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Abstract The major histocompatibility complex class I antigen presentation pathways play pivotal roles in orchestrating immune responses. Recent studies have begun to explore the therapeutic potential of cysteines within the immunopeptidome, such as the use of covalent ligands to generate haptenated peptide neoepitopes for immunotherapy. In this work, we report a platform for mapping reactive cysteines on MHC-I-bound peptide antigens. We develop cell-impermeable sulfonated maleimide probes capable of capturing reactive cysteines on these antigens. Using these probes in chemoproteomic experiments, we discover that cysteines on MHC-I-bound antigens exhibit various degrees of reactivity. Moreover, interferon-gamma stimulation enhances the reactivity of cysteines at position 8 of 9-mer MHC-I-bound antigens. Finally, we demonstrate that targeting reactive cysteines on MHC-I-bound antigens with a maleimide-conjugated Fc-binding cyclic peptide contributes to the induction of antibody-dependent cellular phagocytosis.

Abstract Currently, image recognition based on deep neural networks has become the mainstream direction of research; therefore, significant progress has been made in its application in the field of tea detection. Many deep models exhibit high recognition rates in tea leaves detection. However, deploying these models directly on tea-picking equipment in natural environments is impractical; the extremely high parameters and computational complexity of these models make it challenging to perform real-time tea leaves detection. Meanwhile, lightweight models struggle to achieve competitive detection accuracy; therefore, this paper addresses the issue of computational resource constraints in remote mountain areas and proposes Reconstructed Feature and Dual Distillation (RFDD) to enhance the detection capability of lightweight models for tea leaves. In our method, the Reconstructed Feature selectively masks the feature of the student model based on the spatial attention map of the teacher model; it utilizes a generation block to force the student model to generate the teacher’s full feature. The Dual Distillation comprises Decoupled Distillation and Global Distillation. Decoupled Distillation divides the reconstructed feature into foreground and background features based on the Ground-Truth. This compels the student model to allocate different attention to foreground and background, focusing on their critical pixels and channels. However, Decoupled Distillation leads to the loss of relation knowledge between foreground and background pixels. Therefore, we further perform Global Distillation to extract this lost knowledge. Since RFDD only requires loss calculation on feature map, it can be easily applied to various detectors. We conducted experiments on detectors with different frameworks, using a tea dataset collected at the Huangshan Houkui Tea Plantation. The experimental results indicate that, under the guidance of RFDD, the student detectors have achieved performance improvements to varying degrees. For instance, a one-stage detector like RetinaNet (ResNet-50) experienced a 3.14% increase in Average Precision (AP) after RFDD guidance. Similarly, a two-stage model like Faster RCNN (ResNet-50) obtained a 3.53% improvement in AP. This offers promising prospects for lightweight models to efficiently perform real-time tea leaves detection tasks.

Industrial waste, including wastewater and solid waste, often contains toxic heavy metals that necessitate extraction and separation prior to safe disposal or reusing them. Sewage sludge incineration ash (SSIA), a non-incinerable waste, holds significant amounts of heavy metals such as iron, zinc, copper, nickel, chromium, and lead. Recovery and reuse of heavy metals from SSIA and further application of treated SSIA sludge remain challenging. Ethylenediaminetetraacetic acid (EDTA) is widely used for heavy metals chelation in different applications. While its chelation with heavy metals is rapid and easy to achieve, the de-chelation of the metal complexes is otherwise slow (∼3 days) and challenging due to their high stability constants. In this study, we investigate the recovery of heavy metals from SSIA through chelation using EDTA, and develop, for the first time, a method to rapidly de-chelate the EDTA-metal complexes through the facile chilling process (1 – 3 h) that accelerates the separation of EDTA and metal ions. A sequential precipitation of high-purity heavy metals from the EDTA-metal complexes was demonstrated with and without de-chelation. This novel and versatile method allows the separation of many valuable compounds from the treated SSIA, including regenerated EDTA, potassium hexafluorosilicate, iron phosphate, iron(III) hydroxide, iron silicate, titanium phosphate, calcium phosphate, copper(I) thiocyanate, nickel bis(dimethylglyoximate), lead(II) sulfate, and zinc sulfide. This approach opens doors for more sustainable waste management and the recovery of valuable resources from industrial waste.

Abstract Knowledge distillation can transfer the knowledge from the pre-trained teacher model to the student model, thus effectively accomplishing model compression. Previous studies have carefully crafted knowledge representation, targeting loss function design, and distillation location selection, but there have been few studies on the role of classifiers in distillation. Previous experiences have shown that the final classifier of the model has an essential role in making inferences, so this paper attempts to narrow the gap in performance between models by having the student model directly use the classifier of the teacher model for the final inference, which requires an additional projector to help match features of the student encoder with the teacher's classifier. However, a single projector cannot fully align the features, and integrating multiple projectors may result in better performance. Considering the balance between projector size and performance, through experiments, we obtain the size of projectors for different network combinations and propose a simple method for projector integration. In this way, the student model undergoes feature projection and then uses the classifiers of the teacher model for inference, obtaining a similar performance to the teacher model. Through extensive experiments on the CIFAR-100 and Tiny-ImageNet datasets, we show that our approach applies to various teacher–student frameworks simply and effectively.

Soil bacterial α and β diversity patterns under nitrogen (N) addition have been intensively examined, but γ diversity patterns remain largely unknown, especially, the mechanisms that concurrently control changes in α, β and γ diversity remain elusive. Therefore, we formulated a conceptual framework that simultaneously considers candidate drivers including ubiquitous species, rare species, and community assembly processes to elucidate the driving mechanisms of α, β and γ diversity under N addition. The conceptual framework was tested by compiling the sequence data of seven studies published from January 1997 to May 2022 and following the same analysis as our own two long-term multilevel N addition experiments. We demonstrate that subtractive heterogenization based on environment selection simultaneously predicts the changes in α, β and γ diversity under long-term N addition. That is, long-term N addition led to the decline of ubiquitous species (subtractive processes) through low soil pH, and promoted the strength of heterogeneous selection (heterogeneous processes) via enhancing environmental heterogeneity, subsequently causing lower α diversity and γ diversity but higher β diversity. These results mean that N addition may lead to a significant loss of soil bacterial diversity around the world. Together, these findings offer a way to simultaneously predict soil bacterial α, β and γ diversity responses to the ongoing atmospheric nitrogen deposition.

BackgroundImbalance in intestinal microbiota caused by microbial species and proportions or metabolites derived from microbes are associated with hypertension, as well as diabetic nephropathy. However, the involvement of the intestinal microbiota and metabolites in hypertension and diabetic nephropathy comorbidities (HDN) remains to be elucidated.MethodsWe investigated the effects of intestinal microbiota on HDN in a rat model and determined the abundance of the intestinal microbiota using 16S rRNA sequencing. Changes in fecal and serum metabolites were analyzed using ultra-high-performance liquid chromatography-mass spectrometry.ResultsThe results showed abundance of Proteobacteria and Verrucomicrobia was substantially higher, whereas that of Bacteroidetes was significant lower in the HDN group than in the sham group. Akkermansia, Bacteroides, Blautia, Turicibacter, Lactobacillus, Romboutsia, and Fusicatenibacter were the most abundant, and Prevotella, Lachnospiraceae_NK4A136_group, and Prevotella_9 were the least abundant in the HDN group. Further analysis with bile acid metabolites in serum showed that Blautia was negatively correlated with taurochenodeoxycholic acid, taurocholic acid, positively correlated with cholic acid and glycocholic acid in serum.ConclusionsThese findings suggest that the gut microbiota and metabolites in feces and serum substantially differed between the HDN and sham groups. The F/B ratio was higher in the HDN group than in the sham group. Blautia is potentially associated with HDN that correlated with differentially expressed bile acid metabolites, which might regulate the pathogenesis of HDN via the microorganism–gut–metabolite axis.

