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Transient global amnesia is common in the older adult, but the cause and mechanism remain unclear. Focal brain lesions allow for causal links between the lesion location and resulting symptoms, and we based on the reported TGA-causing lesions and used lesion network mapping to explore the causal neuroanatomical substrate of TGA.Fifty-one cases of transient global amnesias with DWI lesions from the literature were identified, and clinical data were extracted and analyzed. Next, we mapped each lesion volume onto a reference brain and computed the network of regions functionally connected to each lesion location using a large normative connectome dataset.Lesions primarily occurred in the hippocampus, and in addition to the hippocampus, there are also other locations of TGA-causing lesions such as the cingulate gyrus, anterior thalamic nucleus (ATN), putamen, caudate nucleus, corpus callosum, fornix. More than 90% of TGA-causing lesions inside the hippocampus were functionally connected with the default mode network (DMN).Structural abnormality in the hippocampus was the most consistently reported in TGA, and besides the hippocampus, lesions occurring at several other brain locations also could cause TGA. The DMN may also be involved in the pathophysiology of TGA. According to the clinical and neuroimaging characteristics, TGA may be a syndrome with multiple causes and cannot be treated simply as a subtype of TIA.

Objectives Patients with vascular anomalies (VAs) who receive oral sirolimus may be at high risk of infectious complications. Antibiotic prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMZ) has been advocated. However, there have been few evidence-based analyses on this topic. This study assessed the effect of prophylactic TMP-SMZ on the incidence of infections in VA patients receiving sirolimus monotherapy. Methods A retrospective, multicenter chart review was performed on all VA patients receiving sirolimus treatment from August, 2013 to January, 2021. Results Before January 2017, 112 patients were treated with sirolimus without antibiotic prophylaxis. In the subsequent period, 195 patients were treated with TMP-SMZ for at least 12 months during sirolimus therapy. The percentage of patients with at least one serious infection during the initial 12 months of sirolimus treatment did not differ between the groups (difference, 1.1%; 95% CI − 7.0–8.0%). We observed no difference in the incidence of individual infection or total adverse events between the groups. The rate of sirolimus discontinuation due to adverse events did not differ significantly between groups. Conclusions We demonstrated that prophylactic TMP-SMZ does not decrease the incidence of infection or improve tolerance in VA patients receiving sirolimus monotherapy.

Background As the rate of multiple pregnancies increases, delayed interval delivery (DID) is increasingly being implemented to improve perinatal outcomes. But there are no international guidelines for DID in multiple pregnancies. We report a case of DID in a quadruplet pregnancy and review the relevant literature to summarize the management of DID in multiple pregnancies. Case presentation A 22-year-old woman, 22 2/7 weeks' gestation, with quadruplets, was admitted to the hospital for a first cervical cerclage due to cervical dilation. Twenty-five days later, it was found that the cervix was dilated again, so after removing the cervical cerclage, the first quadruplet was delivered vaginally (25 6/7 weeks), and a second cervical cerclage was performed. Four days later, due to re-dilation of the cervix, after removal of the cervical cerclage, the second quadruplet was delivered vaginally (26 3/7 weeks), followed by a third cervical cerclage. Six days later, the pregnancy was terminated by cesarean section due to fetal distress, and the third and fourth quadruplets were delivered (27 2/7 weeks). The patient had no postoperative complications, and all four infants were treated in the neonatal intensive care unit and discharged successfully. Conclusion This case emphasizes that comprehensive management of delayed interval delivery can improve perinatal outcomes in multiple pregnancies, including anti-infection, tocolytic therapy, practice to promote fetal lung, and cervical cerclage.

