Splenic marginal zone B cells restrict Mycobacterium tuberculosis infection by shaping the cytokine pattern and cell-mediated immunity.

Understanding the role of B cells in tuberculosis (TB) is crucial for developing new TB vaccines. However, the changes in B cell immune landscapes during TB and their functional implications remain incompletely explored. Using high-dimensional flow cytometry to map the immune landscape in response to Mycobacterium tuberculosis (Mtb) infection, our results show an accumulation of marginal zone B (MZB) cells and other unconventional B cell subsets in the lungs and spleen, shaping an unconventional B cell landscape. These MZB cells exhibit activated and memory-like phenotypes, distinguishing their functional profiles from those of conventional B cells. Notably, functional studies show that MZB cells produce multiple cytokines and contribute to systemic protection against TB by shaping cytokine patterns and cell-mediated immunity. These changes in the immune landscape are reversible upon successful TB chemotherapy. Our study suggests that, beyond antibody production, targeting the regulatory function of B cells may be a valuable strategy for TB vaccine development.

Trans-2-nonadecyl-4-(hydroxymethyl)-1,3-dioxolane (TNHD) purified from freshwater clams markedly alleviates dimethylnitrosamine-induced hepatic fibrosis.

Liver fibrosis occurs due to injury or inflammation, which results in the excessive production of collagen and the formation of fibrotic scar tissue that impairs liver function. Despite the limited treatment options available, freshwater clams may hold promise in the treatment of liver fibrosis. In this study, we demonstrated the effects of ethanol extract of freshwater clam (FCE), ethyl acetate extract of FCE (EA-FCE), and trans-2-nonadecyl-4-(hydroxymethyl)-1,3-dioxolane (TNHD) on liver fibrosis induced by dimethylnitrosamine (DMN). Administration of FCE and TNHD alleviated liver injury, including tissue damage, necrosis, inflammation scores, fibrosis scores, serum enzymes, and triglyceride levels. Furthermore, we analyzed the expression of fibrosis-related proteins, such as α-smooth muscle actin (α-SMA) and transforming growth factor (TGF-ß), as well as the hydroxyproline content, which decreased after treatment with FCE and TNHD. Animal experiments revealed that FCE and TNHD can reduce liver fibrosis by inhibiting cytokines that activate stellate cells and decreasing extracellular matrix (ECM) secretion. Cell experiments have shown that TNHD inhibits the MAPK/Smad signaling pathway and TGF-ß1 activation, resulting in a reduction in the expression of fibrosis-related proteins. Therefore, freshwater clam extracts, particularly TNHD, may have potential therapeutic and preventive effects for the amelioration of liver fibrosis.

Wild mouse gut microbiota limits initial tuberculosis infection in BALB/c mice.

Mouse models are critical tools in tuberculosis (TB) research. Recent studies have demonstrated that the wild mouse gut microbiota promotes host fitness and improves disease resistance. Here we examine whether the wild mouse gut microbiota alters the immunopathology of TB in BALB/c mice. Conventional BALB/c mice (LabC) and mice born to germ-free BALB/c mothers reconstituted with the wild mouse gut microbiota (WildR) were used in our studies. WildR mice controlled initial TB infection better than LabC mice. The microbial gut communities of LabC mice and WildR mice had similar richness but significantly different composition prior to infection. TB reduced the gut community richness in both cohorts while differences in community composition remained indicating a general TB-induced dysbiosis. The wild mouse gut microbiota did not alter the typical lung histopathology of TB in the BALB/c model that includes unstructured immune cell infiltrates with infected foamy macrophages invading alveolar spaces. Animals of both cohorts mounted robust T cell responses in lungs and spleen with lower absolute counts of CD4 and CD8 T cells in lungs of WildR mice during acute infection, corresponding with observed differences in pathogen load. In summary, LabC mice and WildR mice showed largely overlapping TB immunopathology and pathogen kinetics, with WildR mice controlling early acute infection better than LabC mice.

Rapid identification and detection of aristolochic acids in the herbal extracts by Raman spectroscopy.

