Mesenchymal stromal cells plus basiliximab improve the response of steroid-refractory acute graft-versus-host disease as a second-line therapy: a multicentre, randomized, controlled trial.

BACKGROUND: For patients with steroid-refractory acute graft-versus-host disease (SR-aGVHD), effective second-line regimens are urgently needed. Mesenchymal stromal cells (MSCs) have been used as salvage regimens for SR-aGVHD in the past. However, clinical trials and an overall understanding of the molecular mechanisms of MSCs combined with basiliximab for SR-aGVHD are limited, especially in haploidentical haemopoietic stem cell transplantation (HID HSCT). METHODS: The primary endpoint of this multicentre, randomized, controlled trial was the 4-week complete response (CR) rate of SR-aGVHD. A total of 130 patients with SR-aGVHD were assigned in a 1:1 randomization schedule to the MSC group (receiving basiliximab plus MSCs) or control group (receiving basiliximab alone) (NCT04738981). RESULTS: Most enrolled patients (96.2%) received HID HSCT. The 4-week CR rate of SR-aGVHD in the MSC group was obviously better than that in the control group (83.1% vs. 55.4%, P = 0.001). However, for the overall response rates at week 4, the two groups were comparable. More patients in the control group used ≥ 6 doses of basiliximab (4.6% vs. 20%, P = 0.008). We collected blood samples from 19 consecutive patients and evaluated MSC-derived immunosuppressive cytokines, including HO1, GAL1, GAL9, TNFIA6, PGE2, PDL1, TGF-ß and HGF. Compared to the levels before MSC infusion, the HO1 (P = 0.0072) and TGF-ß (P = 0.0243) levels increased significantly 1 day after MSC infusion. At 7 days after MSC infusion, the levels of HO1, GAL1, TNFIA6 and TGF-ß tended to increase; however, the differences were not statistically significant. Although the 52-week cumulative incidence of cGVHD in the MSC group was comparable to that in the control group, fewer patients in the MSC group developed cGVHD involving ≥3 organs (14.3% vs. 43.6%, P = 0.006). MSCs were well tolerated, no infusion-related adverse events (AEs) occurred and other AEs were also comparable between the two groups. However, patients with malignant haematological diseases in the MSC group had a higher 52-week disease-free survival rate than those in the control group (84.8% vs. 65.9%, P = 0.031). CONCLUSIONS: For SR-aGVHD after allo-HSCT, especially HID HSCT, the combination of MSCs and basiliximab as the second-line therapy led to significantly better 4-week CR rates than basiliximab alone. The addition of MSCs not only did not increase toxicity but also provided a survival benefit.

Flexible Aluminum-Air Battery Based on High-Performance Three-Dimensional Dual-Network PVA/KC/KOH Composite Gel Polymer Electrolyte.

With a large theoretical capacity and high energy density, aluminum-air batteries are a promising energy storage device. However, the rigid structure and liquid electrolyte of a traditional aluminum-air battery limit its application potential in the field of flexible electronics, and the irreversible corrosion of its anode greatly reduces the battery life. To solve the above problems, a PVA/KC/KOH (2 M) composite gel polymer electrolyte (GPE) with a three-dimensional dual-network structure consisting of polyvinyl alcohol (PVA), kappa-carrageenan (KC), and potassium hydroxide was prepared in this paper by a simple two-step method and applied in aluminum-air batteries. At room temperature, the ionic conductivity of the PVA/KC/KOH (2 M) composite GPE was found to be up to 6.50 × 10-3 S cm-1. By utilizing this composite GPE, a single flexible aluminum-air battery was assembled and achieved a maximum discharge voltage of 1.2 V at 5 mA cm-2, with discharge time exceeding 3 h. Moreover, the single flexible aluminum-air battery maintains good electrochemical performance under various deformation modes, and the output voltage of the battery remains at about 99% after 300 cycles. The construction of flexible aluminum-air batteries based on a three-dimensional dual-network PVA/KC/KOH composite GPE provides excellent safety and high-multiplication capabilities for aluminum-air batteries, making them potential candidates for various flexible device applications.

