Mapping the single-cell landscape of acral melanoma and analysis of the molecular regulatory network of the tumor microenvironments.

Acral melanoma (AM) exhibits a high incidence in Asian patients with melanoma, and it is not well treated with immunotherapy. However, little attention has been paid to the characteristics of the immune microenvironment in AM. Therefore, in this study, we collected clinical samples from Chinese patients with AM and conducted single-cell RNA sequencing to analyze the heterogeneity of its tumor microenvironments (TMEs) and the molecular regulatory network. Our analysis revealed that genes, such as TWIST1, EREG, TNFRSF9, and CTGF could drive the deregulation of various TME components. The molecular interaction relationships between TME cells, such as MIF-CD44 and TNFSF9-TNFRSF9, might be an attractive target for developing novel immunotherapeutic agents.

Acral melanoma is a type of cancer that affects the hands and feet. It tends to form on the palms, soles, and under the nails. It is rare in people of European descent, but in Asian populations it makes up more than half of all melanoma cases. Unlike other types of skin cancer, it does not respond well to immunotherapy, but scientists did not understand why. Historically, cancer research has focused on the genetics of whole tumors. But cancer is complicated. Malignant cells recruit other cells to help them survive and grow, and to protect them from attacks by the immune system. Together, they create their own ecosystem, called the tumor microenvironment. The exact makeup of the tumor microenvironment differs depending on the type of cancer and on the genetics of the individual. Investigating the cells that 'support' the tumor could help to explain how acral melanoma develops and why it does not respond to treatment. To address these questions, He et al. collected samples from six patients with acral melanoma and examined the genes used by more than 60,000 individual cells. This revealed nine different types of cells in the tumor microenvironment. Most were cancer cells, but there were also immune cells, blood vessel cells, skin cells, and a type of cell that makes connective tissue. He et al. also identified four genes that most likely shape the tumor microenvironment, and two gene pairs that may control some of the interactions between the cells. Investigating these early findings in more detail could open new treatment avenues for acral melanoma. The number of samples in this study was small, but it provides a starting point for future investigation. With more data, researchers could start to develop treatments that target the unique tumor microenvironment of this type of cancer.

Construction of competing endogenous RNA interaction network as prognostic markers in metastatic melanoma.

Malignant melanoma (MM) is a malignant tumor originating from melanocytes, with high aggressiveness, high metastasis and extremely poor prognosis. MM accounts for 4% of skin cancers and 80% of mortality, and the median survival of patients with metastatic melanoma is only about 6 months, with a five-year survival rate of less than 10%. In recent years, the incidence of melanoma has gradually increased and has become one of the serious diseases that endanger human health. Competitive endogenous RNA (ceRNA) is the main model of the mechanism by which long chain non-coding RNAs (lncRNAs) play a regulatory role in the disease. LncRNAs can act as a "sponge", competitively attracting small RNAs (micoRNAs; miRNAs), thus interfering with miRNA function, and affect the expression of target gene messenger RNAs (mRNAs), ultimately promoting tumorigenesis and progression. Bioinformatics analysis can identify potentially prognostic and therapeutically relevant differentially expressed genes in MM, finding lncRNAs, miRNAs and mRNAs that are interconnected through the ceRNA network, providing further insight into gene regulation and prognosis of metastatic melanoma. Weighted co-expression networks were used to identify lncRNA and mRNA modules associated with the metastatic phenotype, as well as the co-expression genes contained in the modules. A total of 17 lncRNAs, six miRNAs, and 11 mRNAs were used to construct a ceRNA interaction network that plays a regulatory role in metastatic melanoma patients. The prognostic risk model was used as a sorter to classify the survival prognosis of melanoma patients. Four groups of ceRNA interaction triplets were finally obtained, which miR-3662 might has potential implication for the treatment of metaststic melanoma patients, and futher experiments confirmed the regulating relationship and phenotype of this assumption. This study provides new targets to regulate metastatic process, predict metastatic potential and indicates that the miR-3662 can be used in the treatment of melanoma.

Hydrilla verticillata-Sulfur-Based Heterotrophic and Autotrophic Denitrification Process for Nitrate-Rich Agricultural Runoff Treatment.