After the decline of water transportation along the Grand Canal, the integration of urban development and the preservation of cultural heritage along the canal has become imperative. This paper takes the titled landscape as its research perspective and investigates the cultural significance of the canal through its historical, spatial, artistic, and spiritual dimensions, identifying the “Ten Canal Scenes” (TCS) that encapsulate both the canal’s heritage and the unique characteristics of Hangzhou, with the aim of establishing notable urban cultural landmarks. Archival analysis, average nearest neighbor (ANN) analysis, nuclear density analysis, and clustering of resource sites are first used to identify cultural landscape features. Evaluation and decision-making techniques are then used to comprehensively assess and categorize the conservation and utilization value for the TCS based on the value evaluation framework. Finally, it proposes strategies for enhancing the comprehensive values of titled landscapes and addressing socio-economic and cultural dimensions. These efforts seek to reconcile the preservation of the canal’s cultural heritage with the ongoing regeneration and development of the city and propose references for a localized canal development model based on titled landscapes.

As digital technologies and smart city development continue to grow, the threats of cybercrime and scams have become increasingly salient for city managers, businesses, and citizens worldwide. With a less effective data privacy protection, the number of new types of scams that precisely target victims is increasing. We collected 6,871 crawl fraud cases from news reports and local websites between October 2018 and December 2021 in Mainland China and Hong Kong. We generated 2,747 messages from news and open-source message datasets on GitHub. Based on these novel datasets, we conducted a comparative analysis of cyber telecom scams between Mainland China and Hong Kong and identified victim profiles using adata technology and target group index analysis. Furthermore, we developed a message-classifier scam alert model using data mining and machine learning algorithms. Our study provides valuable insights and essential implications on how data analytics can support future antifraud initiatives and help cities build safer urban hubs.

Abstract Sepsis, a life-threatening condition caused by an inflammatory response to systemic infection, results in a significant social burden and healthcare costs. This study aimed to investigate the relationship between the C-reactive protein (CRP) trajectories of patients with sepsis in the intensive care unit (ICU) and the in-hospital mortality rate. We reviewed 1464 patients with sepsis treated in the ICU of Dongyang People’s Hospital from 2010 to 2020 and used latent growth mixture modeling to divide the patients into four classes according to CRP trajectory (intermediate, gradually increasing, persistently high, and persistently low CRP levels). We found that patients with intermediate and persistently high CRP levels had the lowest (18.1%) and highest (32.6%) in-hospital mortality rates, respectively. Multiple logistic regression analysis showed that patients with persistently high (odds ratio [OR] = 2.19, 95% confidence interval [CI] = 1.55–3.11) and persistently low (OR = 1.41, 95% CI = 1.03–1.94) CRP levels had a higher risk of in-hospital mortality than patients with intermediate CRP levels. In conclusion, in-hospital mortality rates among patients with sepsis differ according to the CRP trajectory, with patients with intermediate CRP levels having the lowest mortality rate. Further research on the underlying mechanisms is warranted.

Since the COVID-19, cough sounds have been widely used for screening purposes. Intelligent analysis techniques have proven to be effective in detecting respiratory diseases. In 2021, there were up to 10 million TB-infected patients worldwide, with an annual growth rate of 4.5%. Most of the patients were from economically underdeveloped regions and countries. The PPD test, a common screening method in the community, has a sensitivity of as low as 77%. Although IGRA and Xpert MTB/RIF offer high specificity and sensitivity, their cost makes them less accessible. In this study, we proposed a feature fusion model-based cough sound classification method for primary TB screening in communities. Data were collected from hospitals using smart phones, including 230 cough sounds from 70 patients with TB and 226 cough sounds from 74 healthy subjects. We employed Bi-LSTM and Bi-GRU recurrent neural networks to analyze five traditional feature sets including the Mel frequency cepstrum coefficient (MFCC), zero-crossing rate (ZCR), short-time energy, root mean square, and chroma_cens. The incorporation of features extracted from the speech spectrogram by 2D convolution training into the Bi-LSTM model enhanced the classification results. With traditional futures, the best TB patient detection result was achieved with the Bi-LSTM model, with 93.99% accuracy, 93.93% specificity, and 92.39% sensitivity. When combined with a speech spectrogram, the classification results showed 96.33% accuracy, 94.99% specificity, and 98.13% sensitivity. Our findings underscore that traditional features and deep features have good complementarity when fused using Bi LSTM modelling, which outperforms existing PPD detection methods in terms of both efficiency and accuracy.

Abstract Although the classification method based on the deep neural network has achieved excellent results in classification tasks, it is difficult to apply to real-time scenarios because of high memory footprints and prohibitive inference times. Compared to unstructured pruning, structured pruning techniques can reduce the computation cost of the model runtime more effectively, but inevitably reduces the precision of the model. Traditional methods use fine tuning to restore model damage performance. However, there is still a large gap between the pruned model and the original one. In this paper, we use progressive multi-level distillation learning to compensate for the loss caused by pruning. Pre-pruning and post-pruning networks serve as the teacher and student networks. The proposed approach utilizes the complementary properties of structured pruning and knowledge distillation, which allows the pruned network to learn the intermediate and output representations of the teacher network, thus reducing the influence of the model subject to pruning. Experiments demonstrate that our approach performs better on CIFAR-10, CIFAR-100, and Tiny-ImageNet datasets with different pruning rates. For instance, GoogLeNet can achieve near lossless pruning on the CIFAR-10 dataset with 60% pruning. Moreover, this paper also proves that using the proposed distillation learning method during the pruning process achieves more significant performance gains than after completing the pruning.

ObjectivesThe aim is to evaluate the effect of a novel 14-day fasting regimen on the balance between skeletal muscle and adipose tissue composition which might associate with inflammatory factors. Our analysis includes basic physical examinations, clinical laboratory analysis, bioelectrical impedance and biochemical analytic assessments of healthy volunteers.MethodsEight healthy subjects were randomly selected from a pool of volunteers to undergo a continual dietary deprivation (CDD) regimen. Individuals were assigned to take Flexible Abrosia (FA, prebiotic combination) plus appropriate mineral supplement of potassium and magnesium at 3 mealtime every day to prevent potential injury from starved intestinal flora and avoid spasms of smooth muscle due to hunger. Physical and medical examinations were conducted and blood samples were collected at following timepoints: before CDD as self-control (0D), day 7 and day 14 during fasting, and 7-21days and/or 2~3mo after refeeding.ResultsThe combination of FA and mineral supplements significantly decreased self-reported physical response of starvation, with tolerable hunger-mediated sensations experienced during CDD. Bioelectrical and biochemical results indicated significant reduction in both muscle lean and fat mass on day 7. Meanwhile, markers related to fat composition consistently decreased during and after CDD. In addition, most biochemical marker levels, including serum proteins, reached their inflection points at the 7th day of CDD as compared to the control measurements. Levels of these factors started to show a relative plateau, or reversed direction upon the 14th day of CDD. The exceptions of above factors were myostatin and complement protein C3, which remained at lower concentrations in the blood throughout CDD, and were unable to fully recover toward baseline levels even after 3 months’ refeeding.ConclusionOur results indicated that human subjects undergoing prolonged dietary restriction were well protected by FA and mineral ions from gut injury or physical discomfort of starvation. Most factors showed a relative plateau response at the end of 14D-CDD. The muscle tissues were well preserved during prolonged fasting, and an improved protein/lipid ratio was observed. Upon refeeding, constant lower levels of myostatin and complement C3 were maintained after CDD implies a long-term beneficial effect in dealing with anti-aging and inflammation.

Laser welding of the near α-phase titanium alloy Ti-4Al-2V, used for complex components in the nuclear industry, has been rarely reported. In this study, butt weld joints made of Ti-4Al-2V alloy plates under different parameters, including the laser power, the welding speed, and the defocus distance, were manufactured and analyzed. The results showed that adjusting the combination of 4.2 kW of laser power, a 20 mm/s welding speed, and a −2 mm defocus distance could achieve a penetration depth exceeding 6 mm. Porosity defects were prone to forming in the middle and bottom parts of the fusion zone, due to rapid cooling. The microstructure of the fusion zone was mainly needle-like α martensite, which precipitated in the form of specific clusters. The interior of a cluster was composed of three types of variants with /60° phase interfaces to achieve the lower boundary’s energy. Affected by the microstructure and welding defects, the strength of the weld joint was basically similar under different welding conditions, namely about 720 MPa, slightly higher than that of the base metal, while the rupture elongation at breaking decreased by more than 50%. The micro-Vickers hardness of the weld joints was about 50–60 HV higher than that of the base metal, while the impact toughness was about 40 KJ, almost half that of the base metal. This research lays a solid foundation for the engineering application of laser welding of Ti-4Al-2V alloys.