A Comprehensive Study to Determine the Residual Elimination Pattern of Major Metabolites of Amoxicillin-Sulbactam Hybrid Molecules in Rats by UPLC-MS/MS.

Amoxicillin and sulbactam are widely used in animal food compounding. Amoxicillin-sulbactam hybrid molecules are bicester compounds made by linking amoxicillin and sulbactam with methylene groups and have good application prospects. However, the residual elimination pattern of these hybrid molecules in animals needs to be explored. In the present study, the amoxicillin-sulbactam hybrid molecule (AS group) and a mixture of amoxicillin and sulbactam (mixture group) were administered to rats by gavage, and the levels of the major metabolites of amoxicillin, amoxicilloic acid, amoxicillin diketopiperazine, and sulbactam were determined by UPLC-MS/MS. The residue elimination patterns of the major metabolites in the liver, kidney, urine, and feces of rats in the AS group and the mixture group were compared. The results showed that the total amount of amoxicillin, amoxicilloic acid, amoxicillin diketopiperazine, and the highest concentration of sulbactam in the liver and kidney samples of the AS group and the mixture group appeared at 1 h after drug withdrawal. Between 1 h and 12 h post discontinuation, the total amount of amoxicillin, amoxicilloic acid, and amoxicillin diketopiperazine in the two tissues decreased rapidly, and the elimination half-life of the AS group was significantly higher than that in the mixture group (p < 0.05); the residual amount of sulbactam also decreased rapidly, and the elimination half-life was not significantly different (p > 0.05). In 72 h urine samples, the total excretion rates were 60.61 ± 2.13% and 62.62 ± 1.73% in the AS group and mixture group, respectively. The total excretion rates of fecal samples (at 72 h) for the AS group and mixture group were 9.54 ± 0.26% and 10.60 ± 0.24%, respectively. These results showed that the total quantity of amoxicillin, amoxicilloic acid, and amoxicillin diketopiperazine was eliminated more slowly in the liver and kidney of the AS group than those of the mixture group and that the excretion rate through urine and feces was essentially the same for both groups. The residual elimination pattern of the hybrid molecule in rats determined in this study provides a theoretical basis for the in-depth development and application of hybrid molecules, as well as guidelines for the development of similar drugs.

Synergism with Shikimic Acid Restores ß-Lactam Antibiotic Activity against Methicillin-Resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) has evolved into a dangerous pathogen resistant to beta-lactam antibiotics (BLAs) and has become a worrisome superbug. In this study, a strategy in which shikimic acid (SA), which has anti-inflammatory and antibacterial activity, is combined with BLAs to restart BLA activity was proposed for MRSA treatment. The synergistic effects of oxacillin combined with SA against oxacillin resistance in vitro and in vivo were investigated. The excellent synergistic effect of the oxacillin and SA combination was confirmed by performing the checkerboard assay, time-killing assay, live/dead bacterial cell viability assay, and assessing protein leakage. SEM showed that the cells in the control group had a regular, smooth, and intact surface. In contrast, oxacillin and SA or the combination treatment group exhibited different degrees of surface collapse. q-PCR indicated that the combination treatment group significantly inhibited the expression of the mecA gene. In vivo, we showed that the combination treatment increased the survival rate and decreased the bacterial load in mice. These results suggest that the combination of oxacillin with SA is considered an effective treatment option for MRSA, and the combination of SA with oxacillin in the treatment of MRSA is a novel strategy.

Application of Miscanthus substrates in the cultivation of Ganoderma lingzhi.

Ganoderma lingzhi is a traditional Chinese medicine that has been used to improve health and longevity for thousands of years. It is usually cultivated on hardwood log- or sawdust-based formulations. Conversely, in this study, we used Miscanthus sacchariflorus (MSF), M. floridulus, and M. sinensis (MSS), fast-growing perennial grasses widely distributed in China, for G. lingzhi cultivation. Mycelial growth rate, activities of lignin-degrading enzymes on colonized mushroom substrates, and expression levels of CAZymes and laccase genes based on different substrates were analyzed. Total triterpenoids, sterols, and polysaccharides content of fruiting bodies obtained from different substrates were investigated. The activities of laccase and manganese peroxidase in mycelia increased in the MSF- and MSS-based formulations compared with that in the sawdust-based formulation. The results of mycelial growth- and cultivation-related experiments showed that the Miscanthus substrates could be used as the substrates for cultivating G. lingzhi. The content of active ingredients, namely triterpenoids, sterols, and polysaccharides, in fruiting bodies cultivated on the Miscanthus substrates did not decrease compared with those in substrate obtained from the sawdust-based formulation. Therefore, the present study provides alternative substrates for the cultivation of G. lingzhi, and a reference for better utilization of inexpensive substrate in future.

