High Activity Research Articles

Synthesis of Low-Molecular-Weight Fucoidan Analogue and Its Inhibitory Activities against Heparanase and SARS-CoV-2 Infection.

Heparan sulfate (HS) is ubiquitous on cell surfaces and is used as a receptor by many viruses including SARS-CoV-2. However, increased activity of the inflammatory enzyme heparanase (HPSE), which hydrolyses HS, in patients with COVID-19 not only increases the severity of symptoms but also may facilitate the spread of the virus by degrading HS on the cell surface. Therefore, synthetic HPSE blockades, which can bind to SARS-CoV-2 spike protein (SARS-CoV-2-S) and inhibit viral entry, have attracted much attention. This study investigated the development of a new dual-targeting antiviral agent against HPSE and SARS-CoV-2-S using fucoidan as a structural motif. It was found that all-sulfated fucoidan derivative 10, which exhibited the highest binding affinity to SARS-CoV-2-S among 13 derivatives, also showed the highest inhibitory activity against HPSE. Based on this, a newly designed and synthesized fucoidan analogue 16, in which the octyl group of 10 was changed to a cholestanyl group, was found to show approximately 3 times higher activity than 10 but did not inhibit factor Xa associated with undesired anticoagulant effects. The binding affinity of 16 to SARS-CoV-2-S was significantly increased approximately 400-fold over that of 10. The binding of 16 to SARS-CoV-2-S inhibited the binding between SARS-CoV-2-S and heparin and between SARS-CoV-2-S and ACE2. Furthermore, 16 effectively inhibited infection by the SARS-CoV-2 Wuhan strain and two Omicron subvariants.

Priming with multiwalled carbon nanotubes improved biomass accumulation, biological activityand metabolism of four horticultural plants during the sprouting stage.

It is imperative to enhance the quality of sprouts since they are a rich source of various primary and secondary metabolites. The objective of this work was to examine how multiwalled carbon nanotubes (MWCNTs) priming at various concentrations affected the nutritional qualities of four horticultural plants (T. foenum-graecum, L. grandiflorum, L. sativum and A. graveolens) and their sprouting processes. Among the four applied concentrations (10-60 mgL-1), MWCNTs at 10 and 40 mg L⁻¹ induced the highest biomass accumulation in L. grandiflorum and T. foenum-graecum, respectively, while 60 mg L⁻¹ was most effective for L. sativum and A. graveolent. MWCNTs induced growth by enhancing photosynthesis, as shown by increased chlorophyll content and rubisco activity, which rose by 27%, 17%, 23% and 12% in T. foenum-graecum, L. grandiflorum, L. sativum, and A. graveolens, respectively. Enhanced photosynthesis by MWCNTs improved sugar metabolism as indicated by increased activity of sugar metabolic enzymes such as amylase, starch synthase and invertase. This also supplied the carbon necessary for the production of primary (amino acids, fatty acids and organic acids) and secondary (flavonoids and polyphenols) metabolites. There was consistently higher activity of antioxidant enzymes (catalase and peroxidase). Interestingly, species-specific reactions to MWCNT priming were observed, where L. sativum sprouts showed the highest antioxidant activity, followed by A. graveolens. MWCNT priming improves sprout growth and nutritional quality by boosting metabolic processes and antioxidant activity, presenting a promising approach for sustainable agriculture. © 2024 Society of Chemical Industry.

Synthesis of Low‐Molecular‐Weight Fucoidan Analogue and Its Inhibitory Activities against Heparanase and SARS‐CoV‐2 Infection