DC power line communication (PLC) technique has been proven to be efficient for single-core cable communication and DC power supplies. However, the effect of high temperature will have a great influence on the performance of DC-PLC for downhole applications. In this paper, a high-temperature DC-PLC system that enables the operation to 150 °C is presented for long-term downhole production monitoring. Based on the DC-PLC techniques, the downhole system with single-core cable for long-term oil production monitoring and controlling is investigated. In order to improve the transmission efficiency, an adaptive PLC decoding algorithm is proposed to accommodate the single-core cables due to the long-term effect of high temperature, high pressure as well as vibration of the bad downhole conditions. Moreover, a current feedback amplifier LTC1210X of ANALOG DEVICES with extreme high-temperature operation is used as the single-core cable driver for data transmission. Finally, field experiments were conducted, and the results demonstrate the effectiveness of the proposed high-temperature DC-PLC system for the improvement of the efficiency and stability of the downhole system.

Considerable evidence shows that oxidative stress exists in the pathophysiological process of female reproductive system diseases. At present, there have been many studies on oxidative stress of placenta during pregnancy, especially for preeclampsia. However, studies that directly focus on the effects of oxidative stress on blood vessels at the maternal-fetal interface and their associated possible outcomes are still incomplete and ambiguous. To provide an option for early clinical prediction and therapeutic application of oxidative stress in female reproductive system diseases, this paper briefly describes the composition of the maternal-fetal interface and the molecular mediators produced by oxidative stress, focuses on the sources of oxidative stress and the signaling pathways of oxidative stress at the maternal-fetal interface, expounds the adverse consequences of oxidative stress on blood vessels, and deeply discusses the relationship between oxidative stress and some pregnancy complications and other female reproductive system diseases.

BackgroundDirect antihypertensive therapy in hypertensive patients with a high CVD risk can reduce the incidence of cardiovascular death but increase adverse cardiovascular events, so additional ways to identify hypertensive patients at high risk may be needed. Studies have shown that immunity and inflammation affect the prognoses of patients with hypertension and that the pan-immune-inflammation value (PIV) is an index to assess immunity and inflammation, but few studies have applied the PIV index to patients with hypertension.ObjectiveTo explore the relationship between the PIV and long-term all-cause and cardiovascular mortality in patients with hypertension.MethodData from the National Health and Nutrition Examination Survey (NHANES) 1999–2018 with a mortality follow-up through December 31, 2019, were analyzed. A total of 26,781 participants were evaluated. The patients were grouped based on PIV levels as follows: T1 group (n = 8,938), T2 group (n = 8,893), and T3 group (n = 8,950). The relationship between the PIV and long-term all-cause and cardiovascular death was assessed by survival curves and Cox regression analysis based on the NHANES recommended weights.ResultThe PIV was significantly associated with long-term all-cause and cardiovascular mortality in patients with hypertension. After full adjustment, patients with higher PIV have a higher risk of all-cause [Group 3: HR: 1.37, 95% CI: 1.20–1.55, p

BackgroundLiposarcomas (LPS) are mesenchymal malignancies with four principal subtypes presenting distinct molecular and clinical features. Pleomorphic liposarcoma (PLPS) is one of the rarest and most aggressive subtypes of LPS. Surgical resection is currently a preferred curative approach for localized PLPS. However, the prognosis of unresectable PLPS is extremely poor, and there is no standard treatment.Case presentationA 59-year-old Chinese woman was diagnosed with unresectable PLPS. The case was discussed and managed by specialists from a multidisciplinary team at Fudan Zhongshan Hospital. Preoperative radiotherapy (RT) of intensity-modulated radiation therapy (IMRT) at 50 Gy/25 Fx concurrently with the angiogenesis inhibitor anlotinib (8 mg, days 1–14, every 3 weeks) was prescribed to the patient. The dosage of anlotinib was increased to 10 mg after RT. After 6 months of treatment, the tumor had significantly shrunk and was successfully resected. Examination of the surgical specimens showed a pathological complete response (pCR). Until the latest follow-up (April 2022), no recurrence was observed, and disease-free survival has exceeded 14 months.ConclusionThis case sheds light on the probability that perioperative RT combined with an angiogenesis inhibitor can be effectively used in PLPS, which is resistant to chemotherapy and usually considered to have a poor prognosis. Further studies with randomized controlled clinical trials will improve our knowledge of this preoperative treatment strategy.

Gastric cancer (GC) is the fifth most commonly diagnosed cancer and usually has a dismal prognosis. Our previous study highlights the contribution of focal adhesion kinase (FAK) in the tumorigenesis of diffuse gastric cancer (DGC), a subtype of GC according to Lauren classification. The prognostic value of phosphorylated FAK (pFAK) in GC remains to be explored. To explore the prognostic value of pFAK, we retrospectively collected 176 formalin-fixed paraffin-embedded (FFPE) tumor tissues from GC patients who underwent D2 gastrectomy without neoadjuvant treatment. The immunohistochemistry (IHC) staining of pFAK was performed. Survival analysis was performed by Kaplan–Meier and risk factors were evaluated by Cox regression analysis. A pFAK-based nomogram was also constructed for the prediction of overall survival (OS). We demonstrated that the prognosis of pFAK-positive patients was worse than that of the pFAK-negative patients in GC (p = 0.010; hazard ratio [HR] = 1.777, 95% CI 1.131 to 2.791; median OS, 46.6 vs. 86.3 months, respectively), and positive pFAK was also an independent risk factor for the worse prognosis of GC (p = 0.0054; HR = 1.89, 95% CI 1.21–2.96). Moreover, the nomogram based on pFAK and other independent risk factors could improve predictive accuracy for prognosis of GC. In conclusion, through analysis of a large collection of clinically annotated GC samples, we demonstrate that pFAK is a negative prognostic factor in GC, and a nomogram integrating pFAK could help predict OS for GC patients.

Malabar spinach (Basella alba), amaranth (Amaranthus tricolor), and sweet potato (Ipomoea batatas) are leafy vegetables found in Southwest China. The variation of chlorophyll, carotenoids, ascorbic acid, total flavonoids, phenolic compounds, and antioxidant capacity was studied in the leaves and stems of the three vegetables. The content of main health-promoting compounds and the antioxidant capacity in the leaves were higher than that in the stems, indicating that the leaves of the three vegetables possess greater nutritional value. The trend of total flavonoids in all three vegetables was similar to the trend of antioxidant capacity, suggesting that the total flavonoids may be the major antioxidants wihin these vegetables. Eight individual phenolic compounds were detected in three different vegetables. The most abundant levels of individual phenolic compounds in the leaves and stems of malabar spinach, amaranth, and sweet potato were 6′-O-feruloyl-d-sucrose (9.04 and 2.03 mg g−1 DW), hydroxyferulic acid (10.14 and 0.73 mg g−1 DW), and isorhamnetin-7-O-glucoside (34.93 and 6.76 mg g−1 DW), respectively. Sweet potato exhibited a higher total and individual phenolic compound content compared to malabar spinach and amaranth. Overall, the results demonstrate that the three leafy vegetables possess high nutritional value, and could be used not only for consumption but also in various other fields, including medicine and chemistry.

