscope, and blood loss>1000 mL on POBL of ISGLS needs further research. Meanwhile, POBL significantly influenced overall survival (OS) after liver resection. Conclusions We identified several risk factors for POBL after hepatectomy, which could prompt the clinician to decrease POBL rates and make more beneficial decisions for patients who underwent the hepatectomy.

PurposeThe purpose of this study was to develop and validate a nomogram for estimating the risk of distant metastases (DM) in the early postoperative phase of medullary thyroid cancer (MTC).Patients and methodsWe retrospectively reviewed cases of patients diagnosed with MTC from the Surveillance, Epidemiology, and End Results (SEER) database from 2007 to 2017. In addition, we gathered data on patients who diagnosed as MTC at Department of Thyroid Surgery in the First Hospital of Jilin University between 2009 and 2021. Four machine learning algorithms were used for modeling, including random forest classifier (RFC), gradient boosting decision tree (GBDT), logistic regression (LR), and support vector machine (SVM). The optimal model was selected based on accuracy, recall, specificity, receiver operating characteristic curve (ROC), and area under curve (AUC). After that, the Hosmer-Lemeshow goodness-of-fit test, the brier score (BS) and calibration curve were used for validation of the best model, which allowed us to measure the discrepancy between the projected value and the actual value.ResultsThrough feature selection, we finally clarified that the following four features are associated with distant metastases of MTC, which are age, surgery, primary tumor (T) and nodes (N). The AUC values of the four models in the internal test set were as follows: random forest: 0.8786 (95% CI, 0.8070-0.9503), GBDT: 0.8402 (95% CI, 0.7606-0.9199), logistic regression: 0.8670(95%CI,0.7927-0.9413), and SVM: 0.8673 (95% CI, 0.7931-0.9415). As can be shown, there was no statistically significant difference in their AUC values. The highest AUC value of the four models were chosen as the best model since. The model was evaluated on the internal test set, and the accuracy was 0.84, recall was 0.76, and specificity was 0.87. The ROC curve was drawn, and the AUC was 0.8786 (95% CI, 0.8070-0.9503), which was higher than the other three models. The model was visualized using the nomogram and its net benefit was shown in both the Decision Curve Analysis (DCA) and Clinical Impact Curve (CIC).ConclusionProposed model had good discrimination ability and could preliminarily screen high-risk patients for DM in the early postoperative period.

Tumor radioresistance remains a key clinical challenge. The Hedgehog (HH) signaling pathway and glioma-associated oncogene (GLI) are aberrantly activated in several cancers and are thought to contribute to cancer radioresistance by influencing DNA repair, reactive oxygen species production, apoptosis, autophagy, cancer stem cells, the cell cycle, and the tumor microenvironment. GLI is reported to activate the main DNA repair pathways, to interact with cell cycle regulators like Cyclin D and Cyclin E, to inhibit apoptosis via the activation of B-cell lymphoma-2, Forkhead Box M1, and the MYC proto-oncogene, to upregulate cell stemness related genes (Nanog, POU class 5 homeobox 1, SRY-box transcription factor 2, and the BMI1 proto-oncogene), and to promote cancer stem cell transformation. The inactivation of Patched, the receptor of HH, prevents caspase-mediated apoptosis. This causes some cancer cells to survive while others become cancer stem cells, resulting in cancer recurrence. Combination treatment using HH inhibitors (including GLI inhibitors) and conventional therapies may enhance treatment efficacy. However, the clinical use of HH signaling inhibitors is associated with toxic side effects and drug resistance. Nevertheless, selective HH agonists, which may relieve the adverse effects of inhibitors, have been developed in mouse models. Combination therapy with other pathway inhibitors or immunotherapy may effectively overcome resistance to HH inhibitors. A comprehensive cancer radiotherapy with HH or GLI inhibitor is more likely to enhance cancer treatment efficacy while further studies are still needed to overcome its adverse effects and drug resistance.

BackgroundBecause the diameter of the suspicious lymph nodes is less than 1 cm and adjacent to important structures in the neck, the diagnosis of small LLNM is important but difficult without the help of fine needle aspiration (FNA). There are no relevant reports of risk factors that predict the risk of suspicious 0.05). Chi squared trend analysis showed that the increase in the number of risk factors gradually increased the malignancy possibility of suspicious

