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This is an article in the field of process mineralogy. The occurrence of zinc, associated dispersed elements Ga and Ge and the distribution characteristics of the main carrier minerals of a zinc ore in China are studied in detail by means of chemical analysis, microscope analysis and MLA mineral automatic quantitative technology.The results indicate that the zinc ore contains Zn 4.87%, Ga 4.10 g/t and Ge 59.00 g/t, no independent minerals of dispersed elements Ga and Geare found, Ga and Ge mainly occur in sphalerite. The theoretical recovery of Zn, Ga and Ge from sphalerite (including hemimorphite) are about 95%, 56% and 93% respectively. A small part of colloidal and fine grained sphalerite is difficult to obtain dissociation and easy to be lost in tailings, which has a certain effect on the recovery of zinc.

Abstract Osteosarcoma (OS) is an aggressive bone tumor with strong invasiveness, rapid metastasis, and dreadful mortality. Chemotherapy is a commonly used approach for OS treatment but is limited by the development of drug resistance and long-term adverse effects. To date, OS still lacks the curative treatment. Herein, we fabricated pyrite-based nanoparticles (FeS2@CP NPs) as synergetic therapeutic platform by integrating photothermal therapy (PTT) and chemo-dynamic therapy (CDT) into one system. The synthetic FeS2@CP NPs showed superior Fenton reaction catalytic activity. FeS2@CP NPs-based CDT efficaciously eradicated the tumor cells by initiating dual-effect of killing of apoptosis and ferroptosis. Furthermore, the generated heat from FeS2@CP under near-infrared region II (NIR-II) laser irradiation could not only inhibit tumor’s growth, but also promote tumor cell apoptosis and ferroptosis by accelerating •OH production and GSH depletion. Finally, the photothermal/NIR II-enhanced CDT synergistic therapy showed excellent osteosarcoma treatment effects both in vitro and in vivo with negligible side effects. Overall, this work provided a high-performance and multifunctional Fenton catalyst for osteosarcoma synergistic therapy, which provided a pathway for the clinical application of PTT augmented CDT.

Reliable and continuous information on cropping intensity is crucial for assessing cropland utilization and formulating policies regarding cropland protection and management. However, there is still a lack of high-resolution cropping intensity maps for recent years, particularly in fragmented agricultural regions. In this study, we combined Landsat-8 and Sentinel-2 imagery to generate cropping intensity maps from 2019 to 2023 at a 10 m resolution for Shaanxi Province, China. First, the satellite imagery was harmonized to construct 10-day composite enhanced vegetation index (EVI) time series. Then, the cropping intensity was determined by counting the number of valid EVI peaks within a year. Assessment based on 578 sample points showed a high level of accuracy, with overall accuracy and Kappa coefficient values exceeding 0.96 and 0.93, respectively. We further analyzed the spatiotemporal patterns of cropping intensity and generated a map of abandoned cropland in Shaanxi. The results indicated that cropland in Shaanxi Province was mainly utilized for single-cropping (52.9% of area), followed by double-cropping (35.2%), with non-cropping accounting for 11.9%. Cropping intensity tended to be lower in the north and higher in the south. Temporally, the average cropping intensity of Shaanxi increased from 1.1 to over 1.3 from 2019 to 2023. Despite this upward trend, large areas of cropland were abandoned in northern Shaanxi. These results demonstrate the potential of utilizing Landsat-8 and Sentinel-2 imagery to identify cropping intensity dynamics in fragmented agricultural regions and to guide more efficient cropland management.

Abstract The third most often diagnosed disease globally and the second most prevalent cause of cancer-related death is colorectal cancer (CRC). Numerous human malignancies have been identified to have high expression of ADORA2A. However, it is still ambiguous about its function in CRC. RNA-seq with stable transfected SETDB1 knockdown cells was used to identify differentially expressed genes. Further, knockdown of ADORA2A in CRC cell lines SW620 and HCT116 was performed with siRNA and over expression of ADORA2A in SW480 cells was conducted with plasmids. CCK8, colony formation, wound healing, and transwell assay were used to detect the effects of cell proliferation, migration, and invasion after knockdown and over expression of ADORA2A. Also, apoptosis was analyzed by flow cytometry, apoptosis-related proteins and key PI3K/AKT pathway proteins were detected using Western blotting. ADORA2A was identified after RNA-seq analysis and played an important role in CRC prognosis. ADORA2A was relatively high in SW620 and HCT116 cell lines compared to SW480 cell lines. ADORA2A knockdown in SW620 and HCT116 inhibited cell proliferation, migration, and invasion, while ADORA2A overexpression had the opposite effect. In addition, ADORA2A also impacted the expression of apoptosis-related proteins, including Bcl-2, Bax, Cleaved caspase-3 and Cleaved caspase-9, and reduced apoptosis. Furthermore, this process may include the PI3K/AKT signaling pathway. ADORA2A promotes CRC progression and inhibits apoptosis by the PI3K/AKT signaling pathway. It may contribute to the management and treatment of CRC.