The discovery of kisspeptin as a critical central regulatory factor of GnRH release has given people a novel understanding of the neuroendocrine regulation in human reproduction. Kisspeptin activates the signaling pathway by binding to its receptor kisspeptin receptor (KISS1R) to promote GnRH secretion, thereby regulating the hypothalamic-pituitary-gonadal axis (HPG) axis. Recent studies have shown that kisspeptin neurons located in arcuate nucleus (ARC) co-express neurokinin B (NKB) and dynorphin (Dyn). Such neurons are called KNDy neurons. KNDy neurons participate in the positive and negative feedback of estrogen to GnRH secretion. In addition, kisspeptin is a key factor in the initiation of puberty, and also regulates the processes of female follicle development, oocyte maturation, and ovulation through the HPG axis. In male reproduction, kisspeptin also plays an important role, getting involved in the regulation of Leydig cells, spermatogenesis, sperm functions and reproductive behaviors. Mutations in the KISS1 gene or disorders of the kisspeptin/KISS1R system may lead to clinical symptoms such as idiopathic hypogonadotropic hypogonadism (iHH), central precocious puberty (CPP) and female infertility. Understanding the influence of kisspeptin on the reproductive axis and related mechanisms will help the future application of kisspeptin in disease diagnosis and treatment. In this review, we critically appraise the role of kisspeptin in the HPG axis, including its signaling pathways, negative and positive feedback mechanisms, and its control on female and male reproduction.

Abstract Background Treating patients with advanced sarcomas is challenging due to great histologic diversity among its subtypes. Leiomyosarcoma (LMS) and de-differentiated liposarcoma (DDLPS) are two common and aggressive subtypes of soft tissue sarcoma (STS). They differ significantly in histology and clinical behaviors. However, the molecular driving force behind the difference is unclear. Methods We collected 20 LMS and 12 DDLPS samples and performed whole exome sequencing (WES) to obtain their somatic mutation profiles. We also performed RNA-Seq to analyze the transcriptomes of 8 each of the LMS and DDLPS samples and obtained information about differential gene expression, pathway enrichment, immune cell infiltration in tumor microenvironment, and chromosomal rearrangement including gene fusions. Selected gene fusion events from the RNA-seq prediction were checked by RT-PCR in tandem with Sanger sequencing. Results We detected loss of function mutation and deletion of tumor suppressors mostly in LMS, and oncogene amplification mostly in DDLPS. A focal amplification affecting chromosome 12q13–15 region which encodes MDM2, CDK4 and HMGA2 is notable in DDLPS. Mutations in TP53, ATRX, PTEN, and RB1 are identified in LMS but not DDLPS, while mutation of HERC2 is only identified in DDLPS but not LMS. RNA-seq revealed overexpression of MDM2, CDK4 and HMGA2 in DDLPS and down-regulation of TP53 and RB1 in LMS. It also detected more fusion events in DDLPS than LMS (4.5 vs. 1, p = 0.0195), and the ones involving chromosome 12 in DDLPS stand out. RT-PCR and Sanger sequencing verified the majority of the fusion events in DDLPS but only one event in LMS selected to be tested. The tumor microenvironmental signatures are highly correlated with histologic types. DDLPS has more endothelial cells and fibroblasts content than LMS. Conclusions Our analysis revealed different recurrent genetic variations in LMS and DDLPS including simultaneous upregulation of gene expression and gene copy number amplification of MDM2 and CDK4. Up-regulation of tumor related genes is favored in DDLPS, while loss of suppressor function is favored in LMS. DDLPS harbors more frequent fusion events which can generate neoepitopes and potentially targeted by personalized immune treatment.

Abstract Background The aim of this study was to explore the utility of circulating free DNA (cfDNA) in the evaluation of clinical tumor burden and survival in Chinese patients with metastatic colorectal cancer (mCRC) and to preliminarily summarize some metastatic characteristics associated with mutational status. Methods A panel covering a total of 197 hotspot mutations of KRAS, NRAS, BRAF and PIK3CA was used to evaluate the mutational status in plasma by next-generation sequencing (NGS) technology in 126 patients with mCRC. An amplification-refractory mutation system (ARMS) was used to analyze genomic DNA from matched tissue samples. Clinical markers including carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199), carbohydrate antigen 125 (CA125), neuron-specific enolase (NSE) and lactate dehydrogenase (LDH) in serum and the sum of all tumor diameters on CT or PET/CT were collected to indicate clinical tumor burden. The correlations between cfDNA and clinical tumor burden were analyzed using Pearson correlation and linear regression models. The median progression-free survival (PFS) and 1-year overall survival (OS) rates were calculated by Kaplan-Meier (K-M) survival analysis. Results Of the 126 enrolled patients, patients who were tested positive for mutations in plasma accounted for 45.2% (57/126). Mutations in KRAS, NRAS, BRAF and PIK3CA were detected in 37.3% (47/126), 1.6% (2/126), 3.2% (4/126) and 13.5% (17/126) of patients, respectively. The overall concordance rate of mutational status between plasma and matched tissues was 78.6% (99/126). Sixteen patients had mutations in plasma that were not detected in tissue, including some rare hotspot mutations. The cfDNA concentration was significantly correlated with the levels of clinical markers, especially CEA (P 17.91 ng/ml) had shorter median progression-free survival (6.6 versus 11.7 months, P

Human skin functions as a physical barrier, preventing the entry of foreign pathogens while also accommodating a myriad of commensal microorganisms. A key contributor to the skin landscape is the sebaceous gland. Mice devoid of sebocytes are prone to skin infection, yet our understanding of how sebocytes function in host defense is incomplete. Here, we show that the small proline-rich proteins, SPRR1 and SPRR2 are bactericidal in skin. SPRR1B and SPPR2A were induced in human sebocytes by exposure to the bacterial cell wall component lipopolysaccharide (LPS). Colonization of germ-free mice was insufficient to trigger increased SPRR expression in mouse skin, but LPS injected into mouse skin stimulated increased expression of the mouse SPRR orthologous genes, Sprr1a and Sprr2a, through activation of MYD88. Both mouse and human SPRR proteins displayed potent bactericidal activity against MRSA (methicillin-resistant Staphylococcus aureus), Pseudomonas aeruginosa, and skin commensals. Thus, Sprr1a−/−;Sprr2a−/− mice are more susceptible to MRSA and P. aeruginosa skin infection. Lastly, mechanistic studies demonstrate that SPRR proteins exert their bactericidal activity through binding and disruption of the bacterial membrane. Taken together, these findings provide insight into the regulation and antimicrobial function of SPRR proteins in skin and how the skin defends the host against systemic infection.

BackgroundLeiomyosarcoma (LMS) is a malignant smooth muscle neoplasm, in which the efficacy of immune checkpoint blockade (ICB) is very limited. What is worse, loss of PTEN, known as a negative factor for ICB, frequently occurred in LMS. Seeking new strategies for LMS patients harboring loss of PTEN is important and challenging.Case PresentationA 42-year-old Chinese male was diagnosed as having unresectable LMS of the iliopsoas. After the failure of two prior chemotherapy regimens, whole-exome sequencing revealed that tumor tissue had high tumor mutation burden (689 Muts), high microsatellite instability, and some somatic mutations, including PTEN (copy number loss and p.N323fs), MSH6 (p.F1088fs), TP53 p.R273C, ASXL1 p.G645fs, ATR p.S1843P, and CDKN2A p.A118P. Then, antiangiogenic agent (pazopanib or anlotinib) plus pembrolizumab was administered from January 2 to August 6, 2018. However, pazopanib was stopped on June 18 due to the grade 2/3 adverse effect of hand–foot skin reaction, and anlotinib was administered. Considering that the tumor shrunk after immunotherapy, he underwent radical resection on September 6, 2018. The final pathological diagnosis confirmed pathologic complete response (CR). Until the latest follow-up (September 15, 2021), no progressive disease was observed and total disease-free survival has exceeded 36 months.ConclusionWe presented a patient with an unresectable mismatch repair (MMR)-deficient LMS harboring biallelic loss of PTEN who achieved CR from a combination strategy of antiangiogenesis plus pembrolizumab. Such a strategy might be a promising strategy to overcome the ICB resistance caused by the loss of PTEN. Such conclusions need to be further confirmed in further investigations.