Breast cancer is the most common cancer affecting women worldwide. Many genes are involved in the development of breast cancer, including the Kruppel Like Factor 12 (KLF12) gene, which has been implicated in the development and progression of several cancers. However, the comprehensive regulatory network of KLF12 in breast cancer has not yet been fully elucidated. This study examined the role of KLF12 in breast cancer and its associated molecular mechanisms. KLF12 was found to promote the proliferation of breast cancer and inhibit apoptosis in response to genotoxic stress. Subsequent mechanistic studies showed that KLF12 inhibits the activity of the p53/p21 axis, specifically by interacting with p53 and affecting its protein stability via influencing the acetylation and ubiquitination of lysine370/372/373 at the C-terminus of p53. Furthermore, KLF12 disrupted the interaction between p53 and p300, thereby reducing the acetylation of p53 and stability. Meanwhile, KLF12 also inhibited the transcription of p21 independently of p53. These results suggest that KLF12 might have an important role in breast cancer and serve as a potential prognostic marker and therapeutic target.

Infantile hemangioma (IH) is the most prevalent benign vascular tumor in infants, with distinct disease stages and durations. Despite the fact that the majority of IHs can regress spontaneously, a small percentage can cause disfigurement or even be fatal. The mechanisms underlying the development of IH have not been fully elucidated. Establishing stable and reliable IH models provides a standardized experimental platform for elucidating its pathogenesis, thereby facilitating the development of new drugs and the identification of effective treatments. Common IH models include the cell suspension implantation model, the viral gene transfer model, the tissue block transplantation model, and the most recent three-dimensional (3D) microtumor model. This article summarizes the research progress and clinical utility of various IH models, as well as the benefits and drawbacks of each. Researchers should select distinct IH models based on their individual research objectives to achieve their anticipated experimental objectives, thereby increasing the clinical relevance of their findings.

Prostate cancer (PCa) is the second most prevalent malignancy in males across the world. A greater knowledge of the relationship between protein abundance and drug responses would benefit precision treatment for PCa. Herein, we establish 35 Chinese PCa primary cell models to capture specific characteristics among PCa patients, including gene mutations, mRNA/protein/surface protein distributions, and pharmaceutical responses. The multi-omics analyses identify Anterior Gradient 2 (AGR2) as a pre-operative prognostic biomarker in PCa. Through the drug library screening, we describe crizotinib as a selective compound for malignant PCa primary cells. We further perform the pharmacoproteome analysis and identify 14,372 significant protein-drug correlations. Surprisingly, the diminished AGR2 enhances the inhibition activity of crizotinib via ALK/c-MET-AKT axis activation which is validated by PC3 and xenograft model. Our integrated multi-omics approach yields a comprehensive understanding of PCa biomarkers and pharmacological responses, allowing for more precise diagnosis and therapies.

Background Non-involuting congenital hemangiomas (NICHs) are fully formed vascular tumors at birth with distinctive clinical, radiologic, and histopathological profiles. In the literature, there is no effective therapy strategy for patients with NICH except surgery. Currently, no cell line or animal model exists for studying the mechanism of NICH and drug validation. We plan to construct a new strategy by constructing NICH organoids for further study. Result Here, we report a novel NICH organoid system construction and optimization process. Both HE and immunohistological staining exactly matched NICH tissue. We further performed transcriptome analysis to elucidate the characteristics of NICH organoids. Both NICH tissue and NICH organoids manifested similar trends in download sites. NICH organoids display novel features to new cells derived from organoids and show spectacular multiplication capacity. In the preliminary verification, we found that cells splitting from NICH organoids were human endothelial cells. Drug validation demonstrated that trametinib, sirolimus, and propranolol showed no inhibitory effects on NICH organoids. Conclusion Our data show that this new NICH-derived organoid faithfully captured the features of this rare vascular tumor. Our study will boost further research on the mechanism of NICH and drug filtering in the future.

Hypertension is a global public health issue and the leading cause of premature death in humans. Despite more than a century of research, hypertension remains difficult to cure due to its complex mechanisms involving multiple interactive factors and our limited understanding of it. Hypertension is a condition that is named after its clinical features. Vascular function is a factor that affects blood pressure directly, and it is a main strategy for clinically controlling BP to regulate constriction/relaxation function of blood vessels. Vascular elasticity, caliber, and reactivity are all characteristic indicators reflecting vascular function. Blood vessels are composed of three distinct layers, out of which the endothelial cells in intima and the smooth muscle cells in media are the main performers of vascular function. The alterations in signaling pathways in these cells are the key molecular mechanisms underlying vascular dysfunction and hypertension development. In this manuscript, we will comprehensively review the signaling pathways involved in vascular function regulation and hypertension progression, including calcium pathway, NO-NOsGC-cGMP pathway, various vascular remodeling pathways and some important upstream pathways such as renin-angiotensin-aldosterone system, oxidative stress-related signaling pathway, immunity/inflammation pathway, etc. Meanwhile, we will also summarize the treatment methods of hypertension that targets vascular function regulation and discuss the possibility of these signaling pathways being applied to clinical work.