Abstract Determining the effect of perennial energy crop (PEC) cultivation on soil organic carbon (SOC) in marginal land soil is vital for carbon neutrality and bioeconomy development. However, a comprehensive and systematic evaluation of the response of SOC content to different PECs and its underlying drivers is still lacking. We used soil data collected from infertile red topsoil (0–20 cm) after 10 years of cultivation with Miscanthus (MS), Panicum virgatum (SG), and Saccharum arundinaceum (SA) to explore the changes in SOC stock induced by PEC. The roles of physical, chemical, and microbiological factors driving the increase in the SOC stock were investigated. Results revealed that SA and MS enhanced SOC stock by 87.97% and 27.52% relative to the uncultivated control. Conversely, PEC increased the percentage of soil mega‐aggregates, geometric mean diameters, soil chelate iron (Fe), and aluminum (Al) oxides, and reduced soil acidity for the infertile red soils. In addition, fungal richness and diversity for PEC soils were enhanced compared to the unplanted soil. It is possible that PEC cultivation reduced the relative abundance of copiotrophic fungi but increased the relative abundance of oligotrophic fungi. Furthermore, variance partitioning analysis revealed that chemical and microbiological factors accounted for 80.54% of the total variation for the SOC stock. The partial least squares path model showed that PEC cultivation enhanced soil carbon (C) stock via soil deacidification and increased soil bacterial function. In conclusion, this study confirms the SOC sequestration potential of PEC cultivation in marginal land and the underlying mechanism driving SOC stock. The main positive factors controlling soil C sequestration included “pH,” while the negative factors were “bacterial community,” “fungal community,” and “bacterial function.” Our research may help encourage and support decision‐makers of wasted marginal land conversion to PEC cultivation.

ObjectiveActive surveillance (AS) has been recommended as the first-line treatment strategy for low-risk (LR) papillary thyroid microcarcinoma (PTMC) according to the guidelines. However, preoperative imaging and fine-needle aspiration could not rule out a small group of patients with aggressive PTMC with large-volume lymph node micro-metastasis, extrathryoidal invasion to surrounding soft tissue, or high-grade malignancy from the AS candidates.MethodsAmong 2,809 PTMC patients, 2,473 patients were enrolled in this study according to the inclusion criteria. Backward stepwise multivariate logistic regression analysis was used to filter clinical characteristics and ultrasound features to identify independent predictors of high-risk (HR) patients. A nomogram was developed and validated according to selected risk factors for the identification of an HR subgroup among “LR” PTMC patients before operation.ResultsFor identifying independent risk factors, multivariable logistic regression analysis was performed using the backward stepwise method and revealed that male sex [3.91 (2.58–5.92)], older age [0.94 (0.92–0.96)], largest tumor diameter [26.7 (10.57–69.22)], bilaterality [1.44 (1.01–2.3)], and multifocality [1.14 (1.01–2.26)] were independent predictors of the HR group. Based on these independent risk factors, a nomogram model was developed for predicting the probability of HR. The C index was 0.806 (95% CI, 0.765–0.847), which indicated satisfactory accuracy of the nomogram in predicting the probability of HR.ConclusionTaken together, we developed and validated a nomogram model to predict HR of PTMC, which could be useful for patient counseling and facilitating treatment-related decision-making.

Abstract The ongoing COVID-19 pandemic has demonstrated that viral diseases represent an enormous public health and economic threat to mankind and that individuals with compromised immune systems are at greater risk of complications and death from viral diseases. The development of broad-spectrum antivirals is an important part of pandemic preparedness. Here, we have engineer a series of designer cells which we term autonomous, intelligent, virus-inducible immune-like (ALICE) cells as sense-and-destroy antiviral system. After developing a destabilized STING-based sensor to detect viruses from seven different genera, we have used a synthetic signal transduction system to link viral detection to the expression of multiple antiviral effector molecules, including antiviral cytokines, a CRISPR-Cas9 module for viral degradation and the secretion of a neutralizing antibody. We perform a proof-of-concept study using multiple iterations of our ALICE system in vitro, followed by in vivo functionality testing in mice. We show that dual output ALICESaCas9+Ab system delivered by an AAV-vector inhibited viral infection in herpetic simplex keratitis (HSK) mouse model. Our work demonstrates that viral detection and antiviral countermeasures can be paired for intelligent sense-and-destroy applications as a flexible and innovative method against virus infection.

Background: Gastric cancer (GC) progression is related with gene regulations. Objectives: This study explored underlying regulatory axis of circRNA PVT1 (circPVT1) in GC. Methods: GC cell lines were detected for circPVT1 expression with the normal mucous epithelial cell GES-1 as control. After regulation of circPVT1, miR-423-5p and SMAD3 expression through transfection, CCK8 evaluated the cell viability, Transwell measured the migratory and invasive capability of cells. Luciferase verified the paired bindings between miR-423-5p and CircPVT1 or SMAD3. The functions of CircPVT1/miR-423-5p/SMAD3 were evaluated using RT-PCR, CCK8, Transwell assays. Western blot analyzed EMT-related proteins and phosphorylation of Smad3 in GC cells. Immunofluorescence method was used to evaluate the EMT-related proteins as well. Results: CircPVT1 displayed higher expression in GC cells and knockdown led to decrease in cell growth, invasion and migration. CircPVT1 was targeted by miR-423-5p as a ceRNA of SMAD3. miR-423-5p upregulation suppressed both cicRNA PVT1 and SMAD3 in GC cells. Decrease in SMAD3 expression suppressed CircPVT1 by releasing miR-423-5p in cells, inhibiting cell growth, invasion and migration and suppressing the EMT process. Conclusion: CircPVT1 modulated cell growth, invasion and migration through EMT mediation in gastric cancer through miR-423-5p/Smad3 pathway.