Purpose: Cyclin D1 has been identified as a proto-oncogene associated with the uncontrolled proliferation of tumor cells. This systematic review and meta-analysis aims to estimate the prognostic significance of cyclin D1 in multiple myeloma (MM) patients. Method: We searched for qualified data in PubMed, Embase, and Web of Science up to February 2020. Data quality was assessed by the Newcastle-Ottawa scale (NOS). Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were used to evaluate the relationship between cyclin D1 expression and overall survival (OS), progression-free survival (PFS)/event-free survival (EFS) in patients with MM. Result: A total of 13 studies involving 961 patients were included. Overall, pooled analysis revealed significant heterogeneity between cyclin D1 expression and the prognosis of MM (OS, HR = 1.08, 95% CI: 0.71-1.64, I 2 = 67.9%; PFS/EFS, HR = 0.97, 95% CI: 0.49-1.93, I 2 = 85.8%). Subgroup analysis revealed that the prolongation of OS was relevant to increased expression of cyclin D1 in MM patients in the relapsed and refractory group (OS, HR = 0.46, 95% CI: 0.24-0.90). Another subgroup assessment of OS established that MM patients with CCND1 overexpression in the bortezomib group had longer survival time (HR = 0.30, 95% CI: 0.11-0.82), whereas, those overexpressing CCND1 in the conventional chemotherapy group had poor prognosis (HR = 2.19, 95% CI: 1.18-4.08). We also found that increased cyclin D1 expression correlated favorably with PFS in the autologous stem cell transplantation (ASCT) (HR = 0.45, 95% CI: 0.28-0.73) or reverse transcription-polymerase chain reaction (RT-PCR) group (HR = 0.41, 95% CI: 0.26-0.64). Conclusion: The result of this meta-analysis suggested that CCND1 overexpression might be a predictive biomarker for MM patients when treated with bortezomib, receiving ASCT, or in relapsed and refractory period.

This paper proposes a data anomaly detection and correction algorithm for the tea plantation IoT system based on deep learning, aiming at the multi-cause and multi-feature characteristics of abnormal data. The algorithm is based on the Z-score standardization of the original data and the determination of sliding window size according to the sampling frequency. First, we construct a convolutional neural network (CNN) model to extract abnormal data. Second, based on the support vector machine (SVM) algorithm, the Gaussian radial basis function (RBF) and one-to-one (OVO) multiclassification method are used to classify the abnormal data. Then, after extracting the time points of abnormal data, a long short-term memory network is established for prediction with multifactor historical data. The predicted values are used to replace and correct the abnormal data. When multiple consecutive abnormal values are detected, a faulty sensor judgment is given, and the specific faulty sensor location is output. The results show that the accuracy rate and micro-specificity of abnormal data detection for the CNN-SVM model are 3–4% and 20–30% higher than those of the traditional CNN model, respectively. The anomaly detection and correction algorithm for tea plantation data established in this paper provides accurate performance.

Background: Our previous study showed that CXCL11 could play an immunomodulatory role. In this study, we investigated the regulator (miR-205–3p) of CXCL11 and the mechanism of miR-205–3p as a tumor suppressor gene in gastric cancer (GC). Materials and methods: A target relationship between miR-205–3p and CXCL11 was revealed by using the bioinformatics method. This study detected the expressions of miR-205–3p and CXCL11 through qRT-PCR and Western blotting. Moreover, the expressions of Akt, PD-L1, p16, p21, and senescence-associated secretory phenotype (SASP) factor were determined. The effects of miR-205 on proliferation, invasion, and senescence of GC cells were assessed by using methods, such as transfection, Transwell assay, tablet cloning, flow cytometry, and senescence-associated beta-galactosidase (SA-β-gal) staining. Furthermore, the effects were verified using methods, like immunohistochemistry, flow cytometry and SA-β-gal in animal experiments. Results: Based on the study, it is found that the expression of miR-205–3p is down-regulated, while that of CXCL11 is up-regulated in GC cell lines. By regulating CXCL11, miR-205–3p inhibits Akt activation, reduces the proliferation and invasion of GC cells, promotes cell apoptosis, induces senescence of GC cells, and secretes immunostimulatory SASP factor. The animal experiments confirm that miR-205–3p promotes cell senescence, down-regulates the immunosuppressive signal induced by PD-L1, and promotes secretion of immunostimulatory SASP factor, so that more T cells are recruited in blood and tumors. Conclusions: This study revealed the molecular mechanism of miR-205–3p in inhibiting proliferation and invasion and inducing senescence of GC cells by regulating CXCL11 and Akt pathways in animal and cell experiments.

Background: Immune checkpoint inhibitors (ICIs) are employed to treat various cancers, including soft tissue sarcomas (STSs), and less than 20% of patients benefit from this treatment. Vascular endothelial growth factor (VEGF) promotes the immunosuppressive tumor microenvironment and contributes to ICI-resistant therapy. Anti-VEGF receptor tyrosine-kinase inhibitors (TKIs) combined with ICIs have shown antitumor activity in patients with alveolar soft-part sarcoma (ASPS). However, they have not been extensively studied to treat other STS subtypes, such as leiomyosarcoma (LMS), dedifferentiated liposarcoma (DDLPS), undifferentiated pleomorphic sarcoma (UPS), myxofibrosarcoma (MFS), and angiosarcoma (AS).Methods: In this retrospective study, we collected data from 61 patients who were diagnosed with advanced STS based on imaging and histology, including LMS, DDLPS, and UPS. Among them, 41 patients were treated with ICIs combined with TKIs and 20 patients received ICI therapy. The endpoints of progression-free survival (PFS) and overall response rate (ORR) were analyzed in the two groups, and the overall response [partial response (PR), stable disease (SD), and progressive disease (PD)] of each patient was determined using RECIST 1.1 evaluation criteria.Results: In total, 61 STS patients had the following subtypes: LMS (n = 20), DDLPS (n = 17), UPS (n = 8), ASPS (n = 7), MFS (n = 7), and AS (n = 2). The median PFS (mPFS) was significantly prolonged after ICI treatment in combination with TKIs (11.74 months, 95% CI 4.41–14.00) compared to ICI treatment alone (6.81 months, 95% CI 5.43–NA) (HR 0.5464, p = 0.043). The 12-month PFS rates of patients who received ICI–TKI treatment were increased from 20.26% (95% CI 0.08–0.53) to 42.90% (95% CI 0.27–0.68). In the combination therapy group, 12 patients (30%) achieved PR, 25 patients (62.5%) achieved SD, and 3 patients (7.5%) achieved PD for 3 months or longer. In the non-TKI-combination group, 2 patients (9.5%) achieved PR, 14 patients (66.7%) achieved SD, and 5 patients (23.8%) achieved PD within 3 months. The ORRs in the two groups were 30.0% (ICI–TKI combination) and 9.5% (ICI only), respectively. A notable ORR was observed in the ICI–TKI combination group, especially for subtypes ASPS (66.7%), MFS (42.9%), and UPS (33.3%). The PD-L1 expression (n = 33) and tumor mutation burden (TMB, n = 27) were determined for each patient. However, our results showed no significant difference in PFS or response rates between the two groups.Conclusion: This study suggests that ICI–TKI treatment has antitumor activity in patients with STS, particularly the ASPS and MFS subtypes. Moreover, effective biomarkers to predict clinical outcomes are urgently needed after combination therapy in the STS subtypes.

Liposarcoma (LPS) is a rare and heterogeneous malignancy of adipocytic origin. Well-differentiated liposarcoma (WDLPS) and dedifferentiated liposarcoma (DDLPS) are two of the most common subtypes, showing similar genetic characterizations but distinct biological behaviors and clinical prognosis. Compared to WDLPS, DDLPS is more aggressive and has the potential of metastasis, as the malignant adipocytic tumor’s metabolic changes may have taken place during the tumorigenesis of LPSs. Therefore, to investigate the lipid alterations between the two subtypes, high-resolution liquid chromatography tandem mass spectrometry (LC-MS/MS) based untargeted lipidomic analysis was performed onto LPS tissues from 6 WDLPS and 7 DDLPS patients. The lipidomic analysis showed the upregulated phosphatidylcholines and phosphoethanolamines in DDLPS, and the upregulated triglycerides and diglycerides in WDLPS, which might be due to the uncompleted adipocytic dedifferentiation leading to such tumorigenesis. Such a finding was also confirmed by the similarity comparison of two LPS subtypes to the transcriptome of stromal vascular fraction at different differentiation stages. Transcriptomic analysis also demonstrated that metabolic pathways including the pentose phosphate pathway (PPP) were upregulated in WDLPS compared to DDLPS. Therefore, the cell line LPS853 was treated with the PPP inhibitor 6-aminonicotinamide ex vivo and the proliferation and invasion of LPS853 was significantly promoted by PPP inhibition, suggesting the potential role of PPP in the development and differentiation of LPS. In conclusion, this study described the altered lipid profiles of WDLPS and DDLPS for the first time, revealing the different differentiation stages of the two subtypes and providing a potential metabolic target for LPS treatment.