This is a paper in the field of process mineralogy. A silica-type tungsten and molybdenum mine in Shaanxi has diverse ore types and large variations in tungsten and molybdenum grades, and it is difficult to improve the concentrate grade and recovery. Multiple technics including microscopic observation, X-ray diffraction (XRD), scanning electron microscope energy dispersive spectrometer(SEM-EDS) and mineral liberation analyser (MLA) were adopted to study the mineral compositions, dissemination characteristics of target minerals and the distributions of valuable elements of the ore, and the beneficiation process scheme was explored and optimized. The results show that the valuable elements are tungsten and molybdenum, and the main target minerals are scheelite and molybdenite. The content of clay minerals such as soapstone and montmorillonite is high, which are the main harmful minerals affecting the flotation recovery of tungsten and molybdenum. Scheelite is mainly coarse- to medium-grained, and molybdenite is medium- to fine-grained. The proportion of -0.02 mm refractory particle size of molybdenite is up to 31%, which requires fine grinding to be liberated. The theoretical grade of molybdenum and tungsten concentrate by flotation of molybdenite and scheelite is expected to be 58% and 67%, and the theoretical recovery is about 76% and 92%, respectively. By adjusting the reagent system, the dispersion and inhibition of clay minerals such as saponite and montmorillonite, which are easy to float and slime, was strengthened in the beneficiation process, reducing the influence on the recovery of tungsten and molybdenum.

Background: Generalized convulsive status epilepticus (GCSE) is one of the most challenging life-threatening neurological emergencies. If GCSE becomes super-refractory, it is associated with significant mortality. Although aggressive management of prolonged status epilepticus was conducted, the mortality has not decreased since the late 1990s. Objectives: The present study aimed to explore the risk factors for progression to super-refractory in patients with generalized convulsive status epilepticus (GCSE). Moreover, we illustrated the risk factors for mortality in GCSE patients. Design: An observational retrospective cohort study. Methods: We conducted a retrospective study of patients with GCSE admitted to our neurocritical unit, in Guangzhou, China, from October 2010 to February 2021. The data of sociodemographic information, etiology, laboratory results, treatment, and prognosis were collected and analyzed. Results: A total of 106 patients were enrolled; 51 (48%) of them developed super-refractory status epilepticus (SRSE). Multivariate logistic regression analysis demonstrated that patients with autoimmune encephalitis ( p = 0.015) and intracranial infection ( p = 0.019) are likely to progress to SRSE. The in-hospital mortality was 11.8% and 9.1% for patients in the SRSE and non-SRSE groups, respectively ( p = 0.652). Multivariate logistic regression analysis showed that neutrophil-to-lymphocyte ratios (NLR) at admission were independently associated with in-hospital mortality. Up to 31.4% of SRSE patients and 29.1% of non-SRSE patients died within 6 months after discharge ( p = 0.798). Multivariate logistic regression analysis showed that plasma exchange (PE) was a protective factor for 6-month mortality. A high NLR at discharge was a risk factor for 6-month mortality. Conclusion: In the current study, about 48% of GCSE patients progressed to SRSE. Regarding etiology, autoimmune encephalitis or intracranial infection was prone to SRSE. No significant differences were observed in the in-hospital and 6-month mortality between SRSE and non-SRSE groups. Multivariate logistic regression analysis showed that NLR at admission and discharge was an independent predictor of in-hospital and 6-month mortality, respectively. Moreover, PE significantly reduced the 6-month mortality.