AbstractHeparan sulfate (HS) is ubiquitous on cell surfaces and is used as a receptor by many viruses including SARS‐CoV‐2. However, increased activity of the inflammatory enzyme heparanase (HPSE), which hydrolyses HS, in patients with COVID‐19 not only increases the severity of symptoms but also may facilitate the spread of the virus by degrading HS on the cell surface. Therefore, synthetic HPSE blockades, which can bind to SARS‐CoV‐2 spike protein (SARS‐CoV‐2‐S) and inhibit viral entry, have attracted much attention. This study investigated the development of a new dual‐targeting antiviral agent against HPSE and SARS‐CoV‐2‐S using fucoidan as a structural motif. It was found that all‐sulfated fucoidan derivative 10, which exhibited the highest binding affinity to SARS‐CoV‐2‐S among 13 derivatives, also showed the highest inhibitory activity against HPSE. Based on this, a newly designed and synthesized fucoidan analogue 16, in which the octyl group of 10 was changed to a cholestanyl group, was found to show approximately 3 times higher activity than 10 but did not inhibit factor Xa associated with undesired anticoagulant effects. The binding affinity of 16 to SARS‐CoV‐2‐S was significantly increased approximately 400‐fold over that of 10. The binding of 16 to SARS‐CoV‐2‐S inhibited the binding between SARS‐CoV‐2‐S and heparin and between SARS‐CoV‐2‐S and ACE2. Furthermore, 16 effectively inhibited infection by the SARS‐CoV‐2 Wuhan strain and two Omicron subvariants.

Isolation, characterization, and analysis of pure compounds from Leea macrophylla leaf extract for antibacterial, antidiabetic, cytotoxicity and phytotoxicity

This research aims to isolate, characterize, and analyze pure compounds from Leea macrophylla leaf extract to investigate its antibacterial, antidiabetic, cytotoxic, and phytotoxic effects. Fresh leaves were collected, dried, and subjected to methanol extraction to obtain a crude extract. From the petroleum ether fraction (PEF) of this extract, three fractions—designated LM1, LM2, and LM3—were prepared using column chromatography. The fractions were tried to be characterized in search for single compound by instrumental technique like ATR-FTIR, 1H NMR and 13C NMR but the 1H NMR and 13C NMR spectra were found complex which were difficult to interpret. To dispel the doubt and get clear idea about the structure, GC-MS analysis of the compounds was carried out whose result showed that all the three extracts were decomposed to several small organic compounds that made the structure elucidation difficult. For this complication, the characterization of the extracts was not possible. Numerous compounds were identified in the methanol extract of L.macrophylla through GC-MS analysis. Among these compounds, Benzene, 1,2,3-trimethyl- and Undecane were found in higher percentages in LM1. LM2 contained Azulene and Bicyclo [4.4.1]undeca-1,3,5,7,9-pentaene, while LM3 was characterized by the presence of 9,9-Dimethoxybicyclo [3.3.1]nona-2,4-dione and 11-(2-Cyclopenten-1-yl)undecanoic acid, among others. The antibacterial activity of these fractions was evaluated against various bacterial strains, demonstrating broad-spectrum effectiveness. LM1 fraction showed the highest antibacterial activity against Proteus sp. With zone of inhibition 25 mm and weak activity against S. sonnei with zone of inhibition 5 mm. LM2 showed the highest activity to both E. cocci and P. aeruginosa with the zone of inhibition of 18 mm and comparatively lower but significant against Proteus sp. LM3 was highly active to S. sonnei with zone of inhibition 20 mm and lower but quite significant against Proteus sp. Moreover, the anti-diabetic potential was assessed, with LM1 showing the strongest α-amylase inhibitory activity, outperforming quercetin (standard). The IC50 values of LM1, LM2, LM3, and quercetin were 57.36 μg/mL, 100.66 μg/mL, 164.92 μg/mL, and 97.45 μg/mL, respectively. In addition, cytotoxicity was assessed using a brine shrimp lethality bioassay, and phytotoxicity was evaluated through seed germination and growth assays. The results suggest that L.macrophylla leaf extracts have potential applications in antimicrobial, antidiabetic, and anti-cancer contexts. This comprehensive study bridges gaps in knowledge surrounding L.macrophylla's multifaceted properties, offering insights into its therapeutic and ecological potential for healthcare and environmental management.