Artificial receptors targeted to the secretory pathway often fail to exhibit the expected activity due to post-translational modifications and/or improper folding. Here, the authors engineer diverse synthetic receptors that reside in the cytoplasm, inside the endoplasmic reticulum, or on the plasma membrane through orientation adjustment of the receptor parts and by elimination of dysfunctional PTMs sites.

Abstract Marginal land conversion to perennial energy crops can provide biomass feedstocks and climate change mitigation. However, the effect of perennial energy crop cultivation on soil organic carbon (SOC) sequestration and its underlying mechanism in marginal land still remains incomplete. Here, SOC turnover, stability, and its potential sequestration were evaluated based on 10 years of land use change from C3 grass‐dominated marginal land to C4 energy crops Miscanthus and switchgrass cultivation. The naturally occurring 13C signature down to 60 cm depth was used to determine the energy crops‐derived C. Compared to reference marginal land, Miscanthus plantation increased the SOC stock at 0–60 cm depth by 17.8% and 64.3% in bulk and root zone, respectively. Similarly, the SOC stock under switchgrass was also 16.5% and 93.0% higher in bulk and root zone than in reference marginal land, respectively. The higher SOC stock in the root zone of switchgrass relative to Miscanthus was supported by the higher contribution of C4‐derived C to SOC (44.5% vs. 32.4%). The mean residence time of old C was higher under switchgrass than Miscanthus in the bulk zone across 0–60 cm (p

Abstract Perennial energy crops (PECs) such as Miscanthus spp. and switchgrass (Panicum virgatum L.) may have particular influence on microbial communities and their functions in soil organic carbon (C) utilization and mineralization (Cm). In this study, long‐term effects of PECs on Cm and soil hydrolase activities were examined in bulk and rhizosphere soils of Miscanthus and switchgrass grown on a red soil in South China. Long‐term cultivation (10 years) of PECs led to increases in soil organic C (SOC) and the absolute Cm of bulk and rhizosphere soils. Total Cm was correlated with dissolved organic C and dissolved organic nitrogen (N) in red soils. The specific Cm in bulk soils of switchgrass and Miscanthus were decreased by 11.73% and 20.67% comparing with the control group, respectively. Cultivation of PECs led to a relatively high C/N ratio. There was a difference in priming effect on activities of β‐glucosidase (BG), leucine amin peptidase, N‐acetyl‐β‐glucosaminidase (NAG), and phosphatase between rhizosphere and bulk soils. Compared with the control without PECs, BG activity did not change significantly in bulk soils of PECs, whereas NAG activity decreased significantly. Soil microorganisms were generally limited by soil C and phosphorus (P) in the red soil. The C and P limitations were significantly linearly related with relative Cm (p

Abstract As interference waves in deep reflection data processing, surface waves are often suppressed as noise, but surface waves carry considerable underground media information, including structural information and the physical properties of rocks. Reasonable extraction and use of surface wave signals are of great significance when studying shallow characteristics. Deep reflection data are collected using large offsets, trail spacing, and explosive sources. The surface wave energy tends to be stronger, and the high-frequency surface wave signal is abundant. After extraction and inversion, the shallow shear wave velocity structure can be obtained. Near the Cuonadong dome in the southern Tibetan detachment system (STDS), a large number of leucogranites are developed in the core, containing important rare metal minerals and high metallogenic potential. However, studies regarding the shallow structure in this region are rare. In this paper, we use deep reflection data from a profile through the Cuonadong dome to obtain the S-wave velocity structure of the study area by extracting the surface wave fundamental-mode dispersion curve and inversion. Combined with regional geological and magnetotelluric data, we supposed that the thickness of the Cuonadong dome sediment layer ( 2.2 km/s), and the horizontal S-wave velocity changes greatly, which is mainly related to the destruction of magmatic activity since the Miocene. These understandings of the structure and velocity field of the Cuonadong dome can provide a powerful geophysical basis for establishing the dome structure model and searching for hidden ore bodies. Graphical abstract

To date, the traditional open thyroid surgery via a low collar incision remains the standard approach for patients undergoing thyroidectomy. However, this conventional approach will inevitably leave patients a neck scar and even cause a variety of complications such as paresthesia, hypesthesia, and other uncomfortable sensations. With the progress in surgical techniques, especially in endoscopic surgery, and the increasing desire for cosmetic and functional outcomes, various new approaches for thyroidectomy have been developed to avoid or decrease side effects. Some of these alternative approaches have obvious advantages compared with traditional surgery and have already been widely used in the treatment of thyroid disease, but each has its limitations. This review aims to evaluate and compare the different approaches to thyroidectomy to help surgeons make the proper treatment strategy for different individuals.