Human epididymitis is mainly caused by retrograde urinary tract infection with uropathogenic Escherichia coli (UPEC). This disease is an important factor (accounting for 20–30%) causing male infertility. C-type natriuretic peptide (CNP), a protein composed of 22 amino acids, is proved to play an immunoregulatory role in respiratory and cardiovascular systems. CNP is expressed extremely high in the epididymis, but whether CNP plays the same role in acute epididymitis is unclear. At first, we established an acute caput epididymitis model in rats with UPEC and treated them with CNP to measure inflammatory damage. Then RNA-seq transcriptome technology was used to reveal potential signal pathways. Secondly, the turbidity and activity of UPEC were assessed using a microplate reader and the amount of UPEC by agar plates after incubation with CNP. Thirdly, macrophages in caput epididymis were tested by immunohistochemistry (IHC). Meanwhile, lipopolysaccharide (LPS) with or without CNP was used to stimulate the macrophage (RAW264.7) in vitro and to detect the expression level of pro-inflammatory factors. Finally, the macrophage (RAW264.7) was treated with CNP, 8-Br-cGMP [cyclic guanosinc monophosphate (cGMP) analog] and KT5823 [protein kinase G (PKG) inhibitor], and the expression level of nuclear factor-k-gene binding (NF-kB) signal pathway was examined. The results showed that the damage of epididymis induced by UPEC as well as the pro-inflammatory factors could be alleviated significantly with CNP treatment. CNP could inhibit the activity and numbers of bacteria in both in vivo and in vitro experiments. Moreover, CNP repressed the invasion, and the expression of pro-inflammatory factors (such as NF-kB, IL-1β, IL-6, TNF-α) in macrophages and its effect could be inhibited by KT5823. Therefore, we drew a conclusion from the above experiments that CNP alleviates the acute epididymitis injury induced by UPEC. On one hand, CNP could inhibit the growth of UPEC. On the other hand, CNP could decrease invasion and inflammatory reaction of macrophages; the mechanism was involved in inhibiting NF-kB signal pathway through the cGMP/PKG in macrophages. This research would open up the possibility of using CNP as a potential treatment for epididymitis.

Abstract Background We aimed to investigate the correlation of Circ-SMARCA5 with disease severity and prognosis in multiple myeloma (MM), and its underlying mechanisms in regulating cell proliferation and apoptosis. Methods Bone marrow samples from 105 MM patients and 36 healthy controls were collected for Circ-SMARCA5 expression measurement. And the correlation of Circ-SMARCA5 expression with patients’ characteristics and survival was determined. In vitro, the effect of Circ-SMARCA5 on MM cell proliferation and apoptosis was evaluated by altering Circ-SMARCA5 expression through transfection. Rescue experiments and luciferase assay were further performed to explore the mechanism of Circ-SMARCA5 as well as its potential target miR-767-5p in regulating MM cell activity. Results Circ-AMARCA5 was downregulated in MM and presented a good value in distinguishing MM patients from controls and it was also negatively correlated with Beta-2-microglobulin (β2-MG) level and International Staging System (ISS) stage. Additionally, Circ-SMARCA5 high expression was associated with higher CR as well as better PFS and OS. As for in vitro experiments, Circ-SMARCA5 expression was lower in MM cell lines compared with normal cells, and Circ-SMARCA5 overexpression inhibited cell proliferation but promoted cell apoptosis in RPMI8226 cells. Rescue experiments disclosed that the effect of Circ-SMARCA5 on cell activity was attenuated by miR-767-5p, and luciferase reporter assay revealed direct binding between Circ-SMARCA5 and miR-767-5p. Conclusions Circ-SMARCA5 is downregulated and correlated with lower β2-MG level and ISS stage as well as better prognosis in MM patients, and it inhibits proliferation but promotes apoptosis of MM cells via directly sponging miR-767-5p.

Suspended sediment concentration (SSC) is an important indicator of water quality that affects the biological processes of river ecosystems and the evolution of floodplains and river channels. The in situ SSC measurements are costly, laborious and spatially discontinuous, while the spaceborne SSC overcome these drawbacks and becomes an effective supplement for in situ observation. However, the spaceborne SSC observations of rivers are more challenging than those of lakes and reservoirs due to their narrow widths and the broad range of SSCs, among other factors. We developed a novel SSC retrieval method that is suitable for the rivers. Water was classified as clear or turbid based on the Forel–Ule index, and optimal SSC models were constructed based on the spectral responses to SSCs in cases of different turbidity. The estimated SSC had a strong correspondence with in situ measurements, with a root mean squared error (RMSE) of 24.87 mg/L and a mean relative error (MRE) of 51.91%. Satellite-derived SSC showed good consistency with SSCs obtained from gauging stations (r2 > 0.79). We studied the spatiotemporal variation in SSC in the Yangtze main stream from 2017 to 2021. It increased considerably from May to October each year, with the peak generally occurring in July or August (ca. 200–300 mg/L in a normal year and 800–1000 mg/L in a flood year), while it remained stable and decreased to around 50 mg/L from November to April of the following year. It was high in the east and low in the west, with local maxima in Chongqing (ca. 80–150 mg/L) and in the lower Dongting Lake reaches (ca. 80–100 mg/L) and a local minima in the downstream of the Three Gorges Dam (ca. 1–20 mg/L). Case studies in the Yibin reach and Three Gorges Reservoir determined that local variation in SSCs is due to special hydrodynamic conditions and anthropogenic activities. The procedure applied to process Sentinel-2 imagery and the novel SSC retrieval method we developed supplement the deficiencies in river SSC retrieval.

This study investigated the effects of blanching and subsequent long-term frozen storage on the retention of health-promoting compounds and antioxidant capacity in frozen lateral buds of baby mustard. Results showed that all glucosinolates were well preserved during frozen storage, and 72.48% of total glucosinolate content was retained in the unblanched treatment group after 8 months, as were chlorophylls, carotenoids, ascorbic acid, total phenolics, soluble sugars, soluble proteins, and antioxidant capacity. The loss of nutritional qualities mainly occurred in the 1st month of frozen storage, and nutritional qualities in the unblanched treatment group were significantly better than those in the blanched treatment group during frozen storage. Blanching before freezing reduced contents of high-content glucosinolates and ascorbic acid, as well as antioxidant capacity levels. Therefore, we recommend using long-term frozen storage to preserve the quality of baby mustard to achieve annual supply, and freezing without blanching.

The heating, ventilation, and air conditioning (HVAC) system is a major energy consumer in office buildings, and its operation is critical for indoor thermal comfort. While previous studies have indicated that reinforcement learning control can improve HVAC energy efficiency, they did not provide enough information about end-to-end control (i.e., from raw observations to ready-to-implement control signals) for centralized HVAC systems in multizone buildings due to the limitations of reinforcement learning methods or the test buildings being single zones with independent HVAC systems. This study developed a model-free end-to-end dynamic HVAC control method based on a recently proposed deep reinforcement learning framework to control the centralized HVAC system of a multizone office building. By using the deep neural network, the proposed control method could directly take measurable parameters, including weather and indoor environment conditions, as inputs and control indoor temperature setpoints at a supervisory level. In some test cases, the proposed control method could successfully learn a dynamic control policy to reduce HVAC energy consumption by 12.8% compared with the baseline case using conventional control methods, without compromising thermal comfort. However, an over-fitting problem was noted, indicating that future work should first focus on the generalization of deep reinforcement learning.

Mammalian ovaries consist of follicles as basic functional units. Each follicle comprised an innermost oocyte and several surrounding flattened granulosa cells. Unlike males, according to the initial size of the primordial follicle pool and the rate of its activation and depletion, a female’s reproductive life has been determined early in life. Primordial follicles, once activated, will get into an irreversible process of development. Most follicles undergo atretic degeneration, and only a few of them could mature and ovulate. Although there are a lot of researches contributing to exploring the activation of primordial follicles, little is known about its underlying mechanisms. Thus, in this review, we collected the latest papers and summarized the signaling pathways as well as some factors involved in the activation of primordial follicles, hoping to lead to a more profound understanding of the cellular and molecular mechanisms of primordial follicle activation.