Herbs containing aristolochic acids (AAs) have already been proven to be highly carcinogenic and nephrotoxic. In this study, a novel surface-enhanced Raman scattering (SERS) identification method was developed. Ag-APS nanoparticles with a particle size of 3.53 ± 0.92 nm were produced by combining silver nitrate and 3-aminopropylsilatrane. The reaction between the carboxylic acid group of aristolochic acid I (AAI) and amine group of Ag-APS NPs was used to form amide bonds, and thus, concentrate AAI, rendering it easy to detect via SERS and amplified to obtain the best SERS enhancement effect. Detection limit was calculated to be approximately 40 nM. Using the SERS method, AAI was successfully detected in the samples of four Chinese herbal medicines containing AAI. Therefore, this method has a high potential to be applied in the future development of AAI analysis and rapid qualitative and quantitative analysis of AAI in dietary supplements and edible herbs.

Quantum dot assisted precise and sensitive fluorescence-based formaldehyde detection in food samples.

Formaldehyde has an extremely reactive carbonyl group, commonly used as an antibacterial agent to sterilize and prevent food to spoil. This article describes an efficient and rapid detection method of formaldehyde from an aqueous solution by synthesizing 3-Aminopropyltriethoxysilane (APTES) quantum dots (Nano A) which react with formaldehyde to generate a Schiff base reaction. The photoinduced electron transfer produced by the quantum dots themselves results in fluorescence quenching to detect formaldehyde. The detection limit can reach 10-9 M, and it can further be used to detect formaldehyde content in foods, such as baby vegetables, mushrooms, and vermicelli among other daily foods.

Detecting the release of plastic particles in packaged drinking water under simulated light irradiation using surface-enhanced Raman spectroscopy.

Plastic cups and bottles used for mineral water packaging may release plastic particles during continuous exposure to heat, light, or unfavorable chemical environments during transportation and storage. Surface-enhanced Raman spectroscopy (SERS) can be used to detect and analyze these plastic particles in a highly sensitive and quantitative manner. In this study, we used copper oxide/silver nanoparticles (CuO/Ag NPs) as the SERS substrate to monitor the release of plastic particles in packaged mineral water samples under irradiation as a function of exposure time. The lower detection limit for plastic particles using this CuO/Ag NP SERS system was 1.6 ng/mL. Our results showed that both plastic cups and bottles released particles under irradiation, however, the plastic cup samples degraded much more readily, with the particle concentration increasing considerably from 5.37 ± 0.11 ng/mL to 3751 ± 0.19 ng/ml over the total exposure time period of 240 min. In this study, we have demonstrated that SERS can provide a highly sensitive, rapid, and economical method for detecting plastic particle contamination caused by degradation of the plastic materials used in mineral water packaging.

Engineered mesoporous biochar derived from rice husk for efficient removal of malachite green from wastewaters.

Extremely soluble Malachite green (MG) acts as potential carcinogen for aquatic life in polluted aqueous environments. Current study aims to modify rice husk derived biochar to improve its removal efficiency for MG from MG-containing wastewaters. The hydrothermal alkali activation was effective for preparing modified biochar (RHMB) from native biochar (RHB) derived from rice husk. After modification, surface area and pore volume of RHMB was determined respectively 434.62 m2g-1 and 287.28 cm3g-1, significantly improved from native RHB values 21.764 m2g-1 and 65.53 cm3g-1. Pseudo second order kinetic model fitted well. RHMB exhibits an equilibrium adsorption capacity of 373.02 mg g-1. RHMB showed an excellent MG removal ability and was not susceptible to ion interference even at highly saline environments. It has exhibited 96.96 ± 1.17% removal efficiency of MG and is expected to be used as potential adsorbent for MG remediation from aquaculture wastewater and other MG containing industrial wastewaters.

Correlation of Neutralizing Antibodies (NAbs) between Sows and Piglets and Evaluation of Protectability Associated with Maternally Derived NAbs in Pigs against Circulating Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) under Field Conditions.