The molecular reactive pathway between lipoxygenase and lipase and reactive species generated in dielectric barrier discharge atmospheric cold plasma: An investigation using molecular docking

The molecular docking was explored to study the interactions between reactive species generated by cold plasma and the enzymes lipoxygenase (LOX) and lipase (LPS), with the aim of elucidating the molecular mechanisms governing these interactions. Molecular docking results suggest that both LOX and LPS are primarily involved in hydrogen bonding interactions with the seven reactive species. The key binding sites for LOX and LPS were identified as Ile 663 and Glu 188, respectively. Notably, the lowest docking energy was observed between LOX and NO (−13.75 kcal/mol), whereas for LPS, it is between LPS and NO3 (−12.08 kcal/mol). Increased treatment voltage and time resulted in higher inactivation levels, with LPS exhibiting higher residual activity compared to LOX. When the voltage was 75 kV and the time was 120 s, the residual activities of LOX and LPS were 42.88% and 56.77%, respectively. Consequently, the results enhance our understanding of the mechanisms underlying the inhibition of enzyme activity by reactive species generated by cold plasma. Moreover, cold plasma may serve as a novel preservation technology for inhibiting lipid oxidation of food by controlling enzyme activity.

Investigation of Novel Isatinylhydantoin Derivatives as Potential Anti-Kinetoplastid Agents.

Neglected tropical diseases are a group of infectious diseases with a high endemicity in developing countries of Africa, Asia, and the Americas. Treatment for these diseases depends solely on chemotherapy, which is associated with severe side effects, toxicity, and the development of parasitic resistance. This highlights a critical need to develop new and effective drugs to curb these diseases. As a result, a series of novel isatinylhydantoin derivatives were synthesized and evaluated for in vitro anti-kinetoplastid activity against seven human- or animal-infective Trypanosoma and two human-infective Leishmania species. The synthesized derivatives were tested for potential cytotoxicity against human, animal, and parasite host-related cell lines. The isatinylhydantoin hybrid 4 b bearing 5-chloroisatin and p-bromobenzyl moieties, showed strong trypanocidal activity against blood-stage T. congolense parasites; however, the promising in vitro trypanocidal potency of 4 b could not be translated to in vivo treatment efficacy in a preliminary animal study. Compounds 5, 2 b, and 5 b, were the most active against amastigotes of L. donovani, showing higher leishmanicidal activity than the reference drug, amphotericin B. These compounds were identified as early antileishmanicidal leads, and future investigations will focus on confirming their antileishmanial potential through in vivo efficacy evaluation as well as their exact mechanism of action.

Enhancing dry sliding wear resistance of high-Mn austenitic steel by adding N

In this study, the wear resistance of two high-Mn austenitic steels, i.e., Fe−18.5Mn−7Cr−0.6C and Fe−18.5Mn−7Cr−0.6C−0.21N was tested in dry sliding friction on a disc friction and wear testing machine (MMU-5G). The wear behavior and microstructure evolution of the two tested steels were investigated. The results revealed that adding N enhanced the wear resistance of high-Mn austenitic steel due to the synergistic effects of hardness, wear hardening, and oxide layer. Interstitial N atoms increased the matrix hardness and decreased the stacking fault energy (SFE). The lower SFE facilitated wear hardening, and the active mechanical twins along with the higher dislocation density induced the formation of a thicker nanocrystalline layer with finer grains. The nanocrystalline layer with higher surface activity promoted the adsorption of a protective oxide layer. These factors decreased the surface roughness, coefficient of friction (COF), and wear rate of N-alloyed high-Mn austenitic steel. This study provided valuable insights into the application of N-alloyed high-Mn austenitic steels under dry sliding friction conditions.