High-temperature and drought events significantly impact crop growth and development. In the soybean-producing region of the Guanzhong Plain in China, understanding the dynamics of these climatic phenomena is vital for soybean yield preservation. Through a fixed-position observation experiment that analyzed four growth stages, nine agronomic traits, and soybean yield per unit area from 1998 to 2023, this research evaluated the characteristics of high-temperature and drought processes in various growth stages. It also examined the influence of high-temperature processes, drought processes, and their combined effects on agronomic traits and yield. The results indicate the following: (1) High temperature was a constant factor during the soybean growth period, with temperature-related indices markedly surpassing those related to drought. Notably, the occurrence of high-temperature and drought events was more prevalent during the flowering–podding stage than at the podding or grain-filling stages. (2) High temperature profoundly affected soybean yield components, primarily through a decrease in the number of grains per plant during the flowering–podding stage, subsequently impacting the grain weight per plant and yield. In years with extremely high temperatures, the soybean plant height was reduced by 6.1 to 15 cm, the main stem node number decreased by 0.1 to 2.9, the branch number decreased by 0.2 to 0.6, the number of pods per plant decreased by 4.8 to 13.7, the number of grains per pod decreased by 0.1 to 0.3, the number of grains per plant decreased by 13.5 to 32.6, the grain weight per plant decreased by 3.8 to 6.9 g, and the 100-grain weight decreased by 0.1 to 4.5 g. The common impact of high temperature combined with drought processes in different growth stages was reflected in the reduction in the number of branches by 0.1 to 1.4 and the reduction in the number of grains per pod by 0.02 to 13.7. This study underscores the importance of addressing the quantitative effects of climate change and extreme weather on soybean yield, which could help to develop effective adaptation and mitigation strategies.

Abstract Cancer is a leading public health problem worldwide. Its treatment remains a daunting challenge, although significant progress has been made in existing treatments in recent years. A large concern is the poor therapeutic effect due to lack of specificity and low bioavailability. Gene therapy has recently emerged as a powerful tool for cancer therapy. However, delivery methods limit its therapeutic effects. Exosomes, a subset of extracellular vesicles secreted by most cells, have the characteristics of good biocompatibility, low toxicity and immunogenicity, and great designability. In the past decades, as therapeutic carriers and diagnostic markers, they have caught extensive attention. This review introduced the characteristics of exosomes, and focused on their applications as delivery carriers in DNA, messenger RNA (mRNA), microRNA (miRNA), small interfering RNA (siRNA), circular RNA (circRNA) and other nucleic acids. Meanwhile, their application in cancer therapy and exosome-based clinical trials were presented and discussed. Through systematic summarization and analysis, the recent advances and current challenges of exosome-mediated nucleic acid delivery for cancer therapy are introduced, which will provide a theoretical basis for the development of nucleic acid drugs. Graphical Abstract

Abstract Mesenchymal stem cell (MSC)-based therapy has been considered as a promising approach targeting a variety of intractable diseases due to remarkable multiple effect of MSCs, such as multilineage differentiation, immunomodulatory property, and pro-regenerative capacity. However, poor engraftment, low survival rate of transplanted MSC, and impaired donor-MSC potency under host age/disease result in unsatisfactory therapeutic outcomes. Enhancement strategies, including genetic manipulation, pre-activation, and modification of culture method, have been investigated to generate highly functional MSC, and approaches for MSC pre-activation are highlighted. In this review, we summarized the current approaches of MSC pre-activation and further classified, analysed the scientific principles and main characteristics of these manipulations, and described the pros and cons of individual pre-activation strategies. We also discuss the specialized tactics to solve the challenges in this promising field so that it improves MSC therapeutic functions to serve patients better.

The waste lithium ion battery contains a large number of cobalt, copper, aluminum, lithium, manganese, nickel and other metals, and also contains a large number of graphite and other carbonaceous powder. It is difficult to characterize this type of samples by traditional analytical methods. MLA system is mainly used to study the phase composition and valuable metal phases dissemination of a graphite lithium battery waste sample. The results show that the valuable metal phases are mainly lithium nickel-cobalt manganate (NCM) and alumina, and a small amount of lithium nickel-cobalt aluminate (NCA), lithium lithium cobalt oxides (LCO), lithium manganate (LMO) and lithium iron phosphate (LFP). The research results of valuable metal phases dissemination provide a theoretical basis for the comprehensive utilization of the valuable metal resources in this type of electrode material.