Porcine reproductive and respiratory syndrome (PRRS), which is caused by a highly transmissible pathogen called porcine reproductive and respiratory syndrome virus (PRRSV), has caused severe problems, including reproductive disorders in sows and respiratory symptoms in nursery pigs worldwide, since the early 1990s. However, currently available PRRSV vaccines do not supply complete immunity to confront the viral infection. Elicitation of PRRSV-specific neutralizing antibodies (NAbs) during the preinfectious period has been deemed to be a feasible strategy to modulate this virus, especially in farms where nursery pigs are seized with PRRSVs. A total of 180 piglets in a farrow-to-finish farm that had a natural outbreak of PRRS were distributed into three groups based on the different PRRSV NAbs levels in their dams. In the present study, piglets that received superior maternal-transferred NAbs showed delayed and relatively slight viral loads in serum and, on the whole, higher survival rates against wild PRRSV infections. A positive correlation of maternal NAbs between sows and their piglets was identified; moreover, high NAbs titers in piglets can last for at least 4 weeks. These results provide updated information to develop an appropriate immune strategy for breeding and for future PRRSV control under field conditions.

Hybrid nano-textured nanogenerator and self-powered sensor for on-skin triggered biomechanical motions.

Researchers have made a lot of effort for the lightweight and high flexibility of wearable electronic devices, which also requires the associated energy harvesting equipment to have ultra-thin thickness and high stretchability. Therefore, a piezoelectric-triboelectric hybrid self-powered sensor (PTHS) has been proposed which can be used as the second layer of the human body. This elastic PTHS can even work on a person's fingers without disturbing the body's movements. The open circuit voltage and short circuit current of devices with a projected area of 30 mm × 25 mm can reach 1.2 V and 30 nA, respectively. Two piezoelectrically-triboelectrically sensors with machine learning optimized identification strategies were experimentally proven as the potential applications of the PTHS. The PTHS's ultra-thin thickness, high stretchability and superior geometry control features are promising in electronic skin, artificial muscle and soft robotics. The novelty of this work is that a smart mask integrated with PTHS can generate a signal of the hybrid sensor for the biomechanical motion classifier. After suitable training, an overall accuracy of 87.9% using long short-term memory can be achieved.

CCM111 prevents hepatic fibrosis via cooperative inhibition of TGF-ß, Wnt and STAT3 signaling pathways.

CCM111 is an aqueous extract of Antrodia cinnamomea (AC) that has exhibited anti-liver fibrosis functions. However, the detailed mechanisms of AC action against liver fibrosis have not been elucidated yet. The present research showed that CCM111 significantly lowered the levels of the hepatic enzyme markers glutamate oxaloacetate transaminase (GOT) and glutamic pyruvic transaminase (GPT), prevented liver damage and collagen deposition, and downregulated TGF-ß/Smad signaling in a dose-dependent manner compared with CCl4 treatment alone. CCM111 markedly inhibited TGF-ß, Wnt and STAT3 signaling pathway-regulated downstream genes in the liver by next-generation sequencing. The antifibrotic mechanisms of CCM111 were further demonstrated in HSC-T6 cells. Our data demonstrated for the first time that CCM111 can protect against CCl4-induced liver fibrosis by the cooperative inhibition of TGF-ß-, Wnt- and STAT3-dependent proinflammatory and profibrotic mediators, suggesting that CCM111 might be a candidate for preventing and treating chronic fibrotic liver diseases.

Near-Field Electrospun Piezoelectric Fibers as Sound-Sensing Elements.

A novel integration of three-dimensional (3D) architectures of near-field electrospun polyvinylidene fluoride (PVDF) nano-micro fibers (NMFs) is applied to an intelligent self-powered sound-sensing element (ISSE). Using 3D architecture with greatly enhanced piezoelectric output, the sound wave energy can be harvested under a sound pressure of 120+ dB SPL of electrical signal about 0.25 V. Furthermore, the simple throat vibrations such as hum, cough and swallow with different intensity or frequency can be distinguishably detected. Finally, the developed ultrathin ISSE of near-field electrospun piezoelectric fibers has the advantage of direct-write fabrication on highly flexible substrates and low cost. The proposed technique demonstrates the advancement of existing electrospinning technologies in new practical applications of sensing purposes such as voice control, wearable electronics, implantable human wireless technology.