IntroductionCoronavirus disease 2019 (COVID-19) is a global pandemic and highly contagious, posing a serious threat to human health. Colorectal cancer (CRC) is a risk factor for COVID-19 infection. Therefore, it is vital to investigate the intrinsic link between these two diseases.MethodsIn this work, bioinformatics and systems biology techniques were used to detect the mutual pathways, molecular biomarkers, and potential drugs between COVID-19 and CRC.ResultsA total of 161 common differentially expressed genes (DEGs) were identified based on the RNA sequencing datasets of the two diseases. Functional analysis was performed using ontology keywords, and pathway analysis was also performed. The common DEGs were further utilized to create a protein-protein interaction (PPI) network and to identify hub genes and key modules. The datasets revealed transcription factors-gene interactions, co-regulatory networks with DEGs-miRNAs of common DEGs, and predicted possible drugs as well. The ten predicted drugs include troglitazone, estradiol, progesterone, calcitriol, genistein, dexamethasone, lucanthone, resveratrol, retinoic acid, phorbol 12-myristate 13-acetate, some of which have been investigated as potential CRC and COVID-19 therapies.DiscussionBy clarifying the relationship between COVID-19 and CRC, we hope to provide novel clues and promising therapeutic drugs to treat these two illnesses.

Abstract Lipid metabolic reprogramming is one of the important metabolic characteristics of cancer cells. As major components of lipids, fatty acids provide energy and material basis for cancer cell survival. Abnormal fatty acid metabolism has been found in many cancers. Fatty acid uptake, transport, and synthesis are closely related to the pathogenesis of cancer. Meanwhile, fatty acid changes in the membrane structure of cancer cells and signal transduction mediated by signaling lipids are also helping cancer cells survive in the changing microenvironment. Some of these enzymes and metabolites involved in fatty acid metabolism are emerging as unique cancer biomarkers. Multiple studies have shown that disordered fatty acids can regulate tumor cell proliferation, metastasis, and drug resistance. Therefore, targeting fatty acid metabolism has become a promising treatment strategy. Here, we mainly present metabolic alterations of fatty acids, the basic components of lipids, in cancer. We discuss the cancer treatment based on fatty acid and fatty acid metabolism. These may provide a basis for a better understanding of lipid metabolic reprogramming in cancer, and also provide new ideas for cancer biomarker search, drug development, and combination therapy.

A launch vehicle needs to adapt to a complex flight environment during flight, and traditional guidance and control algorithms can hardly deal with multi-factor uncertainties due to the high dependency on control models. To solve this problem, this paper designs a new intelligent flight control method for a rocket based on the deep reinforcement learning algorithm driven by knowledge and data. In this process, the Markov decision process of the rocket landing section is established by designing a reinforcement function with consideration of the combination effect on the return of the terminal constraint of the launch vehicle and the cumulative return of the flight process of the rocket. Meanwhile, to improve the training speed of the landing process of the launch vehicle and to enhance the generalization ability of the model, the strategic neural network model is obtained and trained via the form of a long short-term memory (LSTM) network combined with a full connection layer as a landing guidance strategy network. The proximal policy optimization (PPO) is the training algorithm of reinforcement learning network parameters combined with behavioral cloning (BC) as the reinforcement learning pre-training imitation learning algorithm. Notably, the rocket-borne environment is transplanted to the Nvidia Jetson TX2 embedded platform for the comparative testing and verification of this intelligent model, which is then used to generate real-time control commands for guiding the actual flying and landing process of the rocket. Further, comparisons of the results obtained from convex landing optimization and the proposed method in this work are performed to prove the effectiveness of this proposed method. The simulation results show that the intelligent control method in this work can meet the landing accuracy requirements of the launch vehicle with a fast convergence speed of 84 steps, and the decision time is only 2.5 ms. Additionally, it has the ability of online autonomous decision making as deployed on the embedded platform.

A series of extensional structures, including the southern Tibet detachment system (STDS), the north-south trending rifts (NSTR), and the northern Himalayan gneiss dome (NHGD), developed from the collision and compression between the Indian and Eurasian plates. These tectonic movements were accompanied by magmatism and polymetallic mineralization. Cuona Rift (CR) is located on the STDS next to the Yalaxiangbo Dome (YD) and passes through the Zhegucuo-longzi fault (ZLF), the Lhozhag fault (LZF), the Rongbu-Gudui fault (RGF), the Cuonadong dome (CD), and the YD. The study area contains numerous metal deposits, such as rare metal ore, lead zinc ore, gold deposits, and two geothermal fields, i.e., the Cuona geothermal field (CGF) and the Gudui geothermal field (GGF). Current research on the geological structures from the STDS to the YD is mainly based on magnetotelluric and natural seismic imaging. These surveys have a low resolution, making it impossible to image the shallow crust in detail. This study obtained about a 112 km S-wave velocity profile from the STDS to the YD using the multichannel surface wave imaging method. The profile results indicated that the average thickness of the sedimentary layer from the STDS to the YD is 400–500 m, while it is more than 800 m at certain fault zones. The CD is connected to the high-velocity body below the Zhaxikang ore concentration area (ZOCA) and may have the same provenance. The thermal conductivity reveals that the CGF, the GGF, and the ZOCA have high values and a more intense thermal radiation capacity. This drives the migration and circulation of the thermal fluids in the CGF and the GGF, causing them to continuously transmit heat to the shallow surface along the fault system. The migration of the thermal fluids extracts useful elements from the geological bodies through which it flows. When these elements mix with the atmospheric infiltration water, it precipitates to form the Zhaxikang hydrothermal superimposed transformation type lead-zinc polymetallic deposit.