IntroductionIt has long been recognized that inflammation to dermatophyte infection is different among various hosts, but the mechanism underlying is still not well understood. Toll-like receptor (TLR2), mediates the innate immune response against dermatophyte infection and is very important to trigger the inflammatory response to dermatophytes. Considering the different amino acid sequences and structures of TLR2, we speculated that TLR2 from different hosts will activate the downstream signal pathways to varying degrees, resulting in different inflammatory responses to dermatophytes.MethodsIn this study, we constructed the mice-human fusion TLR2 expressed HaCaT (mhTLR2-HaCaT) by replacing the extracellular ligand recognition region of human TLR2 with that of the mouse. Then hTLR2-HaCaT cells and mhTLR2-HaCaT cells were infected with T. rubrum and M. canis for 24 h followed by immunoblotting to asses associated proteins of p38 and JNK signal pathway.ResultsCompared with that of human TLR2 expressed HaCaT (hTLR2-HaCaT), levels of phosphorylated p38 protein were increased in mhTLR2-HaCaT cells stimulated by T. rubrum for 24 h, and levels of phosphorylatedJNK and c-Jun protein were increased in mhTLR2-HaCaT cells whenstimulated with M. canis for 24 h.DiscussionCompared with hTLR2-HaCaT cells, p38 and JNK signal pathwayswere activated in mhTLR2-HaCaT after being infected by Trichophyton rubrumand Microsporum canis, respectively. Since p38 and JNK are the mainpathways that transduce the signal for host recognition of dermatophytes andmediate the downstream inflammatory response, it suggested that theinterspecific difference of TLR2 ectodomain may be one of the reasons for thedifferent inflammatory manifestations between humans and mice infected bythese two dermatophytes. Quite especially, the mouse-derived TLR2extracellular recognition region is more effective in recognizing T. rubrum andM. canis to activate the downstream signal pathways, resulting in a tenserinflammatory response against these two dermatophytes.

Abstract Background Fungal cell wall polysaccharides maintain the integrity of fungi and interact with host immune cells. The immunomodulation of fungal polysaccharides has been demonstrated in previous studies. However, the effect of chitin-rich heteroglycan extracted from Sporothrix schenckii sensu stricto on the immune response has not been investigated. Results In this study, chitin-rich heteroglycan was extracted from S. schenckii sensu stricto, and immunomodulation was investigated via histopathological analysis of skin lesions in a mouse model of sporotrichosis and evaluation of the phagocytic function and cytokine secretion of macrophages in vitro. The results showed that the skin lesions regressed and granulomatous inflammation was reduced in infected mice within 5 weeks. Moreover, heteroglycan promoted the fungal phagocytosis by macrophages and modulated the cytokine secretion. Heteroglycan upregulated TNF-α expression early at 24 h and IL-12 expression late at 72 h after incubation, which might result from moderate activation of macrophages and contribute to the subsequent adaptive immune response. Conclusions Chitin-rich heteroglycan extracted from S. schenckii sensu stricto potentiated fungal clearance in a mouse model of sporotrichosis. Moreover, chitin-rich heteroglycan promoted fungus phagocytosis by macrophages and modulated cytokines secretion. These results might indicate that chitin-rich heteroglycan could be considered as an immunomodulator used in the treatment of sporotrichosis.

Colorectal cancer (CRC) is the third most common cancer worldwide and the second leading cause of cancer-related deaths in the world. It is urgent to search for safe and effective therapies to address the CRC crisis. The siRNA-based RNA interference targeted silencing of PD-L1 has extensive potential in CRC treatment but is limited by the lack of efficient delivery vectors. In this work, the novel cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODNs)/siPD-L1 co-delivery vectors AuNRs@MS/CpG ODN@PEG-bPEI (ASCP) were successfully prepared by two-step surface modification of CpG ODNs-loading and polyethylene glycol-branched polyethyleneimine-coating around mesoporous silica-coated gold nanorods. ASCP promoted dendritic cells (DCs) maturation by delivering CpG ODNs, exhibiting excellent biosafety. Next, mild photothermal therapy (MPTT) mediated by ASCP killed tumor cells and released tumor-associated antigens, further promoting DC maturation. Furthermore, ASCP exhibited mild photothermal heating-enhanced performance as gene vectors, resulting in an increased PD-L1 gene silencing effect. Enhanced DCs maturity and enhanced PD-L1 gene silencing significantly promoted the anti-tumor immune response. Finally, the combination of MPTT and mild photothermal heating-enhanced gene/immunotherapy effectively killed MC38 cells, leading to strong inhibition of CRC. Overall, this work provided new insights into the design of mild photothermal/gene/immune synergies for tumor therapy and may contribute to translational nanomedicine for CRC treatment.