Kinetics of ethane exsolution and dissolution in bitumen

Dissolution and exsolution of gases are common in many engineering applications. Dissolution and exsolution occur across a gas-liquid interface when the equilibrium condition is disturbed. This study presents experimentally measured data on the exsolution and dissolution kinetics of ethane and bitumen (a viscous liquid) system across a temperature range of 80–140 °C and pressure differences of 0.69 and 0.35 MPa. Analytical models were adopted to estimate the exsolution and dissolution coefficients from the measured data for the ethane/bitumen system. The diffusivity values for the exsolution and dissolution processes were estimated to range from (2.65–10.48) × 10−8 m2/s and (0.73–6.18) × 10−9 m2/s, respectively, at a pressure difference of 0.69 MPa, and from (1.61–8.33) × 10−8 m2/s and (0.89–10.78) × 10−9 m2/s, respectively, at a pressure difference of 0.35 MPa. For both pressure differences, the exsolution kinetics were shown to be faster than dissolution in the ethane/bitumen system. This was also confirmed by higher activation energy for the exsolution process calculated using the Arrhenius equation. The results offer valuable insights into the kinetics of gas exsolution and dissolution, with applications in designing and optimizing processes where nonequilibrated gases and liquids are brought into contact.

Processing demands modulate the activities and functional connectivity patterns of the posterior (VWFA-1) and anterior (VWFA-2) VWFA

Previous studies have shown that the visual word form area (VWFA) has structural and intrinsic functional connectivity with both language and attention networks. Nevertheless, it is still unclear how the functional connectivity pattern of the VWFA is regulated by processing demands induced by experimental tasks, and whether processing demands differentially regulate the posterior (VWFA-1) and anterior (VWFA-2) subregions of the VWFA. To address these questions, the present study adopted two tasks varying in processing demands (i.e., verbal and non-verbal tasks), and used generalized psychophysiological interaction (gPPI) and dynamic causal modeling (DCM) analyses to explore the task-dependent functional connectivity patterns of the two subregions of the VWFA. Activation analysis revealed that the VWFA-2 showed higher activation for the verbal task than the non-verbal task, while there were no activation differences in the VWFA-1 after controlling for the stimulus driven effects. Functional and effective connectivity analyses revealed that, for both VWFA-1 and VWFA-2, the verbal task enhanced connections from VWFAs to the ventral language regions (e.g., the left orbital frontal cortex), while the non-verbal task enhanced connections from VWFAs to the dorsal visuospatial regions (e.g., the left intraparietal sulcus). Results of the present study indicate that processing demands induced by tasks modulate both the local activity and functional connectivity patterns of the VWFA, providing new insights for understanding its domain-general function.

Ensiling as a Conservation Technique for Opuntia ficus indica (L.) By-Products: Peel and Pastazzo

Italy is the third largest producer of Opuntia fruits in the world after Mexico and the United States, and 97.72% of these fruits produced by Italy are grown in Sicily. The use of prickly pear fruits or juice leads to a high production of by-products. In this study, ensiling was chosen to preserve prickly pear peels (PPPs) and “pastazzo” (PPS) mixed with 12% wheat bran. PPP silage presented a lower DM than PPS silage (20.03 vs. 41.37%; p < 0.01), as well as aNDFom (25.31 vs. 66.66% DM; p < 0.01), but had the best protein content (12.02 vs. 9.55% DM; p < 0.01). For both by-products, fermentation proceeded rapidly with increasing temperature, with the temperature for PPS (38 °C) being higher than that for the PPP (30 °C). Mesophilic LAB (lactic acid bacteria) were detected at higher levels than thermophilic LAB, and rod counts were higher than cocci counts. The detected organic acids and silage pH indicate an optimal fermentation process for these by-products. PPP silage had a higher polyphenol content than PPS silage (30.24 vs. 24.22 mg GAE/g DM; p < 0.01) and, consequently, also higher antioxidant activity. The results of this study on the mineral composition and macro- and micro-nutrients in silage highlight that these by-products are sources of minerals, with high levels of potassium, calcium, and magnesium.

Reduced Achilles tendon stiffness in aging associates with higher metabolic cost of walking.