Transcription factors: switches for regulating growth and development in macrofungi.

Macrofungi (or mushrooms) act as an extraordinarily important part to human health due to their nutritional and/or medicinal value, but the detailed researches in growth and development mechanisms have yet to be explored further. Transcription factors (TFs) play indispensable roles in signal transduction and affect growth, development, and metabolism of macrofungi. In recent years, increasing research effort has been employed to probe the relationship between the development of macrofungi and TFs. Herein, the present review comprehensively summarized the functional TFs researched in macrofungi, including modulating mycelial growth, fructification, sclerotial formation, sexual reproduction, spore formation, and secondary metabolism. Meanwhile, the possible effect mechanisms of TFs on the growth and development of some macrofungi were also revealed. Specific examples of functional characterizations of TFs in macrofungi (such as Schizophyllum commune and Coprinopsis cinerea) were described to a better comprehension of regulatory effect. Future research prospects in the field of TFs of macrofungi are discussed. We illustrated the functional versatility of the TFs in macrofungi based on specific examples. A systematical realization of the interaction and possible mechanisms between TFs and macrofungi can supply possible solutions to regulate genetic characteristics, which supply novel insights into the regulation of growth, development and metabolism of macrofungi. KEY POINTS: • The functional TFs researched in macrofungi were summarized. • The possible effect mechanisms of TFs in macrofungal were described. • The multiple physiological functions of TFs in macrofungi were discussed.

Relationship between antioxidant enzymes and sclerotial formation of Pleurotus tuber-regium under abiotic stress.

In order to explore the relationship between sclerotial formation and antioxidant enzymes under abiotic stresses, the effects of abiotic stresses including temperature, pH value, osmotic pressure, limited nitrogen, and hydrogen peroxide (H2O2) on the activities of antioxidant enzymes, ascorbate peroxidase (APX), superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) in Pleurotus tuber-regium were studied. Meanwhile, the sclerotial formation under these abiotic stress conditions was also investigated. It was found that low temperature, weak alkaline, appropriate osmotic stress, and H2O2 can promote sclerotial formation, and sclerotial formation always tended to occur when the activities of antioxidant enzymes were at a high value. During the prolonged low temperature stress, SOD acted mainly in the early stage of stress, while POD and CAT had higher activity in the middle and late stage. Moreover, the reverse transcription quantitative polymerase chain reaction (RT-qPCR) results showed that SOD.193 and POD.535 were significantly down-regulated in sclerotia, and CAT.1115 and POD.401 were up-regulated instead. These antioxidant enzyme genes played an important role in the sclerotial formation under low temperature stress. It is strongly suggested that antioxidant enzymes and abiotic stresses are closely related to sclerotial formation in P. tuber-regium. KEY POINTS: • Low temperature and H2O2 can promote sclerotial formation. • Sclerotia are more likely to form under high antioxidant enzyme activity. • POD.401, POD.535, SOD.193, and CAT.1115 are important for sclerotial formation.

Is serum hemoglobin level an independent prognostic factor for IgA nephropathy?: a systematic review and meta-analysis of observational cohort studies.