Objective: To explore the activation of TLR2/c-Jun and NF-κB signaling pathway in human keratinocytes infected by different ecological classifications of dermatophytes. Methods: Total and phosphorylated p65, relb, IκB, and c-Jun in HaCaT cells were detected by immunoblotting following co-culture with either Trichophyton rubrum(T. rubrum) or Microsporum gypseum(M. gypseum) for 24 h. Immunoblotting was used to assess expression levels of TLR2, c-Jun, and phosphorylated c-Jun after co-culture of TLR2 deficient HaCaT cells (HaCaT TLR2-/- cells) with T. rubrum and M. gypseum for 24 h. Results: Co-culture of HaCaT cells with M. gypseum, but not T. rubrum, significantly increased the levels of phosphorylated c-Jun. However, neither T. rubrum nor M. gypseum induced significant changes in the total and phosphorylated p56, relb, and IκB in HaCaT cells. Following TLR2 knockout in HaCaT cells, the level of phosphorylated c-Jun decreased significantly in HaCaT TLR2-/- cells co-cultured with T. rubrum, but not M. gypseum. Conclusions: T. rubrum and M. gypseum can activate c-Jun signaling pathway through TLR2 in keratinocytes, without activation of NF-κB signaling pathway. TLR2, together with other receptors, may dominate the differential induction of c-Jun pathway in keratinocytes infected by T. rubrum and M. gypseum.

Abstract Background Synovial fibroblasts (SFs) with the abnormal expressions of miRNAs are the key regulator in rheumatoid arthritis (RA). Low-expressed miR-140-3p was found in RA tissues. Therefore, we attempted to investigate the effect of miR-140-3p on SFs of RA. Methods RA and normal synovial fibrous tissue were gathered. The targets of miR-140-3p were found by bioinformatics and luciferase analysis. Correlation between the expressions of miR-140-3p with sirtuin 3 (SIRT3) was analyzed by Pearson correlation analysis. After transfection, cell viability and apoptosis were detected by cell counting kit-8 and flow cytometry. The expressions of miR-140-3p, SIRT3, Ki67, Bcl-2, Bax, and cleaved Caspase-3 were detected by RT-qPCR or western blot. Results Low expression of miR-140-3p and high expression of SIRT3 were found in RA synovial fibrous tissues. SIRT3 was a target of miR-140-3p. SIRT3 expression was negatively correlated to the expression of miR-140-3p. MiR-140-3p mimic inhibited the MH7A cell viability and the expressions of SIRT3, Ki67, and Bcl-2 and promoted the cell apoptosis and the expressions of Bax and cleaved Caspase-3; miR-140-3p inhibitor showed an opposite effect to miR-140-3p mimic on MH7A cells. SIRT3 overexpression not only promoted the cell viability and inhibited cell apoptosis of MH7A cells but also reversed the effect of miR-140-3p mimic had on MH7A cells. Conclusions The results in this study revealed that miR-140-3p could inhibit cell viability and promote apoptosis of SFs in RA through targeting SIRT3.

The outbreak of the coronavirus disease 2019 (COVID-19) has resulted in enormous losses worldwide. Through effective control measures and vaccination, prevention and curbing have proven significantly effective; however, the disease has still not been eliminated. Therefore, it is necessary to develop a simple, convenient, and rapid detection strategy for controlling disease recurrence and transmission. Taking advantage of their low-cost and simple operation, point-of-care test (POCT) kits for COVID-19 based on the lateral flow assay (LFA) chemistry have become one of the most convenient and widely used screening tools for pathogens in hospitals and at home. In this review, we introduce essential features of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, compare existing detection methods, and focus on the principles, merits and limitations of the LFAs based on viral nucleic acids, antigens, and corresponding antibodies. A systematic comparison was realized through summarization and analyses, providing a comprehensive demonstration of the LFA technology and insights into preventing and curbing the COVID-19 pandemic.

PurposeTo construct an optimal radiomics model for preoperative prediction micropapillary pattern (MPP) in adenocarcinoma (ADC) of size ≤ 2 cm, nodule type was used for stratification to construct two radiomics models based on high-resolution computed tomography (HRCT) images.Materials and MethodsWe retrospectively analyzed patients with pathologically confirmed ADC of size ≤ 2 cm who presented to three hospitals. Patients presenting to the hospital with the greater number of patients were included in the training set (n = 2386) and those presenting to the other two hospitals were included in the external validation set (n = 119). HRCT images were used for delineation of region of interest of tumor and extraction of radiomics features; dimensionality reduction was performed for the features. Nodule type was used to stratify the data and the random forest method was used to construct two models for preoperative prediction MPP in ADC of size ≤ 2 cm. Model 1 included all nodule types and model 2 included only solid nodules. The receiver operating characteristic curve was used to assess the prediction performance of the two models and independent validation was used to assess its generalizability.ResultsBoth models predicted ADC with MPP preoperatively. The area under the curve (AUC) of prediction performance of models 1 and 2 were 0.91 and 0.78, respectively. The prediction performance of model 2 was lower than that of model 1. The AUCs in the external validation set were 0.81 and 0.72, respectively. The DeLong test showed statistically significant differences between the training and validation sets in model 1 (p = 0.0296) with weak generalizability. There was no statistically significant difference between the training and validation sets in model 2 (p = 0.2865) with some generalizability.ConclusionNodule type is an important factor that affects the performance of radiomics predictor model for MPP with ADC of size ≤ 2 cm. The radiomics prediction model constructed based on solid nodules alone, can be used to evaluate MPP and may contribute to proper surgical planning in patients with ADC of size ≤ 2 cm.