The mechanisms responsible for increased metabolic cost of walking in older adults are poorly understood. We recently proposed a theoretical premise by which age-related reductions in Achilles tendon stiffness (kAT) can disrupt the neuromechanics of calf muscle force production and contribute to faster rates of oxygen consumption during walking. The purpose of this study was to objectively evaluate this premise. We quantified kAT at a range of matched relative activations prescribed using electromyographic biofeedback and walking metabolic cost and ankle joint biomechanics in a group of 15 younger (age: 23±4 yrs) and 15 older adults (age: 72±5 yrs). Older adults averaged 44% lower kAT than younger adults at matched triceps surae activations during isokinetic dorsiflexion tasks on a dynamometer (p=0.046). Older adults also walked with a 17% higher net metabolic power (p=0.017) but indistinguishable peak Achilles tendon forces than younger adults. Thus, data implicate altered tendon length-tension relations with age more than differences in the operating region of those length-tension relations between younger and older adults. In addition, we discovered empirical evidence that lesser kAT - likely due to the shorter muscle lengths and thus higher relative activations it imposes - was positively correlated with higher net metabolic power during walking (r=-0.365, p=0.048). These results pave the way for interventions focused on restoring ankle muscle-tendon unit structural stiffness to improve walking energetics in aging.

Associations of sugary beverage intake with type 2 diabetes and the role of physical activity: a prospective cohort study

BackgroundHigher consumption of sugary beverages (SB) has been associated with type 2 diabetes (T2D), but whether these associations are modified by physical activity remains unclear. This study aimed to examine the associations of SB intake, including sugar-sweetened beverages (SSB), artificially sweetened beverages (ASB), and natural juices (NJ) with the risk of incident T2D, and the potential role of physical activity.MethodsWe included 153,862 diabetes-free participants in the UK Biobank who completed both the International Physical Activity Questionnaire at recruitment (2006–2010) and at least one 24-h dietary recall questionnaire in 2009–2012. We assessed the associations of each SB with the risk of incident T2D using Cox proportional hazard models, and explored the interactions between each SB and physical activity.ResultsDuring a median follow-up of 11.8 years, 6631 participants developed incident T2D. Participants consuming more SSB and ASB (comparing > 2 to 0 unit/d) had a higher hazard of T2D (hazard ratio [HR]: 1.17, 95% confidence interval [CI]: 1.05–1.31 for SSB; 1.54, 1.37–1.74 for ASB), while medium intake of NJ showed an inverse association (HR> 0–1 vs. 0 unit/d: 0.87, 95% CI: 0.82–0.92; HR> 1–2 vs. 0 unit/d: 0.88, 95% CI: 0.81–0.97) with incident T2D. No significant interactions between physical activity and SSB/ASB were found (P-interaction=0.204 for SSB, 0.926 for ASB), but the protective association of medium NJ intake with T2D was stronger among participants with higher level of physical activity (P-interaction = 0.043).ConclusionsHigher intake of SSB and ASB was related to higher risks of T2D. Medium NJ intake was associated with a lower risk of T2D, particularly among individuals with higher physical activity level. These findings emphasized the importance of healthy beverage intake and adequate physical activity in diabetes prevention.

Tuning the antioxidant and antibacterial properties of lignin by physicochemical modification during sequential acid precipitation from Kraft black liquor

Turning lignin from black liquor waste into value-added bioactive agents is one of the possible routes for improving the sustainability and profitability of lignocellulosic industry. However, due to chemical and structural variability of lignin, it is necessary to isolate specific lignin fractions from black liquor with the purpose to achieve samples with unique chemical and structural characteristics and therefore, specific biological activities. In this study, poplar lignin fractions isolated from Kraft black liquor by sequential acid precipitation at pH´s 7.5, 5 and 2.5 (denoted as P-7.5, P-5 and P-2.5) were characterized according to their physicochemical, antioxidant and antibacterial properties. In general, lignin fractions displayed a wide elimination of lateral chains (aryl-β ether and C–C) and, therefore a high phenolic content and low molecular weight, as the pH sequential precipitation was decreased from 7.5 to 2.5. Moreover, thermal analysis revealed that the P-7.5 lignin fraction showed higher thermal stability than P-2.5 and P-5. In terms of antioxidant activity, the P-7.5 lignin fraction, with a higher S/G ratio and a less oxidized structure compared to P-5 and P-2.5, exhibited higher antioxidant activity. In addition, lower antibacterial effect was observed for all lignin fractions against Escherichia coli compared to that obtained against Staphylococcus aureus. Among them, the P-2.5 and P-5 fractions, with higher phenolic content and lower molecular weight values than P-7.5, showed a greater antibacterial effect against S. aureus.