SARS-CoV-2 proteases are key targets for anti-viral drug development. Here the authors present modular tunable autoproteolytic gene switches for virus free cell culture screening of inhibitors.

Abstract Next‐generation gene and engineered‐cell therapies benefit from incorporating synthetic gene networks that can precisely regulate the therapeutic output in response to externally administered signal inputs that are safe, readily bioavailable and pleasant to take. To enable such therapeutic control, a mammalian gene switch is designed to be responsive to the natural sweetener xylose and its functionality is assessed in mouse studies. The gene switch consists of the bacterial transcription regulator XylR fused to a mammalian transactivator, which binds to an optimized promoter in the presence of xylose, thereby allowing dose‐dependent transgene expression. The sensitivity of SWEET (sweetener‐inducible expression of transgene) is improved by coexpressing a xylose transporter. Mice implanted with encapsulated SWEET‐engineered cells show increased blood levels of cargo protein when taking xylose‐sweetened water or coffee, or highly concentrated apple extract, while they do not respond to intake of a usual amount of carrots, which contain xylose. In a proof‐of‐concept therapeutic application study, type‐1 diabetic mice engineered with insulin‐expressing SWEET show lowered glycemia and increased insulin levels when administered this fairly diabetic‐compliant sweetener, compared to untreated mice. A SWEET‐based therapy appears to have the potential to integrate seamlessly into patients’ life‐style and food habits in the move toward personalized medicine.

Trace elements, such as iodine and selenium (Se), are vital to human health and play an essential role in metabolism. They are also important to thyroid metabolism and function, and correlate with thyroid autoimmunity and tumors. Other minerals such as iron (Ir), lithium (Li), copper (Co), zinc (Zn), manganese (Mn), magnesium (Mg), cadmium (Cd), and molybdenum (Mo), may related to thyroid function and disease. Normal thyroid function depends on a variety of trace elements for thyroid hormone synthesis and metabolism. These trace elements interact with each other and are in a dynamic balance. However, this balance may be disturbed by the excess or deficiency of one or more elements, leading to abnormal thyroid function and the promotion of autoimmune thyroid diseases and thyroid tumors.The relationship between trace elements and thyroid disorders is still unclear, and further research is needed to clarify this issue and improve our understanding of how trace elements mediate thyroid function and metabolism. This paper systematically reviewed recently published literature on the relationship between various trace elements and thyroid function to provide a preliminary theoretical basis for future research.

Cultivating the dedicated biomass crop Miscanthus on marginal land is a sustainable means of avoiding competition with food crops for arable land. A large proportion of global marginal land is saline–alkaline; however, little is known about the performance of Miscanthus in saline-alkaline soil. In this study, Miscanthus × giganteus and ten other Miscanthus hybrids grown in the Yellow River Delta were exposed to low and saline–alkaline soils during the 2016–2018 growing season to evaluate the agronomic traits, biomass quality and the potential productive index of eleven Miscanthus genotypes. Plant biomass, plant height, and tiller number significantly decreased in high saline–alkaline soil. In particular, the average plant biomass of ten Miscanthus hybrids in low saline–alkaline soil in 2017 and 2018 were 0.21 and 2.25 kg per plant, respectively, and in high saline-alkaline soil were 0.13 and 0.65 kg per plant, respectively. Cell wall, cellulose, and nitrogen content of all genotypes significantly decreased in high saline–alkaline soil, while hemicellulose, ash, sodium, potassium, magnesium, and calcium content significantly increased. However, high saline–alkaline soil had no observable impact on lignin content of Miscanthus biomass. The effect of high saline-alkaline on biomass quality parameters could provide important information for the application of Miscanthus biomass in saline-alkaline soil. The selected genotypes (A5) could be considered as breeding materials in saline-alkaline soil.

Transarterial embolization (TAE) is a personalized technology that offers precise delivery of chemotherapeutic drugs or selective internal radiation therapy for hepatocellular carcinoma (HCC). Beta-emitting radionuclide embolisms for TAE (β-based TARE) are commonly used in the clinic via inducing biochemical lethality on tumor cells, while alpha-emitting radionuclides-based embolisms for TAE (α-based TARE) are still under study. The feeding artery plays a key role in tumor growth, metastasis, and recurrence. In this research, the auricular central arteries (ACAs) of rabbits were embolized with silk fibroin-based microspheres (SFMs) or SFMs integrated with α (Ra-223) or β (I-131) radionuclides to investigate the influence on vessels. TARE-induced tissue necrosis and the following neovascularization were measured by pathological analysis and 68Ga-DOTA-RGD PET/CT. The results showed that, compared to I-131, Ra-223 enhanced the growth inhibition of human hepatoma cells Huh-7 and induced more DNA double-strand breaks in vascular smooth muscle cells. Unlike β-based TARE, which mainly led to extensive necrosis of surrounding tissues, α-based TARE induced irreversible necrosis of a limited area adjacent to the embolized vessels. RGD PET revealed the inhibition on neovascularization in α-based TARE (SUVmax = 0.053 ± 0.004) when compared with normal group (SUVmax = 0.099 ± 0.036), the SFMs-lipiodol group (SUVmax = 0.240 ± 0.040), and β-based TARE (SUVmax = 0.141 ± 0.026), owing to the avoidance of the embolism-induced neovascularization. In conclusion, α-based TARE provided a promising strategy for HCC treatments via destroying the embolized vessels and inhibiting neovascularization.