PurposeThis study established and verified a radiomics model for the preoperative prediction of the Ki67 index of gastrointestinal stromal tumors (GISTs).Materials and MethodsA total of 344 patients with GISTs from three hospitals were divided into a training set and an external validation set. The tumor region of interest was delineated based on enhanced computed-tomography (CT) images to extract radiomic features. The Boruta algorithm was used for dimensionality reduction of the features, and the random forest algorithm was used to construct the model for radiomics prediction of the Ki67 index. The receiver operating characteristic (ROC) curve was used to evaluate the model’s performance and generalization ability.ResultsAfter dimensionality reduction, a feature subset having 21 radiomics features was generated. The generated radiomics model had an the area under curve (AUC) value of 0.835 (95% confidence interval(CI): 0.761–0.908) in the training set and 0.784 (95% CI: 0.691–0.874) in the external validation cohort.ConclusionThe radiomics model of this study had the potential to predict the Ki67 index of GISTs preoperatively.

Persistent hyper-inflammation is a distinguishing pathophysiological characteristic of chronic wounds, and macrophage malfunction is considered as a major contributor thereof. In this review, we describe the origin and heterogeneity of macrophages during wound healing, and compare macrophage function in healing and non-healing wounds. We consider extrinsic and intrinsic factors driving wound macrophage dysregulation, and review systemic and topical therapeutic approaches for the restoration of macrophage response. Multidimensional analysis is highlighted through the integration of various high-throughput technologies, used to assess the diversity and activation states as well as cellular communication of macrophages in healing and non-healing wound. This research fills the gaps in current literature and provides the promising therapeutic interventions for chronic wounds.

Acute leukemia is a common hematological malignancy. Despite recent promising progress, the prognosis of acute leukemia patients remains to be improved. New therapies are therefore still needed. Salmonella typhimurium has been shown to be highly effective as an anti-tumor agent in many solid cancer models, but it has not been applied in acute leukemia. Here, we report an attenuated Salmonella typhimurium strain, VNP20009, can induce apoptosis in multiple types of leukemia cells both in vivo and in vitro. Furthermore, VNP20009 significantly inhibited the proliferation of MLL-AF9-induced acute myeloid leukemia cells and prolonged the survival of the AML-carrying mice. VNP20009 restored the counts of white blood cell (WBC) and its five subsets in peripheral blood (PB) to near-physiological values, and elevated the levels of certain cytokines, such as tumor necrosis factor-α (TNF-α), leukemia inhibitory factor (LIF), interferon-γ (IFN-γ), chemokine C-X-C motif ligand-10 (CXCL-10) and C-C motif ligand-2 (CCL-2). Moreover, the ratio of immune cells, including natural killer cells (NKs), CD4+ Th1-type cells and CD8+ IFN-γ-producing effector T cells were highly upregulated in the AML mice treated with VNP20009. The results of the present study potentially provide an alternative therapeutic strategy for hematologic malignancies through boosting the innate and adaptive anti-tumor immunity.

Skin regeneration is a vexing problem in the field of regenerative medicine. A bioactive molecule-based strategy has been frequently used in skin wound healing in recent years. Bioactive molecules are practical tools for regulating cellular processes and have been applied to control cellular differentiation, dedifferentiation, and reprogramming. In this review, we focus on recent progress in the use of bioactive molecules in skin regenerative medicine, by which desired cell types can be generated in vitro for cell therapy and conventional therapeutics can be developed to repair and regenerate skin in vivo through activation of the endogenous repairing potential. We further prospect that the bioactive molecule-base method might be one of the promising strategies to achieve in situ skin regeneration in the future.