Evaluation of Biological Activities of Various Extracts of Glaucium alakirensis, Marrubium bourgaei, and Peucedanum alpinum from Türkiye

Plant species contain many secondary metabolites, and these compounds differ from species to species. These differences in the concentrations of these compounds have many health implications. Today, studies on plants' antioxidant and antibacterial effects are gaining importance. In particular, the adverse effects of some existing antibiotics and the constant development of bacterial resistance are leading to the search for new natural antimicrobial agents. In this study, methanol, ethanol, ethyl acetate, acetone, and chloroform extracts were obtained from the aerial parts of Marrubium bourgaei Boiss and Glaucium alakirensis Aykurt, K.Yıldız & A.Özçandır, and Peucedanum alpinum B.L.Burtt & Davis, species which are naturally distributed in Türkiye. The antioxidant activity of the extracts was determined by the DPPH (2,2 Difenil-1-pikrihidrazil) and ABTS (2,2' azino-bis(3-ethylbenz-thiazoline-6-sulfonic-acid)) methods, the total phenolic content by Folin-Ciocalteu method, the total flavonoid content by aluminium chloride colorimetric method, and the antibacterial activity against ten bacteria by the disc diffusion method. According to the results, methanol, ethanol, and acetone extracts had higher antioxidant activity, total phenolic, and total flavonoid contents than other extracts. However, the total flavonoid content of M. bourgaei was higher in the ethyl acetate extract. When evaluated for their antibacterial activity, ethanol, chloroform, and ethyl acetate in P. alpinum, chloroform in M. bourgaei, and methanol, chloroform, and ethyl acetate in G. alakirensis extracts showed antibacterial activity against more bacteria than others. This is the first study to evaluate and compare the total phenolic and flavonoid content, and antioxidant and antibacterial activities of 5 different extracts of these plants.

Effect of cheese coagulants on American-style natural cheese proteolysis and functional characteristics of process cheese made therefrom

Recombinant bovine chymosin (RBC) is an enzyme routinely used in cheese manufacture. Recombinant camel chymosin (RCC) is a milk coagulant with higher clotting activity and less proteolytic activity for natural cheese manufacture. This study aimed to determine the effect of RCC and RBC on the proteolysis of natural cheese and the functionality of processed cheese (PC). Six American-style natural cheeses were manufactured utilizing two different chymosin treatments and used to produce PC at 1 month of ripening. The natural cheese made using RCC had a significantly (P < 0.05) lower level of primary proteolysis and a lower degree of hydrolysis of αS1-CN and β-CN. The RCC treatment's hot viscosity, hardness, and loss tangent were significantly (P < 0.05) higher than the RBC in the PC. These results demonstrate that RCC results in a reduced level of primary proteolysis in a natural cheese, and when utilized in PC, it increases firmness and decreases meltability.

Applying acoustic telemetry, vessel tracking and fisher knowledge to investigate and manage fisher-shark conflict at Lord Howe Island, Australia

Fisher-shark conflict is occurring at Lord Howe Island, Australia due to high levels of Galapagos shark (Carcharhinus galapagensis) depredation (where sharks consume hooked fish) and bycatch. Depredation causes costly loss of target catch and fishing gear and increased mortality of target species, and sharks can be injured or killed when bycaught. This study applied acoustic telemetry and vessel tracking from 2018 to 2021 to identify; (1) how the movements of 30 tagged sharks and activity of six fishing vessels overlapped, and (2) where key ‘hotspots’ of overlap occurred. Fisher surveys were also conducted to collect information about mitigating shark interactions. Residency index analysis indicated that three sharks tagged at a fish waste dumping site had markedly higher residency. Core home ranges of sharks overlapped with higher fishing activity at four ‘hotspots’. Statistical modelling indicated positive linear effects of fishing activity and bathymetric complexity on shark detections and tagged sharks were present for 13% of the total time that vessels were fishing close to acoustic receivers. Spatio-temporal overlaps between shark movements and fishing activity could potentially have occurred because sharks learned to associate fishing vessels with food (i.e. hooked fish) and because fishers and sharks utilise highly productive shelf edge areas, however more research is needed to investigate these relationships. Fishers reported that rotating fishing areas and reducing time at each location, fishing deeper than 100 m, and using electric reels and lures instead of bait, reduced bycatch and depredation. The integrated approach used here identified practical methods for reducing fisher-shark conflict, improving socio-economic outcomes for fishers and conservation prospects for this unique shark population.