BackgroundHigh serum triglyceride (STG) level is a well-established pathogenic factor for cardiovascular diseases and is associated with the risk of various malignancies. Nevertheless, the role of STG level in intrahepatic cholangiocarcinoma (ICC) remains uncertain.MethodsA total of 631 ICC patients treated with curative hepatectomy in two centers (517 in the discovery set and 114 in the validation set) were retrospectively analyzed. Kaplan–Meier survival analysis was used to assess the outcomes of the patients with different STG levels. Time-dependent receiver operating characteristic (ROC) analysis was conducted to compare the prognostic value of STG with other established indexes. The Triglyceride-Albumin-Globulin (TAG) grade was introduced and evaluated using the time-dependent area under curves (AUC) analysis and decision curve analysis (DCA).ResultsPatients with increased STG levels and decreased albumin-globulin score (AGS) were correlated with improved overall survival (OS) and recurrence-free survival (RFS). STG level ≥ 1 mmol/L was an independent protective factor for surgically treated ICC patients. The predictive value of the TAG grade was superior to the STG or the AGS alone. In decision curve analysis, the net benefits of the TAG grade in the discovery and validation set were higher than STG and AGS.ConclusionThe current study presented strong evidence that ICC patients with higher preoperative STG levels had preferred long-term surgical outcomes. The novel nutritional score based on serum triglyceride, albumin and globulin levels was inextricably linked to the prognosis of the surgically treated ICC patients. Evaluation of the TAG grade before curative hepatectomy may be beneficial for risk stratification and clinical decision support.

AimsDiabetic nephropathy (DN) is one of the main causes of chronic kidney disease (CKD), which increases the risk of cardiovascular diseases and progresses to end-stage renal failure. Thus, early diagnostic markers for diabetic patients are urgently needed to improve the prognosis of DN and predict DN progression.Materials and methodsPubMed, MEDLINE, EMBASE, and Scopus were searched for publications until February 24, 2021. Review Manager 5.4 software was used for meta-analysis. We performed the heterogeneity test using the I2 statistic: P < 0.1 and I2> 50% meant statistical significance.ResultsWe included 13 studies. The urinary liver-type fatty acid-binding protein (uL-FABP) concentrations in the normal albuminuria group were significantly higher than those in the normal control group without diabetes mellitus (DM) [P = 0.009, SMD 1.72, 95% CI (0.44, 2.99)]. Urinary F-LABP levels were elevated in the macroalbuminuria group compared with those in the microalbuminuria group with DM [P = 0.002, SMD 2.82, 95% CI (1.03, 4.61)]. Urinary L-FABP levels were also significantly increased in the progression and CKD groups compared with non-progression and CKD subjects with DM [P = 0.02, P < 0.00001, respectively]. Furthermore, uL-FABP concentrations were positively correlated with the albumin-to-creatinine ratio and systolic blood pressure in patients with DM [Summary Fisher’s Z = 0.58 P < 0.00001; Summary Fisher’s Z = 0.24 P < 0.0001, respectively] and negatively correlated with estimated glomerular filtration rate in patients with DM [Summary Fisher’s Z = −0.36, P < 0.0001].ConclusionUrinary L-FABP may be a potential marker for the detection of all stages of DN and for the prediction of the progression and severity of DN in patients with type 1 and 2 DM.

Indoor localization and navigation have become an increasingly important problem in both industry and academia with the widespread use of mobile smart devices and the development of network techniques. The Wi-Fi-based technology shows great potential for applications due to the ubiquitous Wi-Fi infrastructure in public indoor environments. Most existing approaches use trilateration or machine learning methods to predict locations from a set of annotated Wi-Fi observations. However, annotated data are not always readily available. In this paper, we propose a robot-aided data collection strategy to obtain the limited but high-quality labeled data and a large amount of unlabeled data. Furthermore, we design two deep learning models based on a variational autoencoder for the localization and navigation tasks, respectively. To make full use of the collected data, a hybrid learning approach is developed to train the models by combining supervised, unsupervised and semi-supervised learning strategies. Extensive experiments suggest that our approach enables the models to learn effective knowledge from unlabeled data with incremental improvements, and it can achieve promising localization and navigation performance in a complex indoor environment with obstacles.