BACKGROUND: Decreased serum hemoglobin (Hb) level is associated with Immunoglobulin A nephropathy (IgAN) progression. However, whether serum Hb level is an independent prognostic factor of IgAN remains controversial. Herein, we aimed to investigate the prognostic value of serum Hb level in IgAN. METHODS: The Cochrane Library, Embase, PubMed and Open Grey databases were systematically searched and reviewed. Kidney disease progression of IgAN was defined as a doubling of serum creatinine (SCr), a 30% reduction in estimated glomerular filtration rate (eGFR), end-stage renal disease (ESRD), or death. We evaluated the hazard ratio (HR) between serum Hb level and the incidence of kidney disease progression in IgAN before and after adjusting for relevant covariates. RESULTS: We included nine studies with 10006 patients in the meta-analysis. As a continuous variable, we found that serum Hb was an independent prognostic factor of IgAN [unadjusted HR = 0.89, 95% confidence interval (CI) = 0.84-0.95, I2 = 98%; adjusted HR = 0.85, 95% CI = 0.79-0.91, I2 = 0%]. The sensitivity analysis confirmed the stability of these results. Consistently, as a dichotomous variable defined as the below/above cutoff for anemia, we observed a positive correlation between serum Hb and kidney disease progression in IgAN (unadjusted HR = 2.12, 95% CI = 1.44-3.12, I2 = 79%; adjusted HR = 1.65, 95% CI = 1.20-2.27, I2 = 0%). CONCLUSION: Serum Hb level was independently correlated with the incidence of kidney disease progression in IgAN.

Design, synthesis, and antitumor evaluation of trimethoxyflavonoid with arylurea structure against hepatocellular carcinoma.

Simultaneous targeting of tumor vasculature and inhibitors of tumor cell glycolysis may be a promising antitumor strategy. Here, we reported the total synthesis and biological evaluation of A-ring arylurea flavonoid derivatives with B-ring trimethoxy group, which exhibited potent antitumor activity against a variety of tumor cells in vitro. Most of the derivatives showed in vitro antitumor activity on HepG-2, HGC-27, MDA-MB-231, and A549 cells. Among them, compounds 8e, 8f, 8g, 8h, 8j, and 8l also exhibited significant anti-proliferation effects on liver tumor cell subtypes BEL-7402 and SMMC-7721. Compound 8l had the lowest IC50 value (5.61 ± 0.39 µM) on HepG-2 cells, and showed the effects of inhibiting colony formation, arresting the cell cycle in G0 /G1 phase, and inducing apoptosis in a concentration-dependent manner. In addition, the toxicity of compound 8l on human normal cells LO2 and GES-1 was lower than that of sorafenib. The inhibitory effects of compound 8l on the expression of glycolytic rate-limiting enzymes HKII, PFK-1, PKM2 and vascular endothelial growth factor were further evaluated. Corresponding reduction in intracellular lactate was also detected after compound 8 treatment. Our results support an antitumor strategy targeting tumor vasculature and glycolysis to discover and develop a new generation of antitumor drugs.

Comparative transcriptome analysis revealed candidate genes involved in fruiting body development and sporulation in Ganoderma lucidum.

Ganoderma lucidum is an edible mushroom highly regarded in the traditional Chinese medicine. To better understand the molecular mechanisms underlying fruiting body development in G. lucidum, transcriptome analysis based on RNA sequencing was carried out on different developmental stages: mycelium (G1); primordium (G2); young fruiting body (G3); mature fruiting body (G4); fruiting body in post-sporulation stage (G5). In total, 26,137 unigenes with an average length of 1078 bp were de novo assembled. Functional annotation of transcriptomes matched 72.49% of the unigenes to known proteins available in at least one database. Differentially expressed genes (DEGs) were identified between the evaluated stages: 3135 DEGs in G1 versus G2; 120 in G2 versus G3; 3919 in G3 versus G4; and 1012 in G4 versus G5. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of DEGs identified in G1 versus G2 revealed that, in addition to global and overview maps, enriched pathways were related to amino acid metabolism and carbohydrate metabolism. In contrast, DEGs identified in G2 versus G3 were mainly assigned to the category of metabolism of amino acids and their derivatives, comprising mostly upregulated unigenes. In addition, highly expressed unigenes associated with the transition between different developmental stages were identified, including those encoding hydrophobins, cytochrome P450s, extracellular proteases, and several transcription factors. Meanwhile, highly expressed unigenes related to meiosis such as DMC1, MSH4, HOP1, and Mek1 were also analyzed. Our study provides important insights into the molecular mechanisms underlying fruiting body development and sporulation in G. lucidum.