NiIr Nanowire Assembles as an Efficient Electrocatalyst Towards Oxygen Evolution Reaction in Both Acid and Alkaline Media.

Oxygen evolution reaction (OER) is the rate-limiting step in water electrolysis due to its sluggish kinetic, and it is challenging to develop an OER catalyst that could work efficiently in both acid and alkaline environment. Herein, NiIr nanowire assembles (NAs) with unique nanoflower morphology were prepared by a facile hydrothermal method. As a result, the NiIr NAs exhibited superior OER activity in both acid and alkaline media. Specifically, in 0.1 M HClO4, NiIr NAs presented a superior electrocatalytic performance with a low overpotential of merely 242 mV at 10 mA cm-2 and a Tafel slope of only 58.1 mV dec-1, surpassing that of commercial IrO2 and pure Ir NAs. And it achieved a significantly higher mass activity of 148.40 A/g at -1.5 V versus RHE. In 1.0 M KOH, NiIr NAs has an overpotential of 291 mV at 10 mA cm-2 and a Tafel slope of 42.1 mV dec-1. Such remarkable activity makes the NiIr NAs among the best of recently reported representative Ir-based OER electrocatalysts. Density functional theory (DFT) calculations confirmed alloying effect promotes surface bonding of NiIr with oxygen-containing reactants, resulting in excellent catalytic properties.

DKK1+ tumor cells inhibited the infiltration of CCL19+ fibroblasts and plasma cells contributing to worse immunotherapy response in hepatocellular carcinoma

Intra-tumor immune infiltration plays a pivotal role in the interaction with tumor cells in hepatocellular carcinoma (HCC). However, its phenotype and related spatial structure remained elusive. To address these limitations, we conducted a comprehensive study combining spatial data (38,191 spots from eight samples) and single-cell data (56,022 cells from 20 samples). Our analysis revealed two distinct infiltration patterns: immune exclusion and immune activation. Plasma cells emerged as the primary cell type within intra-tumor immune clusters. Notably, we observed the co-location of CCL19+ fibroblasts with plasma cells, which secrete chemokines and promote T-cell activation and leukocyte migration. Conversely, in immune-exclusion samples, this co-location was primarily observed in the adjacent normal area. This co-localization correlated with T cell infiltration and the formation of tertiary lymphoid structures, validated by multiplex immunofluorescence conducted on twenty HCC samples. Both CCL19+ fibroblasts and plasma cells were associated with favorable survival outcomes. In an immunotherapy cohort, HCC patients who responded favorably exhibited higher infiltration of CCL19+ fibroblasts and plasma cells. Additionally, we observed the accumulation of DKK1+ tumor cells within the tumor area in immune-exclusion samples, particularly at the tumor boundary, which inhibited the infiltration of CCL19+ fibroblasts and plasma cells into the tumor area. Furthermore, in immune-exclusion samples, the SPP1 signaling pathway demonstrated the highest activity in communication between tumor and immune clusters, and CCL19-CCR7 played a pivotal role in the self-communication of immune clusters. This study elucidates immune exclusion and immune activation patterns in HCC and identifies relevant factors contributing to immune resistance.

Design, Synthesis, Antibacterial, and Antifungal Evaluation of a New Series of Quinazoline - Thiazole and/or Quinazoline - Triazole Hybrids as Bioactive Heterocycles.