Hydrilla verticillata-sulfur-based heterotrophic and autotrophic denitrification (HSHAD) process was developed in free water surface constructed wetland mesocosms for the treatment of nitrate-rich agricultural runoff with low chemical oxygen demand/total nitrogen (C/N) ratio, whose feasibility and mechanism were extensively studied and compared with those of H. verticillata heterotrophic denitrification (HHD) mesocosms through a 273-day operation. The results showed that the heterotrophic and autotrophic denitrification can be combined successfully in HSHAD mesocosms, and achieve satisfactory nitrate removal performance. The average NO3--N removal efficiency and denitrification rate of HSHAD were 94.4% and 1.3 g NO3--N m-3·d-1 in steady phase II (7-118 d). Most nitrate was reduced by heterotrophic denitrification with sufficient organic carbon in phase I (0-6 d) and II, i.e., the C/N ratio exceeded 4.0, and no significant difference of nitrate removal capacity was observed between HSHAD and HHD mesocosms. During phase III (119-273 d), sulfur autotrophic denitrification gradually dominated the HSHAD process with the C/N ratio less than 4.0, and HSHAD mesocosms obtained higher NO3--N removal efficiency and denitrification rate (79.1% and 1.1 g NO3--N m-3·d-1) than HHD mesocosms (65.3% and 1.0 g NO3--N m-3·d-1). As a whole, HSHAD mesocosms removed 58.8 mg NO3--N more than HHD mesocosms. pH fluctuated between 6.9-9.0 without any pH buffer. In general, HSHAD mesocosms were more stable and efficient than HHD mesocosms for NO3--N removal from agricultural runoff during long-term operation. The denitrificans containing narG (1.67 × 108 ± 1.28 × 107 copies g-1 mixture-soil-1), nirS (8.25 × 107 ± 8.95 × 106 copies g-1 mixture-soil-1), and nosZ (1.56 × 106 ± 1.60 × 105 copies g-1 mixture-soil-1) of litter bags and bottoms in HSHAD were higher than those in HHD, which indicated that the combined heterotrophic and autotrophic denitrification can increase the abundance of denitrificans containing narG, nirS, and nosZ, thus leading to better denitrification performance.

Influence of Carrier Filling Ratio on the Advanced Nitrogen Removal from Wastewater Treatment Plant Effluent by Denitrifying MBBR.

The filling ratio (FR) of a carrier has an influence on the pollutant removal of the aerobic moving bed biofilm reactor (MBBR). However, the effect of the polyethylene (PE) carrier FR on the performance and microbial characteristics of the denitrifying MBBR for the treatment of wastewater treatment plant (WWTP) effluent has not been extensively studied. A bench-scale denitrifying MBBR was set up and operated with PE carrier FRs of 20%, 30%, 40%, and 50% for the degradation of chemical oxygen demand (COD) and nitrogen from WWTP effluent at 12 h hydraulic retention time (HRT). The nitrate removal rates with FRs of 20%, 30%, 40%, and 50% were 94.3 ± 3.9%, 87.7 ± 7.3%, 89.7 ± 11.6%, and 94.6 ± 4.0%, and the corresponding denitrification rates (rNO3--N) were 8.0 ± 5.6, 11.3 ± 4.6, 11.6 ± 4.6, and 10.0 ± 4.9 mg NO3--N/L/d, respectively. Nitrous oxide reductase (nosZ) gene-based terminal restriction fragment length polymorphism (T-RFLP) analysis illustrated that the highest functional diversity (Shannon's diversity index, H') of biofilm microbial community was obtained at 30% FR. The quantitative polymerase chain reaction (qPCR) results indicated that the abundance of nitrate reductase (narG) and nosZ genes at 30% FR was significantly higher than that at 20% FR, and no significant changes were observed at 40% and 50% FRs. Thus, 30% FR was recommended as the optimal carrier FR for the denitrifying MBBR.

Removal of phenanthrene and pyrene from contaminated sandy soil using hydrogen peroxide oxidation catalyzed by basic oxygen furnace slag.

Soil contamination with polycyclic aromatic hydrocarbons (PAHs) is a serious problem in Northeast China, especially in the steel industrial area. The objective of this study was to evaluate the feasibility of using basic oxygen furnace (BOF) slag to activate the Fenton-like remediation of PAH-contaminated soil to achieve the objectives of "waste control by waste" and "resource recycling" in Chinese steel industry. The effects of BOF slag dosages, H2O2 concentrations, and exothermicity-driven evaporation were evaluated with respect to the removal efficiencies of phenanthrene (Phe) and pyrene (Pyr). Results indicated that PAH oxidation was proportional to the BOF slag dosages and was increased exponentially with H2O2 concentrations. Evaporation due to increasing temperature caused by exothermic reaction played an important role in total soil PAH losses. The sequential Fenton-like oxidation with a 3-times application of 15% H2O2 and the same BOF slag repeatedly used were able to remove 65.87% of Phe and 58.33% of Pyr, respectively. Soluble iron oxides containing in BOF slag were reduced, while amorphous iron oxide concentration remained stable during the repeated Fenton-like process. Column study mimics real field applications showing high removal efficiencies of Phe (36.05-83.20%) and Pyr (21.79-68.06%) in 30-cm depth of soil profile. The tests on soluble heavy metal concentrations after the reactions with high slag dosage or high H2O2 concentration confirmed that BOF slag would not cause heavy metal contamination. Consequently, BOF slag may provide an efficient way for enhancing the Fenton-like based remediation of heavily PAH-polluted soil with little risk on collateral heavy metal contamination. However, an external gas collection and purification equipment would be essential to eliminate the evaporated PAHs.