As the particularly popular green energy, geothermal resources are gradually favored by countries around the world, and the development model centered on geothermal dew point cannot meet the increasing geothermal demand. In this paper, a GIS model combining PCA and AHP is proposed, aiming to select the advantages of geothermal resources at the regional scale and analyze the main influencing indicators. Through the combination of the two methods, both data and empirical can be considered, then the geothermal advantage distribution on the area can be displayed through GIS software images. A multi-index evaluation system is established to qualitatively and quantitatively evaluate the mid-high temperature geothermal resources in Jiangxi Province, and carry out the evaluation of the dominant target areas and the analysis of geothermal impact indicators. The results show that it is divided into 7 geothermal resource potential areas and 38 geothermal advantage targets, and the determination of deep fault is the most critical index of geothermal distribution. This method is suitable for large-scale geothermal research, multi-index and multi-data model analysis and precise positioning of high-quality geothermal resource targets, which can meet the needs of geothermal research at the regional scale.

Background The peaberry bean in Arabica coffee has exceptional quality compared to the regular coffee bean. Understanding the molecular mechanism of bean quality is imperative to introduce superior coffee quality traits. Despite high economic importance, the regulatory aspects of bean quality are yet largely unknown in peaberry. A transcriptome analysis was performed by using peaberry and regular coffee beans in this study. Results The result of phenotypic analysis stated a difference in the physical attributes of both coffee beans. In addition, transcriptome analysis revealed low genetic differences. Only 139 differentially expressed genes were detected in which 54 genes exhibited up-regulation and 85 showed down-regulations in peaberry beans compared to regular beans. The majority of differentially expressed genes had functional annotation with cell wall modification, lipid binding, protein binding, oxidoreductase activity, and transmembrane transportation. Many fold lower expression of Ca25840-PMEs1, Ca30827-PMEs2, Ca30828-PMEs3, Ca25839-PMEs4, Ca36469-PGs. and Ca03656-Csl genes annotated with cell wall modification might play a critical role to develop different bean shape patterns in Arabica. The ERECTA family genes Ca15802-ERL1, Ca99619-ERL2, Ca07439-ERL3, Ca97226-ERL4, Ca89747-ERL5, Ca07056-ERL6, Ca01141-ERL7, and Ca32419-ERL8 along lipid metabolic pathway genes Ca06708-ACOX1, Ca29177-ACOX2, Ca01563-ACOX3, Ca34321-CPFA1, and Ca36201-CPFA2 are predicted to regulate different shaped bean development. In addition, flavonoid biosynthesis correlated genes Ca03809-F3H, Ca95013-CYP75A1, and Ca42029-CYP75A2 probably help to generate rarely formed peaberry beans. Conclusion Our results provide molecular insights into the formation of peaberry. The data resources will be important to identify candidate genes correlated with the different bean shape patterns in Arabica.

Postoperative cognitive dysfunction (POCD) remains one of the most common complications following anesthesia and surgery (AS) in the elderly population. Calcium-mediated mitochondrial injury has been proved to induce cognitive impairment in a variety of neurologic diseases. In the current study we determined whether electro-acupuncture (EA) pretreatment ameliorated AS-induced POCD in aged rats, as well as the underlying mechanism. Eighty SD rats (18 months, male) were randomly assigned into four groups (n = 20): C, C + EA, POCD and EA + POCD. Rats in Group POCD and EA + POCD were subjected to exploratory laparotomy under sevoflurane anesthesia. Rats of Group C + EA and EA + POCD received a 5-day EA stimulation at Hegu, Neiguan and Zusanli acupoints before AS. At 3rd day after AS, open field test along with Morris water maze test were employed to examine the cognitive function of aged rats. Then hippocampal tissues were stripped and hippocampal neuronal amount, expression level of cleaved caspase-9 level, cytochrome c (Cyt C), cleaved caspase-3 level, Bcl-2, Bax, ROS expression level, apoptosis rate, mitochondrial membrane potential (MMP), cytosolic calcium concentration ([Ca