Alternative oxidase is involved in oxidative stress resistance and melanin synthesis in Annulohypoxylon stygium, a companion fungus of Tremella fuciformis.

Annulohypoxylon stygium, a companion fungus of Tremella fuciformis, provides nutrition for growth and development of T. fuciformis. Alternative oxidase (AOX), which is the terminal oxidase of the alternative respiration pathway, functions to transfer electrons from ubiquinol to O2 with the production of H2O. In this study, an AOX encoded gene, Asaox, was cloned from A. stygium. The coding sequence of Asaox gene contains 1056 nucleotides and encodes 351 amino acids. RNA interference was used to study the function of Asaox in A. stygium. The Asaox-silenced strains were confirmed by PCR, quantitative real-time PCR, and Southern blot. The Asaox-silenced strains exhibited increased relative growth inhibition rates when inoculated on PDA plates with 50 mM H2O2, compared with wild-type strain. The growth rate in sawdust medium, melanin content, and laccase activity of Asaox-silenced strains were decreased. The expression levels of tyr and pks genes were decreased in Asaox-silenced strains, indicating that there might be two melanin synthesis pathways, DHN and DOPA, in A. stygium. In summary, the results have demonstrated that Asaox gene was involved in oxidative stress resistance and melanin synthesis in A. stygium.

Prediction of postpartum hemorrhage in pregnant women with immune thrombocytopenia: Development and validation of the MONITOR model in a nationwide multicenter study.

Globally, postpartum hemorrhage (PPH) is the leading cause of maternal death. Women with immune thrombocytopenia (ITP) are at increased risk of developing PPH. Early identification of PPH helps to prevent adverse outcomes, but is underused because clinicians do not have a tool to predict PPH for women with ITP. We therefore conducted a nationwide multicenter retrospective study to develop and validate a prediction model of PPH in patients with ITP. We included 432 pregnant women (677 pregnancies) with primary ITP from 18 academic tertiary centers in China from January 2008 to August 2018. A total of 157 (23.2%) pregnancies experienced PPH. The derivation cohort included 450 pregnancies. For the validation cohort, we included 117 pregnancies in the temporal validation cohort and 110 pregnancies in the geographical validation cohort. We assessed 25 clinical parameters as candidate predictors and used multivariable logistic regression to develop our prediction model. The final model included seven variables and was named MONITOR (maternal complication, WHO bleeding score, antepartum platelet transfusion, placental abnormalities, platelet count, previous uterine surgery, and primiparity). We established an easy-to-use risk heatmap and risk score of PPH based on the seven risk factors. We externally validated this model using both a temporal validation cohort and a geographical validation cohort. The MONITOR model had an AUC of 0.868 (95% CI 0.828-0.909) in internal validation, 0.869 (95% CI 0.802-0.937) in the temporal validation, and 0.811 (95% CI 0.713-0.908) in the geographical validation. Calibration plots demonstrated good agreement between MONITOR-predicted probability and actual observation in both internal validation and external validation. Therefore, we developed and validated a very accurate prediction model for PPH. We hope that the model will contribute to more precise clinical care, decreased adverse outcomes, and better health care resource allocation.

Discovery and development of tumor glycolysis rate-limiting enzyme inhibitors.

Tumor cells mainly provide necessary energy and substances for rapid cell growth through aerobic perglycolysis rather than oxidative phosphorylation. This phenomenon is called the "Warburg effect". The mechanism of glycolysis in tumor cells is more complicated, which is caused by the comprehensive regulation of multiple factors. Abnormal enzyme metabolism is one of the main influencing factors and inhibiting the three main rate-limiting enzymes in glycolysis is thought to be important strategy for cancer treatment. Therefore, numerous inhibitors of glycolysis rate-limiting enzyme have been developed in recent years, such as the latest HKII inhibitor and PKM2 inhibitor Pachymic acid (PA) and N-(4-(3-(3-(methylamino)-3-oxopropyl)-5-(4'-(trifluoromethyl)-[1,1'-biphenyl]-4-yl)-1H-pyrazol-1-yl)phenyl)propiolamide. The review focuses on source, structure-activity relationship, bioecological activity and mechanism of the three main rate-limiting enzymes inhibitors, and hopes to guide the future research on the design and synthesis of rate-limiting enzyme inhibitors.