Simultaneous removal of Cd(II) and Sb(V) by Fe-Mn binary oxide: Positive effects of Cd(II) on Sb(V) adsorption.

The coexistence of cadmium ion (Cd(II)) and antimonate (Sb(V)) creates the need for their simultaneous removal. This study aims to investigate the effects of positively-charged Cd(II) on the removal of negative Sb(V) ions by Fe-Mn binary oxide (FMBO) and associated mechanisms. The maximum Sb(V) adsorption density (Qmax,Sb(V)) increased from 1.02 to 1.32 and 2.01 mmol/g in the presence of Cd(II) at 0.25 and 0.50 mmol/L. Cd(2+) exhibited a more significant positive effect than both calcium ion (Ca(2+)) and manganese ion (Mn(2+)). Cd(2+) showed higher affinity towards FMBO and increased its ζ-potential more significantly compared to Ca(2+) and Mn(2+). The simultaneous adsorption of Sb(V) and Cd(II) onto FMBO can be achieved over a wide initial pH (pHi) range from 2 to 9, and QSb(V) decreases whereas QCd(II) increases with elevated pHi. Their combined values, as expressed by QSb(V)+Cd(II), amount to about 2 mmol/g and vary slightly in the pHi range 4-9. FTIR and XPS spectra indicate the significant synergistic effect of Cd(II) on Sb(V) adsorption onto FMBO, and that little chemical valence transformation occurs. These results may be valuable for the treatment of wastewater with coexisting heavy metals such as Cd(II) and Sb(V).

Adsorption of antimony(V) onto Mn(II)-enriched surfaces of manganese-oxide and FeMn binary oxide.

Manganese(IV) oxide [Mn(IV)] potentially oxidizes antimony(III) [Sb(III)] to antimony(V) [Sb(V)] and improves Sb removal by FeMn binary oxide (FMBO) through an oxidation-adsorption mechanism. This study focused on the effect of Mn(IV) reductive dissolution by potassium sulfite (K2SO3) on Sb(V) adsorption onto manganese oxide (Mn-oxide) and FMBO. The maximum Sb(V) adsorption (Qmax,Sb(V)) increased from 1.0 to 1.1 mmol g(-1) for FMBO and from 0.4 to 0.6 mmol g(-1) for Mn-oxide after pretreatment with 10 mmol L(-1) K2SO3. The addition of 2.5 mmol L(-1) Mn(2+) also significantly improved Sb(V) adsorption, and the observed Qmax,Sb(V) increased to 1.4 and 1.0 mmol g(-1) for FMBO and Mn-oxide, respectively, with pre-adsorbed Mn(2+). Neither K2SO3 nor Mn(2+) addition had any effect on Sb(V) adsorption onto iron oxide (Fe-oxide). Mn(2+) introduced by either Mn(IV) dissolution or addition tended to form outer-sphere surface complexes with hydroxyl groups on Mn-oxide surfaces (MnOOH). Mn(2+) at 2.5 mmol L(-1) shifted the isoelectric point (pHiep) from 7.5 to 10.2 for FMBO and from 4.8 to 9.2 for Mn-oxide and hence benefited Sb(V) adsorption. The adsorption of Sb(V) onto Mn(2+)-enriched surfaces contributed to the release of Mn(2+), and the X-ray photoelectron spectra also indicated increased binding energy of Mn 2p3/2 after the adsorption of Sb(V) onto K2SO3-pretreated FMBO and Mn-oxide. Sb(V) adsorption involved the formation of inner-sphere complexes and contributed to the release of Mn(2+). In the removal of Sb(III) by Mn-based oxides, the oxidation of Sb(III) to Sb(V) by Mn(IV) oxides had an effect; however, Mn(IV) dissolution and Mn(2+)-enrichment also played an important role.

Effects of fluoride on the removal of cadmium and phosphate by aluminum coagulation.