Assessing the impacts of future climate change on crop yields requires basic research into both the major meteorological factors that affect crop yield and the influence that changes to global circulation patterns have on local meterological parameters. For example, the atmospheric circulation and crop “meteorological yield” and the response of meteorological yield to climate change are positively correlated. Using apple (Malus domestica) production as an example, the present work investigated the link between fruit yield and global circulation factors by using yield data from 28 apple-producing counties in Shaanxi province, China, from 1980 to 2015. We used four methods to isolate apple production and applied a Grey relational analysis of 88 meteorological factors and the associated sequential correlation. We extracted the major climate factors based on the high consistency of climatic factors and the variation trend of meteorological yield of apple, and analyzed the main meteorological factors for the meteorological apple yield of three major apple producing areas by analyzing high-impact atmospheric circulation indices. The climate factors included solar radiation, pan evaporation, accumulated temperature, precipitation, wind speed, maximum temperature, minimum temperature, mean temperature, heat injury over several days, number of frost days during flowering, number of freezing days during dormancy, and annual temperature range. The main meteorological factors affecting annual apple meteorological yield were total solar radiation from April to October, evaporation from April to September, precipitation in April and June to August, and minimum temperature in mid-April. The Southern Oscillation Index (SOI) was the circulation index most closely related to total summer solar radiation, pan evaporation, and precipitation. Correlation analysis showed that the polar vortex area index and sea surface temperature index were important circulation indices affecting climate yield in apple regions. The meteorological yields of apples in zones Ⅰ and Ⅲ were significantly correlated with the ENSO period index, mainly in the autumn and winter. Similar to the conclusions of previous studies, the uncertainty of meteorological yield in the Shaanxi fruit region is predicted to increase under future climate change. Keywords: Apple yield, Shaanxi province, Grey relational analysis, Climate factors, Circulation index

Sweat glands (SGs) are spread over almost the entire surface of the human body and are essential for thermoregulation. Theoretically, tissue-specific stem cells (TSSCs) are excellent candidate cells for the regeneration of SGs due to their genetic stability and differentiation ability. Herein, we attempted to isolate TSSCs derived from adult human sweat glands (ahSGs). ahSGs were localized and identified by H&E staining, double immunofluorescence staining, transmission electron microscope (TEM), and immuno-TEM. We found a population of cells with stem cell characteristics (SGSCs), located in basal myoepithelial cells of the secretory portion of the solenoid bulb. The SGSCs expressed alpha-smooth muscle actin (α-SMA) and showed the typical characteristics of mesenchymal stem cells (MSCs), with a positive antigen profile for CD44, CD73, CD90, and CD105, and had the multilineage differentiation potential to osteoblasts and adipocytes. In addition, the isolated α-SMA positive cells remained stably phenotypic and proliferative cycles at passage 12. This is the first report of successful isolation of MSC-like cells from ahSGs, which may contribute to wound repair and SG regeneration.

Mesenchymal stem cells (MSCs) can affect the microenvironment of a wound and thereby accelerate wound healing. Wnt proteins act as key mediators of skin development and participate in the formation of skin appendages such as hair. The mechanisms of action of MSCs and Wnt proteins on skin wounds are largely unknown. Here, we prepared a Wnt7a-containing conditioned medium (Wnt-CM) from the supernatant of cultured human umbilical cord-MSCs (UC-MSCs) overexpressing Wnt7a in order to examine the effects of this CM on cutaneous healing. Our results revealed that Wnt-CM can accelerate wound closure and induce regeneration of hair follicles. Meanwhile, Wnt-CM enhanced expression of extracellular matrix (ECM) components and cell migration of fibroblasts but inhibited the migratory ability and expression of K6 and K16 in keratinocytes by enhancing expression of c-Myc. However, we found that the CM of fibroblasts treated with Wnt-CM (HFWnt-CM-CM) can also promote wound repair and keratinocyte migration; but there was no increase in the number of hair follicles of regeneration. These data indicate that Wnt7a and UC-MSCs have synergistic effects: they can accelerate wound repair and induce hair regeneration via cellular communication in the wound microenvironment. Thus, this study opens up new avenues of research on the mechanisms underlying wound repair.

Volumetric muscle loss (VML) injury resulted from massive muscle defects and diseases for which there are still no effective therapeutic treatments. This study aimed to investigate the effects of rat adipose-derived mesenchymal stem cells (rASCs) and rASCs-conditioned medium- (CM-) based type I collagen hydrogel on macrophage (MP) transition, myogenesis, and vascularization in the rat VML model. Laser Doppler results demonstrated much higher blood flow in the rASC- and CM-based hydrogel groups. qRT-PCR, hematoxylin and eosin, immunofluorescence, and Sirius Red staining manifested that both rASCs and CM-based hydrogel implantation accelerated muscle repair with upregulated angiogenesis and myogenesis, attenuated inflammation while facilitating M2 transition, and decreased the collagen deposition compared with the hydrogel group. In vitro experiments indicated that factors secreted from polarized M2 MPs could accelerate the migration and tube formation capacities of HUVECs. These results suggested that rASCs exerted immunomodulatory effects on MPs which further enhanced the proangiogenic potential on ECs to promote myogenesis and angiogenesis during muscle repair. These fundamental results support further clinical applications of ASCs for muscle loss injury.