In this work, a convenient and dual-signal readout optical sensing platform for the sensitively and selectively determination of beta-glucosidase (β-Glu) activity was reported using protein-inorganic hybrid nanoflowers [BSA-Cu

Postoperative cognitive dysfunction (POCD) induced by anesthesia or surgery has become a common complication in the aged population. Sevoflurane, a clinical inhalation anesthetic, could stimulate calcium overload and necroptosis to POCD. In addition, necroptosis inhibitor necrostatin-1 (Nec-1) alleviated cognitive impairment caused by multiple causes, including postoperative cognitive impairment. However, whether Nec-1 exerts a neuroprotective effect on POCD via calcium and necroptosis remains unclear. We anesthetized Sprague-Dawley rats with sevoflurane to construct the POCD model and to explore the mechanism underlying neuroprotective effects of Nec-1 in POCD. Rats were treated with Nec-1 (6.25 mg/kg) 1 h prior to anesthesia. Open field test and Morris water maze were employed to detect the cognitive function. In this study, rats exposed to sevoflurane displayed cognitive dysfunction without changes in spontaneous activity; however, the sevoflurane-induced POCD could be relieved by Nec-1 pretreatment. Nec-1 decreased sevoflurane-induced calcium overload and calpain activity in the hippocampus. In addition, Nec-1 alleviated the expression of p-RIPK1, RIPK1, p-RIPK3, RIPK3, p-MLKL and MLKL. Furthermore, Nec-1 remarkably increased BDNF and p-TrkB/TrkB expression in the hippocampus of aged rats. Ultimately, our research manifests evidence that Nec-1 may play a neuroprotective role against sevoflurane-induced cognitive impairment via the increase of BDNF/TrkB and suppression of necroptosis-related pathway.

Porcine epidemic diarrhea virus (PEDV) is an enteric coronavirus that causes acute watery diarrhea and vomiting in unweaned piglets, and is associated with high mortality, thus causing severe economic losses in the pig industry. Currently, although attenuated vaccines are commonly used in commercial pig farms in China, they do not completely protect against all mutated wild-type strains. Existing nucleic acid assays have high sensitivity and specificity, but the complexity of the assay process and expensive instrumentation hinder disease detection. Here, reverse transcription–enzymatic recombinase amplification (RT-ERA) was combined with the CRISPR-Cas12a system to develop a rapid diagnostic method to distinguish PEDV wild-type strains from attenuated vaccine strains. The protocol used crRNA and RT-ERA amplification primers against open reading frame 3 (ORF3), followed by Cas12a/crRNA complex detection of predefined target sequences at 37 °C for 30 min, thus producing results visible to the naked eye under LED blue light. The assay is highly sensitive and specific, detecting as few as two copies of the target gene per test and showing no cross-reactivity with other porcine pathogens. Overall, this integrated RT-ERA pre-amplification and Cas12a/crRNA cleavage assay is a practical tool for reliable and rapid detection of PEDV for diagnostic differentiation. Supplementary Information The online version contains supplementary material available at 10.1007/s00216-021-03716-7.