Herein, a one-pot reaction between cyclohexanone, thiourea, and 2,5-dimethoxybenzaldehyde allowed to prepare hexahydroquinazoline-2(1H)-thione4 firstly, which followed by reacting with hydrazine hydrate to produce the corresponding 2-hydrazinylhexahydroquinazoline 6. Interesting analogs of thiazolo[3,2-a]quinazoline 713 where obtained when hexahydroquinazoline-2(1H)-thione 4 reacted with 1,2-dibromoethane, chloroacetyl chloride, bromoacetic acid, bromoacetic acid/4-chlorobenzaldehyde, 2-bromopropionic acid, ethyl bromo cyanoacetate, and/or bromomalononitrile; respectively. While triazolo[4,3-a] quinazoline 14-16 were created when 2-hydrazinylhexahydroquinazoline 6 reacted with triethyl orthoformate, acetic anhydride, and carbon disulfide respectively. Numerous spectroscopy tests, including FT-IR, NMR (1H &13 C), and MS spectrum, proved all the newly produced analogs. Additionally, the new analogs were examined for their antibacterial and antifungal properties against Escherichia coli, Staphylococcus aureus, and Candida albicans. It was discovered that triazolo[4,3-a] quinazoline analogs 14-16 have superior bacterial and fungal activity when compared to the corresponding conventional doses of Streptomycin andGriseofulvin. Towards Candida albicans; compounds 14, 15, and 16 increase activity with 1.14 %, 1.15 %, and 1.21 %, respectively more than griseofulvin.While, for Staphylococcus aureus; compounds 14, 15, and 16 increase activity with 1.5 %, 1.5 %, and 1.7 %, respectively more than streptomycin. Morever, for Escherichia coli; compounds 14, 15, and 16 increase activity with 1.19 %, 1.21 %, and 1.22 %, respectively more than streptomycin. Finally, structure activity relationships show that quinazoline derivatives exhibit higher activity when fused to pyrazole ring 14-16 as compared when fused thiophene ring 7-13.

The influence of tree species on small scale spatial soil properties and microbial activities in a mixed bamboo and broad-leaved forest

Soil enzyme activity and microbial biomass play a critical role in myriad ecological processes. Bamboo and broad-leaved mixed forests have received widespread attention as important forestry models for ecological restoration and sustainable development; however, our understanding the influences of broad-leaved tree species in mixed bamboo forests on soil properties and microbial activity remains unclear. Here we sampled twenty-seven spatially interspersed stands of bamboo-Castanopsis chinensis Hance mixed forest (CCB), bamboo-Alniphyllum fortune (Hemsl.) Makino mixed forest (AFB), and bamboo-Choerospondias axillaris mixed forest (CAB), with different mixing ratios (0–10 %, 10–20 %, 20–40 % canopy proportions) in subtropical China, to examine the effects of tree species and mixed ratio on soil nutrients, microbial biomass, and enzyme activity. We found that the different forests exhibited variations in soil nutrient levels. CAB forests exhibit notably higher mean C, N, and P contents than AFB and CCB, particularly at a 10–20 % mixing ratio where SOC concentration reached 46.50 g/kg. CAB forests demonstrated significantly higher activities of invertase (mean 701.83U/g), urease (8393.44U/g), and catalase (501.73U/g) compared to AFB and CCB forests, with peak enzyme activities observed at a 10–20 % mixing ratio. Soil microbial biomass C and N were notably greater in CAB and CCB forests than in AFB forests. CAB forests also exhibited the highest soil microbial biomass P (mean 48.68 mg/kg), which rose consistently with an increased mixing ratio. Multiple factor analysis revealed that the enzyme activities were significantly correlated with the annual growth of fine roots in the forest and were positively correlated with resident C, total N, total P, C: N, and C: P. Overall, the results provide insights into the importance of tree species and crown size in bamboo and broadleaved tree mixed forest in soil features and the microbial activity while providing management guidance for the selection of mixed tree species for sustainable management of bamboo forest soil microenvironment.