We previously reported that expression of Flotillin 2 (Flot-2), a protein isolated from caveolae/lipid raft domains, increased significantly in nasopharyngeal carcinoma (NPC) compared with normal tissues. Signal transduction through epidermal growth factor receptors (EGFR) and Flot-2 play an important role in cancer development, but their precise role in lung cancer has not been investigated. In this study, we have investigated the correlation between the expression of Flot-2 and EGFR, which increase significantly in non-small cell lung cancer (NSCLC) patients (n=352) compared with non-cancer tissues. Additionally, patients with advanced stages of NSCLC had higher positive expression of Flot-2 and EGFR than patients with early stages. NSCLC patients with increased expression of Flot-2 and EGFR had significantly less overall survival rates than patients with less expression of Flot-2 and EGFR. Taken together, our data suggest that increased expression of Flot-2 and EGFR in NSCLC patients is inversely proportional to the disease prognosis and that increased expression of Flot-2 associated with increased EGFR may serve as a biomarker to predict poor disease prognosis.

We occasionally found that cestode Taenia taeniaeformis in rats favored Sporothrix schenckii infection and survival, causing protracted cutaneous lesions. In this study, we compared the pathology and cytokines profile of rats co-infected with the two pathogens and infected with S. schenckii alone to explore underlying mechanisms. In the co-infection group, there was high expression of β-glucan receptor Dectin-1 in the cutaneous lesions and no multinucleated giant cells, but in the S. schenckii infection group the opposite was observed. Cytokines profiles demonstrated an expected finding that IL-4, commonly expressed in helminth and fungus infection, is undetectable in the two infection groups. In the single fungal infection group, cytokines IFN-γ, IL-10 and IL-17 kept increasing in the first few weeks of infection to a peak which was followed by gradual decrease. This study showed that Dectin-1 and IL-17, which were believed to be the major anti-fungus mechanisms, are Th2 independent and dispensable for clearance of S. schenckii infection, suggesting that S. schenckii has a different molecular recognition pattern and evokes anti-infection mechanisms other than Dectin-1 and IL-17.

Cutaneous Rosai-Dorfman disease is a rare, lymphoproliferative disease. It is benign and self-limited, only involves skin and subcutaneous tissue and typically occurs as histiocyte-rich inflammatory infiltrates, manifesting as erythematous to brown papules, plaques, or nodules, without predilection for site. The authors describe a case of cutaneous Rosai-Dorfman disease in a 72-year-old man who presented erythematous and scaled plaque on the right neck for three months without systemic symptoms. Owing to local involvement, the patient received a surgery to exsect the lesion completely and remained asymptomatic with no signs of recurrence at the 9-month follow up.

ABSTRACT Chromoblastomycosis is a chronic fungal infection. Itraconazole and terbinafine are the most recommended antifungal drugs for chromoblastomycosis, while amphotericin B is not usually recommended. A patient with chromoblastomycosis in our hospital showed poor clinical responses to itraconazole and terbinafine. The fungus isolated from the lesions of this patient was identified as Fonsecaea nubica and numbered zssy0803. In vitro antifungal susceptibilities of F. nubica zssy0803 to terbinafine, amphotericin B, itraconazole, voriconazole and caspofungin were evaluated, as well as the combinations of terbinafine with the other four antifungals. The combined effect of terbinafine and amphotericin B on other 20 clinical F. nubica strains was also evaluated. The minimal inhibitory concentrations of terbinafine, amphotericin B, itraconazole, voriconazole and caspofungin on F. nubica zssy0803 were 0.25 μg/mL, 2 μg/mL, 1 μg/mL, 4 μg/mL and 8 μg/mL, respectively. The combination of terbinafine and amphotericin B showed the lowest fractional inhibitory concentration index of 0.28 to F. nubica zssy0803 in comparison with combinations of terbinafine and the other four antifungal drugs. The combination of terbinafine and amphotericin B was also synergistic for all the other 20 F. nubica strains. Then, the combination of oral terbinafine (500 mg/day) and intralesional injections of amphotericin B (1 mg/mL) was used to treat this patient. After this combined therapy for 25 weeks and terbinafine monotherapy for additional 12 weeks, the patient was cured. These findings indicate for the first time that terbinafine and amphotericin B are synergistic in killing F. nubica both in vitro and in vivo.