Background Sodium formononetin-3ʹ-sulphonate (Sul-F) may alleviate I/R injury in vivo with uncertain mechanism. Endoplasmic reticulum (ER) stress-mediated apoptosis participates in the process of cerebral ischemia‐reperfusion (I/R) injury. Our aim is to figure out the effect of Sul-F on cerebral I/R injury and to verify whether it works through suppressing ER stress-mediated apoptosis. Results The cerebral lesions of middle cerebral artery occlusion (MCAO) model in SD rats were aggravated after 24 h of reperfusion, including impaired neurological function, increased infarct volume, intensified inflammatory response and poor cell morphology. After intervention, the edaravone (EDA, 3 mg/kg) group and Sul-F high-dose (Sul-F-H, 80 mg/kg) group significantly alleviated I/R injury via decreasing neurological score, infarct volume and the serum levels of inflammatory factors (TNF-α, IL-1β and IL-6), as well as alleviating pathological injury. Furthermore, the ER stress level and apoptosis rate were elevated in the ischemic penumbra of MCAO group, and were significantly blocked by EDA and Sul-F-H. In addition, EDA and Sul-F-H significantly down-regulated the ER stress related PERK/eIF2α/ATF4 and IRE1 signal pathways, which led to reduced cell apoptosis rate compared with the MCAO group. Furthermore, there was no difference between the EDA and Sul-F-H group in terms of therapeutic effect on cerebral I/R injury, indicating a therapeutic potential of Sul-F for ischemic stroke. Conclusions Sul-F-H can significantly protects against cerebral I/R injury through inhibiting ER stress-mediated apoptosis in the ischemic penumbra, which might be a novel therapeutic target for ischemic stroke.

Psoriasis is currently an incurable skin disorder mainly driven by a chronic inflammatory response. We found that subcutaneous application of umbilical cord- derived mesenchymal stem/stromal cells (MSCs) primed by IFN-γ and TNF-α, referred to as MSCs-IT, exhibited remarkable therapeutic efficacy on imiquimod (IMQ)-induced psoriasis-like inflammation in mice. Neutrophil infiltration, a hallmark of psoriasis, was significantly reduced after treatment with MSCs-IT. We further demonstrated that the effects of MSCs-IT were mediated by tumor necrosis factor (TNF) stimulating gene-6 (TSG-6), which was greatly upregulated in MSCs upon IFN-γ and TNF-α stimulation. MSCs transduced with TSG-6 siRNA lost their therapeutic efficacy while recombinant TSG-6 applied alone could also reduce neutrophil infiltration and alleviate the psoriatic lesions. Furthermore, we demonstrated that TSG-6 could inhibit neutrophil recruitment by decreasing the expression of CXCL1, which may be related to the reduced level of STAT1 phosphorylation in the keratinocytes. Thus, blocking neutrophil recruitment by MSCs-IT or TSG-6 has potential for therapeutic application in human psoriasis.

Protein neddylation is catalyzed by a neddylation activating enzyme (NAE, E1), an E2 conjugating enzyme, and an E3 ligase. In various types of human cancers, the neddylation pathway is abnormally activated. Our previous study validated that the neddylation E2 UBE2F is a promising therapeutic target in lung cancer. Although the NAE inhibitor MLN4924/pevonedistat is currently under clinical investigation as an anti-cancer agent, there are no small molecules available that selectively target UBE2F. Here, we report, for the first time, the discovery, via structure-based virtual screen and chemical optimization, of such a small molecule, designated as HA-9104. HA-9104 binds to UBE2F, reduces its protein levels, and consequently inhibits cullin-5 neddylation. Blockage of cullin-5 neddylation inactivates cullin-RING ligase-5 (CRL5) activity, leading to accumulation of the CRL5 substrate, NOXA, to induce apoptosis. Moreover, HA-9104 appears to form the DNA adduct via its 7-azaindole group to induce DNA damage and G2/M arrest. Biologically, HA-9104 effectively suppresses the growth and survival of lung cancer cells and confers radiosensitization in both in vitro cell culture and in vivo xenograft tumor models. In summary, we discovered a small molecule, designated HA-9104, that targets the UBE2F-CRL5 axis with anti-cancer activity alone or in combination with radiation.