Objectives: The aim of this study was to evaluate a total fasting regimen assisted by a novel prebiotic, Flexible Abrosia (FA), in more than 7 days of continual dietary deprivation (7D-CDD). Our analysis included basic physical examinations, bioelectrical impedance analysis, and clinical lab and ELISA analysis in normal volunteers.Methods: Seven healthy subjects with normal body weight participated in 7D-CDD with the assistance of a specially designed probiotic. Individuals were assigned to take FA (113.4 KJ/10 g) at each mealtime to avoid possible injuries to intestinal flora and smooth the hunger sensation. During 7D-CDD, the subjects were advised to avoid any food intake, especially carbohydrates, except for drinking plentiful amounts of water. The examination samples were collected before CDD as self-control, at 7 days fasting, and after 7~14 days of refeeding. Three subjects were also tested after 6-m refeeding.Results: The FA-CDD regimen significantly decreased suffering from starvation, with tolerable hunger sensations during the treatment. With the addition of daily mineral electrolytes, the subjects not only passed through the entire 7D-CDD regimen but also succeed in 12~13 days total fasting in two subjects. There was a significant reduction in blood glucose, insulin, and high-density lipoprotein levels during fasting, and the blood concentrations of uric acid (UA), alanine aminotransferase (ALT), and creatine kinase (CK) were increased. However, after more than 2 months of refeeding, the disease markers ALT, GOT, and CK either remained stable or were slightly downregulated compared to their initial D0 control level.Conclusion: Our experiment has supplied the first positive evidence that, with the assistance of a daily nutritional supply of around 100 kcal total calories to their intestinal flora, human subjects were able to tolerate hunger sensations. We have found that, although 7D-CDD induced increases in UA, CK, and transferases during fasting, refeeding led the markers to become either down-regulated or unchanged compared to their initial levels. This phenomenon was further confirmed in longer-term (6 m) recovery. Our results failed to support the hypothesis that fasting induced liver damage, since ALT, GOT, and CK remained low after longer-term refeeding. Our findings indicate that the 7D-CDD regimen might be practical and that it might be valuable to design larger clinical fasting trials for improvement of health strategy-targeting in metabolic disorders.

Abstract To satisfy the rapidly growing requirements of wireless data services recently, fog computing which is as an extension of cloud computing is proposed for offloading the Internet of Things (IoT) data services and applications. It depends more on the collaboration of near-located devices, instead of sending the information to remote servers. In this paper, we conceive the idea of utilizing device-to-device (D2D) communications as the infrastructures for computation and communication. In particular, D2D communication technology is one of the most important and innovative revolutions in the development of future cellular networks, which greatly enlarges the system capacity and extensively enriches the service category and application diversity. In computation part, by analyzing the interest difference of users, a Virtual Fog Community (VFC) is established in this paper, which exploits the coalition game based on the transfer effectiveness to adaptively divide users into multiple fog communities. In communication part, by perceiving the importance degrees of users and accordingly employing multidimensional network status parameters such as the local centrality and closeness degree, the best cooperative user can be reasonably selected based on the physical and social attributes of users. Therefore, the corresponding inter-community and intra-community D2D cooperative transmission mechanisms are devised to dramatically optimize the network resource utilization. Simulation results show that the proposed mechanism fully exploits the social relationship between users and effectively enhances the network operational efficiency at the cost of relatively low delay.

Abstract Background Programmed death-ligand 1 (PD-L1) is an immunosuppressor that plays an important role in cancer treatments. Although majority of the studies demonstrated that PD-L1 expression was regulated by cellular intrinsic and extrinsic controls, and IFN-γ was a key molecule of extrinsic control, other studies imply that other cytokines play important roles in PD-L1 expression. In this study, we investigated the regulation of PD-L1 by chemokine signaling pathway in gastric cancer (GC) cells. Methods Bioinformatics was used to explore the PD-L1-related genes in GC and propose a hypothesis. PD-L1 and CXCR3 expression were detected by western blot in SGC7901 and MKN74 cell lines. Meanwhile, PD-L1 and CXCR3 expressions were immunohistochemically assessed for their relevance. Moreover, PD-L1, pSTAT3 and pAkt were detected after treatment with CXCL9/10/11. Furthermore,PD-L1, pSTAT3 and pAkt were evaluated after blocking chemokine signaling in SGC7901 cells. Results Based on online database analysis, CXCL9/10/11-CXCR3 is proposed to upregulate PD-L1 expression by activating the STAT and PI3K-Akt pathways. This hypothesis was confirmed by in vitro and vivo experiments. CXCR3 and PD-L1 were expressed in GC cell lines and tissues, and the expression of CXCR3 and PD-L1 was positively related. PD-L1 was upregulated after treatment with CXCL9/10/11, accompanied by activation of STAT3 and Akt. After blocking chemokine signaling, upregulation of PD-L1 and activation of STAT3 and Akt were diminished. Conclusions CXCL9/10/11-CXCR3 upregulated the expression of PD-L1 by activating the STAT and PI3K-Akt signaling pathways in GC cells. There was a significant positive correlation between the expression of PD-L1 and CXCR3 in gastric cancer patient tissues.

The C-X-C motif chemokine receptor 4 (CXCR4) pathway can promote tumor metastasis but is dependent on cross talk with other signaling pathways. The MET proto-oncogene (c-MET) participates in metastasis and is highly expressed in gastric cancer. However, the relationship between CXCR4 and c-MET signaling and their mechanisms of action in gastric cancer metastasis remain unclear. In this study, in vitro experiments demonstrated that C-X-C motif chemokine ligand 12 (CXCL12)/CXCR4 induces epithelial-mesenchymal transition (EMT) and promotes migration in gastric cancer cells, which is accompanied by c-MET activation. These phenomena were reversed by c-MET inhibition. Further investigation revealed that c-MET activation correlated with its interaction with caveolin 1 in lipid rafts, induced by CXCL12. In clinical samples, we observed a significant positive association between CXCR4 expression and c-MET phosphorylation (r = 0.259, P = .005). Moreover, samples expressing both receptors were found to indicate significantly poorer patient prognosis (P < .001). These results suggest that CXCL12 induces EMT at least partially through cross talk between CXCR4 and c-MET signaling. In addition, changes in these pathways could have clinical importance for the treatment of gastric cancer.

Mobile crowd sensing (MCS) is becoming a popular paradigm to collect information, which has the potential to change people's life. However, MCS is vulnerable to security threats due to the increasing reliance on communication and computing. The challenges of unique security and privacy caused by MCS include privacy protection, integrity, confidentiality, and availability. To tackle these issues concurrently, we present the design of a dynamical credibility assessment of privacy-preserving (CAPP) strategy, a novel credibility assessment-based solution to protect privacy in opportunistic MCS, which is able to cope with malicious attacks and privacy protection even against intelligent MCS entities. In CAPP, the sensing data are dynamically split into slices and the number of slices is based on the trust of encountered nodes. Specially, node trust is assessed in two dimensions including the quality of contribution trust and social trust, which indicates how likely a node can fulfill its functionality and how trustworthy the relationship between a node and other nodes will be, respectively. Moreover, the secret sharing scheme and an anonymous strategy ensure the data integrity and the anonymity of participants. The effectiveness in privacy protection and efficiency of the proposed scheme are validated through theoretical analysis and numerical results.