This study focuses on the effects of pH and fluoride at different molar ratios of fluoride to Al (RF:Al) on the removal of cadmium (Cd2+) and phosphate by Al coagulation. Fluoride at RF:Al≥3:1 inhibits the removal of Cd over wide Al dose ranges from 5 to 10 mg/L as Al. The removal of phosphate decreases significantly at high RF:Al of 10:1 whereas at lowered RF:Al (i.e., ≤6:1), an adverse effect is observed only at insufficient Al doses below 2 mg/L. Fluoride shows inhibitive effects towards the removal of Cd at pH7 and 8 and that of phosphate at pH6. Fluoride decreases the ζ-potential in both systems, and the decreasing extent is positively correlated to the elevated RF:Al. The Al fluoride interactions include the formation of Al-F complexes and the adsorption of fluoride onto Al(OH)3 precipitates, i.e., the formation of Al(OH)nFm. Al-F complex formation inhibits Al hydrolysis and increases residual Al levels, and a more significant increase was observed at lower pH. Al-F complexes at high RF:Al complicate the coagulation behavior of Al towards both negative and positive ionic species. Moreover, fluoride at low RF:Al shows little effect on Al coagulation behavior towards Cd2+ and phosphate, and the spent defluoridation adsorbent, i.e., aluminum (Al) hydro(oxide) with adsorbed fluoride at RF:Al of below 0.1:1, may be reclaimed as a coagulant after being dissolved.

Longer rest intervals do not attenuate the superior effects of accumulated exercise on arterial stiffness.

PURPOSE: To examine and compare the acute effects of moderate-intensity continuous and accumulated exercise in three bouts with different intervals on arterial stiffness. METHOD: Nineteen healthy young males (mean age = 24.7 years) were randomized to no-exercise control (CON), continuous exercise (CE, 30-min cycling), accumulated exercise with 10-min intervals (AE10, 3 × 10-min cycling, 10-min interval), and accumulated exercise with 60-min intervals (AE60, 3 × 10-min cycling, 60-min interval) trial in balanced self-control crossover design. The intensity in all the exercise trials was set at 50% heart rate reserve. Cardio-ankle vascular index (CAVI), an index of arterial stiffness, was measured at baseline (BL), immediately after (0 min) and 60 min after the completion of the exercise. RESULTS: CAVI remained stable (6.8 ± 0.1, 6.8 ± 0.2, 6.9 ± 0.1 at BL, 0 and 60 min, respectively) in CON trial. Immediately after exercise, CAVI in CE, AE10 and AE60 trials all decreased significantly to similar degree compared to CON trial (P < 0.05 for CE, AE10 and AE60 vs. CON). Though CAVI in CE trial returned to baseline level after 60 min of recovery, CAVI in both AE10 and AE60 trials remained significantly low compared to CON trial (P < 0.01 for AE10 and AE60 vs. CON). CONCLUSION: When the total duration and relative intensity were matched, the effects of accumulated exercise in three bouts were superior to continuous exercise. Elongation of intervals between bouts did not attenuate the superior effects of accumulated exercise on arterial stiffness. TRIAL REGISTRATION: ChiCTR-OTRCC-14005229.

Adsorption of Sb(III) and Sb(V) on Freshly Prepared Ferric Hydroxide (FeOxHy).

This study prepared fresh ferric hydroxide (in-situ FeOxHy) by the enhanced hydrolysis of Fe3+ ions, and investigates its adsorptive behaviors toward Sb(III) and Sb(V) through laboratory and pilot-scale studies. A contact time of 120-min was enough to achieve adsorption equilibrium for Sb(III) and Sb(V) on the in-situ FeOxHy, and the Elovich model was best to describe the adsorption kinetics of Sb(III) and Sb(V). The Freundlich model was better than Langmuir model to describe the adsorption of Sb(III) and Sb(V) on the in-situ FeOxHy, and the maximum adsorption capacity of Sb(III) and Sb(V) was determined to be 12.77 and 10.21 mmol/g the in-situ FeOxHy as Fe, respectively. Adsorption of Sb(V) decreased whereas that of Sb(III) increased with elevated pH over pH 3-10, owing to the different electrical properties of Sb(III) and Sb(V). Adsorption of Sb(III) and Sb(V) was slightly affected by ionic strength, and thus indicated the formation of inner sphere complexes between Sb and the adsorbent. Sulfate and carbonate showed little effect on the adsorption of Sb(III) and Sb(V). Phosphate significantly inhibited the adsorption of Sb(V), whereas slightly effected that of Sb(III) due to its similar chemical structure to Sb(V). Pilot-scale continuous experiment indicated the feasibility of using in-situ FeOxHy to remove Sb(V), and equilibrium adsorption capacity at the equilibrium Sb(V) concentration of 10 µg/L was determined to be 0.11, 0.07, 0.07, 0.11, and 0.12 mg/g the in-situ FeOxHy as Fe at equilibrium pH of 7.5-7.7, 6.9-7.0, 6.3-6.6, 5.9-6.4, and 5.2-5.9, respectively.