T cell receptor excision circles (TRECs) are small circularized DNA elements produced during rearrangement of T cell receptor (TCR) genes. Because TRECs are fairly stable, do not replicate during mitosis, and are not diluted during division of naïve T cells (Dion et al. [1]), they are suitable for assessing the number of newly formed T cells (Ping and Denise [2]). In this study, we detected TRECs in 521 healthy Chinese children aged 0-18 years in different clinical settings. The TRECs decrease with aging and show lower levels in preterm and low birth weight (BW) babies compared to those in full-term infants, while the preterm babies can also show comparable levels of TRECs when they have a gestation age (GA)-matched BW. We found a strong correlation between TRECs and peripheral CD4 naïve T cell numbers, which was age-related. We also analyzed the TRECs in different PIDs. Since T cell defects vary in PIDs, TREC levels change inconsistently. For example, in Wiskott-Aldrich syndrome (WAS), combining the level of TREC with lymphocyte subsets can help to distinguish subtypes of disease.Conclusion: We established the reference value range for TRECs by evaluating children below 18 years old in China, which could be used to screen for PIDs during early life. What is Known: • The TREC levels are decreased with age, and there is a positive correlation between TRECs and the numbers of naïve T cells. What is New: • This is the largest study to determine TREC reference levels in healthy Chinese pediatric, we provide solid data showing a correlation between CD4 naïve T cell counts and TREC levels according to age. We point out the GA matched BW is need to be considered during the SCID newborn screening. We are the first group showed that TREC levels can help clinician distinguish different WAS phenotype.

Research on the roles of the bacteria in tumor development and progression is a rapidly emerging field. Increasing evidence links bacteria with the modification of the tumor immune microenvironment, which greatly influences the antitumor response. In view of the individual immune effects of various bacteria in various tumors, developing personalized bacteria-modulating therapy may be a key to successful antitumor treatment. This review emphasizes the critical role of the bacteria in immune regulation, including both the tumor bacteria and gut bacteria. Aiming at tumor-related bacteria, we focus on various precise modulation strategies and discuss their impact and potential for tumor suppression. Finally, engineered bacteria with tumor-targeting ability could achieve precise delivery of various payloads into tumors, acting as a precision tool. Therefore, a precise tumor-related bacteria therapy may be a promising approach to suppress the development of tumors, as well as an adjuvant therapy to improve the antitumor efficacy of other approaches. KEY POINTS: • The mini-review updates the knowledge on complex effect of bacteria in TME. • Insight into the interaction and adjustment of bacteria in gut for TME. • Prospects and limitations of bacteria-related personalized therapy in the clinical anticancer therapy.

Abstract Macrolide antibiotics are one of the most commonly used broad-spectrum antibiotics. They have an inhibitory effect on a variety of respiratory pathogens; besides, they have non-anti-infective effects, including anti-inflammatory, regulating airway secretion, immune regulation, and other effects. A growing number of studies have shown that the non-anti-infective effects of macrolides have important and potential value in the treatment of pediatric chronic airway diseases; the therapy was described as “long-term, low-dose usage”; unfortunately, there is no guideline or consensus that applies to children. To better carry out the mechanism and clinical research of non-anti-infective effect and promote its rational use in children, the authors summarize the evidence of the usage of long-term, low-dose macrolide antibiotic therapy (LLMAT) in the treatment of chronic airway diseases in children and the progress in recent years. Impact This review summarizes the evidence (mostly in recent 5 years) of the usage of long-term, low-dose macrolide antibiotic therapy in the treatment of chronic airway diseases. The recent studies and guidelines support and enrich the point that long-term, low-dose macrolide antibiotic therapy has potential benefit for children with severe asthma, CF, non-CF bronchiectasis, and BO, which provides clinical references and is of clinical interest. Long-term, low-dose macrolide antibiotic therapy has good safety, and no serious events have been reported; however, potential cardiac side effects and macrolide resistance should be clinically noted.