Abstract To meet the ever-increasing demands of mobile traffic, femtocells are considered as one of the promising solutions. In this paper, we study a sensing-based resource allocation scenario in cognitive femtocell networks and present an efficient distributed imperfect-spectrum-sensing-based resource allocation (DIRA) algorithm while considering the channel uncertainty to maximize the total data rate of cognitive femtocell networks by jointly optimizing both subchannel assignment and power allocation taking into account the influence of the sensing accuracy. However, the general optimization problem turns out to be a mixed integer programming problem. In order to make it tractable, the original optimization problem is divided into two sub-optimization problems,namely,optimal subchannel allocation and optimal power allocation. Specifically, the proposed distributed fairness-based subchannel allocation (DFSA) algorithm guarantees fairness by introducing channel condition difference and satisfaction degree as the indicators of subchannel allocation. Additionally, optimal power allocation with the consideration of imperfect spectrum sensing and interference uncertainty is performed using the proposed chance-constrained power optimization (CPO) algorithm. Bernstein’s approximation is conducted to make the chance constraint tractable. Simulation results illustrate that the distributed imperfect-spectrum-sensing-based resource allocation (DIRA) algorithm can provide considerable fairness among femtocells and at the same time maximize the total data rate of the cognitive femtocell network.

This study proposes a multi-ary modulation chirp spread spectrum algorithm specific for the unmanned aerial vehicles field. It further introduces the corresponding fractional Fourier transform de-spreading algorithm and the hardware implementation of the software radio-based communication system to validate the algorithm's better anti-interference performance in the wide-band non-stationary interference environment.

Background: Trust and conflict represent the critical foundation characterising the inter-firm relationship of cooperation and competition, and their co-existence as coopetition within an alliance partnership. The literature has often regarded conflict and trust as uni-dimensional variables to clarify their interactive influences. However, few studies has explicitly investigate how these two opposite forces and their sub-dimensions may interact and create synergic effects in alliance partnerships in emerging economies. Objectives: This study applies a coopetition perspective to articulate the complex interactive nature of conflict and trust between partners, aiming at revealing how specific patterns of conflict (task and emotional) and trust (cognitive and affective) interact with each other in impacting the focal firm’s performance within the alliance partnership. Method: Using survey data collected from 490 sampled firms in China, we ran three regression models to test four hypotheses from the interactive matrix between different dimensions of conflict and trust. Results: The results indicate that the coupled pattern (the interaction between emotional conflict and affective trust) and the compatible pattern (the interaction between task conflict and cognitive trust) could improve firm performance, whereas the dysfunctional pattern (the interaction between emotional conflict and cognitive trust) and the mismatched pattern (the interaction between task conflict and affective trust) could harm firm performance within alliance partnerships. Conclusion: The new findings imply diverse ways to combine conflict and trust to achieve the best synergistic effect for allied firms in emerging economies, and thus extend and enrich the literature by providing contextual knowledge regarding ‘conflict and trust as coopetition phenomena’ in relevant fields.

The use of dynamic TDD technology in heterogeneous network can effectively increase the system throughput and improve the performance of the system.Due to the limitation of signaling control and other issues,there is usually a dynamic switching between the traditional seven fixed sub-frame ratios in the licensed bands.But as a complement to the LTE system worked in the licensed bands,the unlicensed bands can achieve a more flexible and complete dynamic sub-frame configuration without considering signaling control and other issues.Two new dynamic sub-frame configuration algorithms in unlicensed bands were proposed and compared with traditional static sub-frame configuration,then the impact of dynamic sub-frame allocation algorithms on system performance was verified by LAA system level simulation platform.The results show that the proposed dynamic sub-frame configuration strategies can effectively improve the resource utilization and the overall system throughput.

The high antimicrobial activity of epigallocatechin gallate (EGCG), the most bioactive component of tea polyphenol with a number of health benefits, is well-known. However, little is known about the mechanism involved. Here, we discovered the relationship between reactive oxygen species (ROS), the Cpx system, and EGCG-mediated cell death. We first found an increase in ampicillin resistance as well as the transcription level of a LD-transpeptidase (LD-TPase) involved in cell wall synthesis; ycbB transcription was upregulated whereas that of another LD-TPase, ynhG, appeared to be constant after a short exposure of Escherichia coli to sub-inhibitory doses of EGCG. Additionally, the transcription level of cpxP, a downstream gene belonging to the Cpx regulon, was positively correlated with the concentration of EGCG, and significant upregulation was detected when cells were treated with high doses of EGCG. Through analysis of a cpxR deletion strain (ΔcpxR), we identified a constant ROS level and a notable increase in the survival rate of ΔcpxR, while the ROS level increased and the survival rate decreased remarkably in the wild-type strain. Furthermore, thiourea, which is an antioxidant, reduced the ROS level and antimicrobial activity of EGCG. Taken together, these results suggest that EGCG induces ROS formation by activating the Cpx system and mediates cell death.

Nitric oxide (NO), a well-known signaling molecule plays an important role in abiotic and biotic stress-induced production of plant secondary metabolites. In this study, roles of NO in water stress-induced tanshinone production in Salvia miltiorrhiza hairy roots were investigated. The results showed that accumulations of four tanshinone compounds in S. miltiorrhiza hairy roots were significantly stimulated by sodium nitroprusside (SNP, a NO donor) at 100 μM. Effects of SNP were just partially arrested by the mevalonate (MVA) pathway inhibitor (mevinolin), but were completely inhibited by the 2-C-methyl-d-erythritol-4-phosphate pathway (MEP) inhibitor (fosmidomycin). The increase of tanshinone accumulation and the up-regulation of HMGR and DXR expression by PEG and ABA treatments were partially inhibited by an inhibitor of NO biosynthesis (Nω-nitro-L-arginine methyl ester (L-NAME)) and a NO scavenger (2-(4-Carboxyphenyl)- 4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (c-PTIO)). Simultaneously, NO generation in the hairy roots was triggered by PEG and ABA, and the effects were also arrested by c-PTIO and L-NAME. These results indicated that NO signaling probably plays a central role in water stress-induced tanshinone production in S. miltiorrhiza hairy roots. SNP mainly stimulated the MEP pathway to increase tanshinone accumulation.

The economic production of cellulosic biofuel requires efficient and full utilization of all abundant carbohydrates naturally released from plant biomass by enzyme cocktails. Recently, we reconstituted the Neurospora crassa xylodextrin transport and consumption system in Saccharomyces cerevisiae, enabling growth of yeast on xylodextrins aerobically. However, the consumption rate of xylodextrin requires improvement for industrial applications, including consumption in anaerobic conditions. As a first step in this improvement, we report analysis of orthologues of the N. crassa transporters CDT-1 and CDT-2. Transporter ST16 from Trichoderma virens enables faster aerobic growth of S. cerevisiae on xylodextrins compared to CDT-2. ST16 is a xylodextrin-specific transporter, and the xylobiose transport activity of ST16 is not inhibited by cellobiose. Other transporters identified in the screen also enable growth on xylodextrins including xylotriose. Taken together, these results indicate that multiple transporters might prove useful to improve xylodextrin utilization in S. cerevisiae. Efforts to use directed evolution to improve ST16 from a chromosomally-integrated copy were not successful, due to background growth of yeast on other carbon sources present in the selection medium. Future experiments will require increasing the baseline growth rate of the yeast population on xylodextrins, to ensure that the selective pressure exerted on xylodextrin transport can lead to isolation of improved xylodextrin transporters.

Ecological interactions between aboveground and belowground biodiversity have received many attentions in the recent decades. Although soil biodiversity declined with the decrease of plant diversity, many previous studies found plant species identities were more important than plant diversity in controlling soil biodiversity. This study focused on the responses of soil biodiversity to the altering of plant functional groups, namely overstory and understory vegetations, rather than plant diversity gradient. We conducted an experiment by removing overstory and/or understory vegetation to compare their effects on soil microbial phospholipid fatty acid (PLFA) and nematode diversities in eucalyptus monocultures. Our results indicated that both overstory and understory vegetations could affect soil microbial PLFA and nematode diversities, which manifested as the decrease in Shannon-Wiener diversity index (H') and Pielou evenness index (J) and the increase in Simpson dominance index (λ) after vegetation removal. Soil microclimate change explained part of variance of soil biodiversity indices. Both overstory and understory vegetations positively correlated with soil microbial PLFA and nematode diversities. In addition, the alteration of soil biodiversity might be due to a mixing effect of bottom-up control and soil microclimate change after vegetation removal in the studied plantations. Given the studied ecosystem is common in humid subtropical and tropical region of the world, our findings might have great potential to extrapolate to large scales and could be conducive to ecosystem management and service.