Heat stress in macrofungi: effects and response mechanisms.

Temperature is one of the key factors that affects the growth and development of macrofungi. Heat stress not only negatively affects the morphology and growth rate of macrofungi, but also destroys cell structures and influences cell metabolism. Due to loosed structure of cell walls and increased membrane fluidity, which caused by heat stress, the outflow of intracellular nutrients makes macrofungi more vulnerable to invasion by pathogens. Macrofungi accumulate reactive oxygen species (ROS), Ca2+, and nitric oxide (NO) when heat-stressed, which transmit and amplify the heat stimulation signal through intracellular signal transduction pathways. Through regulation of some transcription factors including heat response factors (HSFs), POZCP26 and MYB, macrofungi respond to heat stress by different mechanisms. In this paper, we present mechanisms used by macrofungi to adapt and survive under heat stress conditions, including antioxidant defense systems that eliminate the excess ROS, increase in trehalose levels that prevent enzymes and proteins deformation, and stabilize cell structures and heat shock proteins (HSPs) that repair damaged proteins and synthesis of auxins, which increase the activity of antioxidant enzymes. All of these help macrofungi resist and adapt to heat stress. KEY POINTS: • The effects of heat stress on macrofungal growth and development were described. • The respond mechanisms to heat stress in macrofungi were summarized. • The further research directions of heat stress in macrofungi were discussed.

[Rapid and simultaneous determination of 10 active components of Psoraleae Fructus in beagle dog plasma using UPLC-MS/MS and its application in pharmacokinetic study].

An UPLC-MS/MS method for rapid and simultaneous determination of psoralen, isopsoralen, apigenin, genistein, bavaisoflavone, neobavaisoflavone, bavachin, bavachinin, psoralenoside, and isopsoralenoside of Psoraleae Fructus in beagle dog plasma was established, and then the method was applied in the pharmacokinetic study after oral administration of Psoraleae Fructus extract to beagle dogs. The pharmacokinetic parameters were calculated by the software of WinNonlin. A Waters HSS-T3 column(2.1 mm×100 mm,1.8 µm)was used for liquid chromatography separation with acetonitrile-water(containing 0.004% formic acid) as the mobile phase for gradient elution.The mass spectrometry was detected using electrospray ion source(ESI) under multi-reaction monitoring mode(MRM), as well as positive ion mode. Analysis time only takes 8.5 min. The methodological study in terms of specificity, accuracy, precision, linear range, recovery, matrix effect, and stability, was validated. The LC-MS analysis method established in this experiment was simple, specific, accurate, reliable, and meet the requirement of pharmacokinetic study in plasma after administration of Psoraleae Fructus extract to beagle dogs. Six beagle dogs received intragastric administration of Psoraleae Fructus extract, T_(max) of 10 chemical components is 1.92-5.67 h; among them, C_(max) of psoralen, isopsoralen, psoralenoside and isopsoralenoside is 383-3 613 ng·mL~(-1), and AUC_(0-∞) is 3 556-18 949 ng·h·mL~(-1), t_(1/2) is 2.45-4.83 h. C_(max) of the remaining six compounds is 0.81-19.9 ng·mL~(-1), AUC_(0-∞ )is 6.54-178 ng·h·mL~(-1), t_(1/2) is 2.95-7.29 h. The UPLC-MS/MS analysis method established in this study was proved to be accurate and sensitive that it can be applied to the pharmacokinetic study of beagle dogs after oral administration of Psoraleae Fructus extract.

Rational 3D Coiled Morphology for Efficient Solar-Driven Desalination.