Ectomycorrhizal fungi (EMF) can enhance drought resistance of host plants by increasing nutrient and water absorption. Calcium (Ca) plays a central role in drought stress adaptation, yet it remains unclear how EMF influence Ca uptake of plants under drought stress. We carried out a pot experiment in which Quercus acutissima seedlings were inoculated with or without the ectomycorrhizal (EM) fungus Xerocomus chrysenteron under control and water stress soil moisture conditions in order to investigate how soil Ca availability and plant Ca uptake are modulated by EMF and how this may contribute to drought resistance of the seedlings. We found that soil water-extractable Ca was significantly reduced by drought in non-ectomycorrhizal treatment, while EM treatment significantly increased soil Ca availability and Ca uptake of Quercus acutissima seedlings under drought conditions. Furthermore, seedling water use efficiency (WUE) was positively correlated with soil Ca availability and plant Ca content. Calcium uptake promotion seems to be involved in the mechanisms of drought tolerance enhancement by EMF.

With the continuous growth of the population and the continuous reduction of cultivated land, China’s food security is greatly threatened. In addition, China’s coal mining has been mainly underground mining, causing land subsidence and damaging existing cultivated land. This effect intensifies the contradiction between the growth of the risk population and the reduction of cultivated land. The reclamation of mining subsidence land with Yellow River sediment is often used as an effective way to improve the recovery rate of cultivated land. Shortening the reclamation time and realizing continuous filling are significant issues. The work presented in this paper studied the sediment settlement rate and consolidation time by combining theory, field filling and reclamation tests and numerical simulations. A field filling test study was carried out in the lowlands of Jibeiwang Village, Qihe County, Shandong Province, China. By calculating the drainage consolidation time, the consolidation factor of 0.015656 m2/d, and the time factor for sediment consolidation of 0.575 were determined. The sediment consolidation time for this test was 9.18 days. The calculation of sediment deposition rate and consolidation time is of great practical significance to guide the Yellow River sediment filling, realize continuous filling, and save reclamation time and cost.

The assessment of the spatiotemporal evolution of habitat quality caused by land use changes can provide a scientific basis for the ecological protection and green development of mining cities. Taking Yanshan County as an example of a typical mining city, this article discussed the spatial pattern and evolution characteristics of habitat quality in 2000 and 2018 based on the ArcGIS platform and the InVEST model. The conclusions are as below: from 2000 to 2018, the area of farmland and construction land changed the most in the study area. Among them, the area of farmland decreased by 3.48%, and the area of industrial and mining land and construction land increased by 53.25%. Areas of low, relatively low and high habitat quality expanded, and areas of medium and relatively high habitat quality shrank, which is closely related to the distribution of land use. The areas with high habitat degradation degrees appear around cities, mining areas and watersheds, while the areas with low habitat degradation degrees are mainly distributed in the southern woodland. The distribution of cold and hot spots in the habitat quality distribution of Yanshan County presents a pattern of “hot in the south and cold in the north”. The results are of great significance to the precise implementation of ecosystem management decisions in mining cities and the creation of a landscape pattern of “beautiful countrysides, green cities, and green mines”.

Although an increasing number of patients benefit from immunotherapy and targeted therapies, melanoma remains incurable with increasing incidence. Drug repositioning and repurposing is an alternative strategy to discover and develop novel anticancer drugs or combined therapeutic regimens. In this study, we demonstrated that albendazole (ABZ), an Food and Drug Administration (FDA)-approved broad-spectrum antiparasitic agent, significantly inhibits the proliferation of melanoma cells in vitro and in vivo. RNA sequencing and flow cytometry analysis revealed that ABZ arrests melanoma cells at the G2/M phase of the cell cycle and induces cell apoptosis. More importantly, the CDK4/6 inhibitor palbociclib, as a member of the first and only class of highly specific CDK inhibitors approved for cancer treatment to date, showed significant synergistic effects with ABZ treatment in melanoma cells and mouse models. Taken together, we revealed a previously unappreciated function of ABZ in antimelanoma proliferation by inducing cell cycle arrest and apoptosis and provided a novel combined therapeutic regimen of ABZ plus CDK4/6 inhibitor treatment in melanoma.