Abstract Phytoremediation using Miscanthus is a valuable technique for the restoration of saline‐alkaline soil, but the potential is not quantified. To assess this potential, a 5 years field experiment was conducted on saline‐alkaline soils with three genotypes of Miscanthus and an unplanted control. The bulk soil (0–20‐cm depth) physicochemical properties were measured annually from 2015 to 2018, while the bacterial and fungal community structures of the rhizosphere soil were investigated by high‐throughput sequencing after 5 years under Miscanthus (2018). The results showed that Miscanthus cultivation on saline‐alkaline soil reduced soil salinization and improved soil fertility on this site. Specifically, compared with the blank control, the five‐years Miscanthus cultivation (mean of three different genotypes pooled) decreased the soil pH by 0.33 units (8.78–8.45) and electrical conductivity by 23.4 μS/cm (226.7–203.3 μS/cm), as well as increasing soil organic matter content from 18.9 to 34.9 g/kg and total potassium content from 15.2 to 18.0 g/kg. In addition, the soil improvement was more pronounced with a longer duration of growth. Miscanthus remediates saline‐alkaline soils by altering the microbial community compositional abundance rather than its diversity. The improvement is due to enrichment of beneficial bacteria leading to soil desalinization (e.g., by Gemmatimonadaceae), litter decomposition (e.g., by Chitinophagaceae), plant growth promotion (e.g., by Micrococcaceae), and the reduction of harmful fungi (e.g., Pleosporales and Chitinophagaceae). Soil pH, electrical conductivity, organic matter, and total potassium were the main physicochemical properties affecting bacterial and fungal communities. Our results quantify the soil improvement potential of Miscanthus and clarify the underlying microbial mechanisms, laying a solid foundation for further implementation of saline‐alkaline soil phytoremediation using Miscanthus. In the future, more extensive multi‐location trials are required to assess if these improvements are seen across a wide diversity of environments.

Abstract Miscanthus, a perennial rhizomatous C4 grass, has emerged as a promising lignocellulosic crop. To avoid competition with food crops, marginal lands especially saline–alkaline soil are being recommended to grow Miscanthus across China. However, the challenges such as high cost and low reproduction coefficient associated with the propagation methods are impeding its large‐scale plantation in saline–alkaline soil. In this study, a “two‐steps” propagation method was designed, which was comprised of two phases: (1) seedling cultivation and (2) seedling strengthening. The parameters (substrate composition and plug size) for this method were determined. The optimal substrate composition of the seedling bed for M. sinensis, M. lutarioriparius, and their interspecific hybrids was peat and perlite at a ratio of 3:2, 3:1, and 3:3 by volume, respectively. The seedlings were transplanted into the plugs to deliver robust plantlets. The most appropriate plug size for M. sinensis, M. lutarioriparius, and their interspecific hybrids was 50 plugs (50 cm3/plug), 72 plugs (40 cm3/plug), and 72 plugs (40 cm3/plug), respectively. Three propagation methods, that is, direct sowing of seeds, rhizomes plantation, and “two‐steps” seed‐derived plugs for M. lutarioriparius were compared in saline–alkaline soil over 3 years (2014, 2015, and 2016). The establishment rate of the seeds directly planted was poor (zero). The performance (e.g., biomass yield) of the plants derived from the “two‐steps” seed‐derived plugs was better than that of the plants derived from rhizomes directly planted. Therefore, the “two‐steps” seed‐derived plugs can be regarded as an effective propagation method to upscale Miscanthus cultivation in saline–alkaline soil.

Wearable smart devices often have green light diodes to monitor health. Here the authors use this to control a light-activated genetic switch for GLP1 production in diabetic mice.

Abstract Background It has been reported that long-chain non-coding RNA (lncRNA) zinc finger E-box binding homeobox 1 antisense 1 (ZEB1-AS1) is an oncogene in various cancers, including hepatocellular carcinoma (HCC). We investigated the role and mechanism of ZEB1-AS1 as a competitive endogenous RNA (ceRNA) combined with miR-23c in HCC cell proliferation and invasion. Methods QRT-PCR was used to detect ZEB1-AS1 and miR-23c expressions in HCC tissues and cells. The dual luciferase reporter assay detected the targeted regulation of miR-23c and ZEB1-AS1. We also performed the correlation analysis of their expression in HCC tissues by the Spearman’s correlation analysis. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to detect the proliferation of hepatoma cells. Cell invasion was assessed by the Transwell assay. Results QRT-PCR results indicated ZEB1-AS1 was upregulated and miR-23c was downregulated in HCC tissues and cell lines. ZEB1-AS1 knockdown hampered the proliferation and invasion of HCC cells. Dual luciferase reporter assay showed that miR-23c is a target of ZEB1-AS1, and ZEB1-AS1 was significantly negatively correlated with the miR-23c expression in HCC tissues. The results of MTT and Transwell assay showed that miR-23c inhibition restored the inhibitory effect of ZEB1-AS1 knockdown on HCC cells proliferation and invasion. Conclusions As a ceRNA, lncRNA ZEB1-AS1 may play a vital role in inhibiting HCC progression through miR-23c, which will provide new clues and theoretical basis for the HCC diagnosis and treatment.