Aiming at the global water scarcity, solar-driven desalination based on photothermal materials is identified as a promising strategy for freshwater production because of sustainability, spontaneity, and flexibility. Water transfer in photothermal materials, especially ones with 3D morphologies, can adjust the evaporation efficiency as a critical factor. In this work, a rationally designed roll morphology has been introduced into photothermal to advance the water transfer evaporation via controllable capillary action. The vertical intervals of the roll, similar to slit pore, can pump the water up to the entire materials to not only keep a stable vapor generation rate but reject salt precipitation. Additionally, the roll morphology also improves the light-harvesting via both the high roughness surface and confinement absorption inside the intervals. With excellent water transfer and energy management, photothermal roll showed an evaporation rate up to 1.93 ± 0.05 kg m-2 h-1, which was over 44% higher than the flat sample in the same constituents. Under actual conditions, the freshwater generation rate was achieved up to 1.09 kg m-2 h-1 on average of the whole daylight hours. The work provides novel insights into the design of efficient morphology in photothermal materials and advances their practical applications in sustainable water generation.

Biogenesis of macrofungal sclerotia: influencing factors and molecular mechanisms.

Sclerotia are dense, hard tissue structures formed by asexual reproduction of fungal hyphae in adverse environmental conditions. Macrofungal sclerotia are used in medicinal materials, healthcare foods, and nutritional supplements because of their nutritional value and biologically active ingredients, which are attracting increasing attention. Over the past few decades, the influence of abiotic factors such as nutrition (e.g., carbon and nitrogen sources) and environmental conditions (e.g., temperature, pH), and of the local biotic community (e.g., concomitants) on the formation of macrofungal sclerotia has been studied. The molecular mechanisms controlling macrofungal sclerotia formation, including oxidative stress (reactive oxygen species), signal transduction (Ca2+ channels and mitogen-activated protein kinase pathways), and gene expression regulation (differential expression of important enzyme or structural protein genes), have also been revealed. At the end of this review, future research prospects in the field of biogenesis of macrofungal sclerotia are discussed. KEY POINTS: • We describe factors that influence biogenesis of macrofungal sclerotia. • We explain molecular mechanisms of sclerotial biogenesis. • We discuss future directions of study of macrofungal sclerotia biogenesis.

Internet of Things in Marine Environment Monitoring: A Review.

Marine environment monitoring has attracted more and more attention due to the growing concern about climate change. During the past couple of decades, advanced information and communication technologies have been applied to the development of various marine environment monitoring systems. Among others, the Internet of Things (IoT) has been playing an important role in this area. This paper presents a review of the application of the Internet of Things in the field of marine environment monitoring. New technologies including advanced Big Data analytics and their applications in this area are briefly reviewed. It also discusses key research challenges and opportunities in this area, including the potential application of IoT and Big Data in marine environment protection.

Abnormal expression of serum soluble E-cadherin is correlated with clinicopathological features and prognosis of breast cancer.

BACKGROUND: Increased amounts of soluble E-cadherin (E-cad) have been found in the serum in various cancers, but the role of serum soluble E-cad in the prognosis of breast cancer patients has not been explored in Asian populations. MATERIAL/METHOD: Blood samples from 111 consecutive patients diagnosed with breast cancer and 55 healthy controls were investigated.Serum soluble E-cad expression levels were measured by enzyme-linked immunosorbent assay(ELISA) with an immunoassay kit according to the manufacturer's directions. Kaplan-Meier analyses were used to evaluate the association between serum soluble E-cad expression level and survival. All statistical tests were 2-sided. RESULTS: The serum levels of soluble E-cad in breast cancer patients were significantly higher than those of the control group (2218.9±319.6 ng/ml vs. 742.8±91.7 ng/ml, p<0.001). Serum levels of soluble E-cad correlated significantly with TNM stage (P=0.007), tumor grade (P=0.03), and lymph node metastasis (P<0.001). Kaplan-Meier analysis with the log-rank test indicated that high serum levels of soluble E-cad had a significant impact on overall survival (55.4% vs. 81.4%; P=0.032) and disease-free survival (36.8% vs. 67.8%; P=0.002) in breast cancer. Multivariate analysis revealed that serum levels of soluble E-cad were independently associated with overall survival and disease-free survival in breast cancer patients. CONCLUSIONS: Serum soluble E-cad level is an independent prognostic factor in Asian breast cancer patients.