Developing cost-efficient electrocatalysts that are highly efficient and stable for pH-universal hydrogen evolution reaction (HER) is of great significance for scale-up electricity-to-fuel conversion. Herein, we report a free-standing cathode that the Pd NPs are embedded in a porous carbonized wood membrane (Pd@CWM) for efficient pH-universal HER. The 3D CWM not only serves as an effective porous matrix for hosting Pd nanoparticles with high dispersion but also acts as a conductive current collector. More importantly, the aligned open microchannels inside the CWM provide unimpeded pathways for electrolyte transport and gas release. Thanks to these structural benefits, the as-fabricated Pd@CWM electrodes display superior electrocatalytic activity for the HER, and the most efficient Pd@CWM-2 electrode only needs 154 and 302 mV overpotentials to deliver a HER current density of 10 mA cm−2 in 0.5 M H2SO4 and 1.0 M KOH, respectively. More impressively, Pd@CWM-2 electrode also exhibits excellent stability at a high current density (> 50 mA cm−2) for the HER with 100% faradaic efficiencies in both electrolyte solutions. This work provides a promising strategy for designing free-standing carbon membrane–based pH-universal electrode for large-scale clean fuel production.

A period-varying iterative learning control scheme is proposed for a robotic manipulator to learn a target trajectory that is planned by a human partner but unknown to the robot, which is a typical scenario in many applications. The proposed method updates the robot’s reference trajectory in an iterative manner to minimize the interaction force applied by the human. Although a repetitive human–robot collaboration task is considered, the task period is subject to uncertainty introduced by the human. To address this issue, a novel learning mechanism is proposed to achieve the control objective. Theoretical analysis is performed to prove the performance of the learning algorithm and robot controller. Selective simulations and experiments on a robotic arm are carried out to show the effectiveness of the proposed method in human–robot collaboration.

Mesoporous N-doped carbon (m-N-Carbon) nanofibers with controlled numerous surface nanocavities as efficient oxygen reduction reaction electrocatalysts have been fabricated through carbonization polyaniline (PANI) nanofibers decorated with different sizes of SiO2 nanoparticles. The prepared m-N-Carbon nanofibers possess tunable mesopores, high surface area and desired nitrogen moieties. Among these, the sample m-N-Carbon (M-900) exhibits the highest electrocatalytic performance with high onset potential (0.941), half-wave potential (0.713 V), superior catalytic stability with slightly attenuated after 20000-s continuous operation and well tolerance to methanol. The enhanced electrocatalytic activities are associated with high-nitrogen content and the rational design of mesoporous structure N-Carbon nanofibers, which are contributed to the mass/electron transfer and exposure of active sites.

The paper investigates the robustness of pullback attractors and pullback exponential attractors of the non-autonomous Kirchhoff wave models with strong nonlinear damping: $$u_{tt}- (1+\epsilon \Vert \nabla u\Vert ^2)\Delta u-\sigma (\Vert \nabla u\Vert ^2) \Delta u_t+f(u)=g(x,t)$$ , where $$\epsilon \in [0,1]$$ is an extensibility parameter. It shows that when the growth exponent p of the nonlinearity f(u) is up to the supercritical range: $$1\le p

Phenolic compounds are the dominant pollutants in soils contaminated by the coking industry. Ring opening by the hydroxylase gene (bamA) is the key step in the benzoyl-CoA degradation pathway under anaerobic conditions, and a broad spectrum of microorganisms possesses this functional gene, including denitrifiers. The present study analyzed the community structure of denitrifying bacteria and the diversity of the bamA gene for mixed cultures enriched from soil collected at a coking industrial site and then grown under nitrate-reducing conditions on phenol or p-hydroxybenzoate (4HBA), a key intermediate product of anaerobic phenol degradation. Illumina sequencing of the 16S rRNA gene showed different bacterial compositions between the two cultures. The dominant phyla were Proteobacteria, Armatimonadetes, and Planctomycetes in the phenol culture and Proteobacteria and Bacteroidetes in the 4HBA culture. Phylogenetic analysis further demonstrated that bamA genes were associated with four clusters of bacteria, three of known bacteria and one of uncultured bacteria. The diversity of the bamA gene differed from that reported in anaerobic aromatic degradation cultures, suggesting that these enriched cultures may contain new strains unique to coking-contaminated soils. The present study further validates the potential application of this functional gene as a marker for anaerobic biodegradation processes in enrichment cultures from contaminated soil.