Abstract Rapid insulin release plays an essential role in maintaining blood‐glucose homeostasis in mammalians. Patients diagnosed with type‐I diabetes mellitus experience chronic and remarkably high blood‐sugar levels, and require lifelong insulin injection therapy, so there is a need for more convenient and less invasive insulin delivery systems to increase patients’ compliance and also to enhance their quality of life. Here, an endoplasmic‐reticulum‐localized split sec‐tobacco etch virus protease (TEVp)‐based rapamycin‐actuated protein‐induction device (RAPID) is engineered, which is composed of the rapamycin‐inducible dimerization domains FK506 binding protein (FKBP) and FKBP‐rapamycin binding protein fused with modified split sec‐TEVp components. Insulin accumulation inside the endoplasmic reticulum (ER) is achieved through tagging its C‐terminus with KDEL, an ER‐retention signal, spaced by a TEVp cleavage site. In the presence of rapamycin, the split sec‐TEVp‐based RAPID components dimerize, regain their proteolytic activity, and remove the KDEL retention signal from insulin. This leads to rapid secretion of accumulated insulin from cells within few minutes. Using liver hydrodynamic transfection methodology, it is shown that RAPID quickly restores glucose homeostasis in type‐1‐diabetic (T1DM) mice treated with an oral dose of clinically licensed rapamycin. This rapid‐release technology may become the foundation for other cell‐based therapies requiring instantaneous biopharmaceutical availability.

ObjectivePostoperative neck symptoms, including pain, swelling, uncomfortable feelings during swallowing, and incision adhesion formation, are common in patients after lobectomy through the traditional middle neck approach. A new unilateral supraclavicular approach is proposed to protect the anterior cervical region and reduce related complications. The aim of this study is to investigate the efficacy, safety, and advantages of the supraclavicular approach in lobectomy for unilateral papillary thyroid microcarcinoma (PTMC).MethodsTwo hundred sixty-three patients were recruited into either a conventional middle group (CM) or a new supraclavicular (NS) group. Clinicopathological features, surgically related variables, and postoperative symptoms were recorded. Quality of life (QOL) of all patients was assessed by the 12-item short-form health survey (SF-12) and thyroid cancer-specific QOL (THYCA-QoL) questionnaire in 3 and 12 months.ResultsThere were no statistically significant differences in clinicopathological features (including sex, age, multifocality, extrathyroidal extension, histological variants, largest tumor diameter, Hashimoto’s thyroiditis, metastasized central lymph node, removed central lymph node, surgeon, BRAF mutation, and follow-up duration), hospitalization (including hospital cost, surgery time, and blood loss during surgery), and complications between the two groups. Patients who underwent lobectomy through the NS approach had significantly better SF-12 physical, mental, and THYCA-QoL than the CM group patients in both 3 and 12 months (all p < 0.001). Moreover, the NS group had a shorter hospitalization time.ConclusionIn conclusion, the NS approach for lobectomy is a safe and effective method for reducing postoperative symptoms and increasing QOL in patients with unilateral PTMC in both 3 and 12 months’ follow-up.

To improve the material removal efficiency and surface quality of single-crystal silicon after magnetorheological finishing, a novel green chemical-mechanical magnetorheological finishing (CMMRF) fluid was developed. The main components of the CMMRF fluid are nano-Fe3O4, H2O2, CH3COOH, nanodiamond, carbonyl iron powder, and deionized water. The novel CMMRF fluid can simultaneously achieve Ra 0.32 nm (0.47 mm × 0.35 mm measurement area), Ra 0.22 nm (5 μm × 5 μm measurement area), and 1.91 × 10−2 mm3/min material removal efficiency. Comprehensive studies utilizing a scanning electron microscope and a magnetic rheometer show that the CMMRF fluid has a high mechanical removal effect due to the well-dispersed nanodiamond and nano-Fe3O4 particles. The results of Fourier transform infrared spectra and Young’s modulus test reveal the mechanism of the chemical reaction and the mechanical characteristics deterioration of the modified layer. Under co-enhanced chemical and mechanical effects, an ultra-smooth and highly efficient MRF technology for single-crystal silicon is realized.

Abstract Body temperature is maintained at around 37 °C in humans, but may rise to 40 °C or more during high‐grade fever, which occurs in most adults who are seriously ill. However, endogenous temperature sensors, such as ion channels and heat‐shock promoters, are fully activated only at noxious temperatures above this range, making them unsuitable for medical applications. Here, a genetically encoded protein thermometer (human enhanced gene activation thermometer; HEAT) is designed that can trigger transgene expression in the range of 37–40 °C by linking a mutant coiled‐coil temperature‐responsive protein sensor to a synthetic transcription factor. To validate the construct, a HEAT‐transgenic monoclonal human cell line, FeverSense, is generated and it is confirmed that it works as a fever sensor that can temperature‐ and exposure‐time‐dependently trigger reporter gene expression in vitro and in vivo. For translational proof of concept, microencapsulated designer cells stably expressing a HEAT‐controlled insulin production cassette in a mouse model of type‐1 diabetes are subcutaneously implanted and topical heating patches are used to apply heat corresponding to a warm sensation in humans. Insulin release is induced, restoring normoglycemia. Thus, HEAT appears to be suitable for practical electrothermal control of cell‐based therapy, and may also have potential for next‐generation treatment of fever‐associated medical conditions.