Self-Powered Pressure Sensor with fully encapsulated 3D printed wavy substrate and highly-aligned piezoelectric fibers array.

Near-field electrospinning (NFES) is capable of precisely deposit one-dimensional (1D) or two-dimensional (2D) highly aligned micro/nano fibers (NMFs) by electrically discharged a polymer solution. In this paper, a new integration of three-dimensional (3D) architectures of NFES electrospun polyvinylidene fluoride (PVDF) NMFs with the 3D printed topologically tailored substrate are demonstrated in a direct-write and in-situ poled manner, called wavy- substrate self-powered sensors (WSS). The fabrication steps are composed of the additive manufacture of 3D printed flexible and sinusoidal wavy substrate, metallization and NFES electrospun fibers in the 3D topology. This 3D architecture is capable of greatly enhancing the piezoelectric output. Finally, the proposed piezoelectrically integrated 3D architecture is applied to the self-powered sensors such as foot pressure measurement, human motion monitoring and finger-induced power generation. The proposed technique demonstrates the advancement of existing electrospinning technologies in constructing 3D structures and several promising applications for biomedical and wearable electronics.

Protective effect of theaflavin-enriched black tea extracts against dimethylnitrosamine-induced liver fibrosis in rats.

Liver cirrhosis is responsible for hepatic fibrosis resulting in high mortality and is also a risk factor for developing hepatocellular carcinoma (HCC), which is the fifth most common cancer in men and the seventh in women globally. Several studies have found effective anti-cancer activities of theaflavins, the major black tea polyphenols. The objective of this study was to investigate the protective effects of theaflavin-enriched black tea extracts (TF-BTE) on hepatic fibrosis induced by dimethylnitrosamine (DMN) administration in Sprague-Dawley (SD) rats. Treatment of SD rats with DMN (10 mg per kg bw) for 4 weeks produced inflammation and remarkable liver fibrosis assessed by serum biochemistry and histopathological examination. Fibrotic status and the activation of hepatic stellate cells were improved by oral administration of 40% theaflavins in black tea extracts (40% TF-BTE) as evidenced by histopathological examination. Oral administration of 40% TF-BTE at a low dose of 50 mg per kg bw per day and a high dose of 100 mg per kg bw per day attenuated the DMN-induced elevation of serum GOT (glutamate oxaloacetate transaminase) and GPT (glutamic pyruvic transaminase) levels and reduced necrosis, bile duct proliferation, and inflammation. Western blot analyses revealed that TF-BTE inhibited the expression of liver alpha-smooth muscle actin (α-SMA) and transforming growth factor-ß1 (TGF-ß1) protein. The histochemical examination showed the inhibitory effect of TF-BTE on the p-Smad3 expression. Overall, these data demonstrated that TF-BTE exhibited hepatoprotective effects on experimental fibrosis, potentially by inhibiting the TGF-ß1/Smad signaling.

Type I IFNs and IL-18 regulate the antiviral response of primary human γδ T cells against dendritic cells infected with Dengue virus.

Little is known about the cellular mechanisms of innate immunity against dengue virus (DV) infection. Specifically, the γδ T cell response to DV has not been characterized in detail. In this article, we demonstrate that markers of activation, proliferation, and degranulation are upregulated on γδ T cells in PBMC isolated from individuals with acute dengue fever. Primary γδ T cells responded rapidly in vitro to autologous DV-infected dendritic cells by secreting IFN-γ and upregulating CD107a. The anti-DV IFN-γ response is regulated by type I IFN and IL-18 in a TCR-independent manner, and IFN-γ secreting γδ T cells predominantly expressed IL-18Rα. Antagonizing the ATP-dependent P2X7 receptor pathway of inflammasome activation significantly inhibited the anti-DV IFN-γ response of γδ T cells. Overnight priming with IL-18 produced effector γδ T cells with significantly increased ability to lyse autologous DV-infected dendritic cells. Monocytes were identified as accessory cells that augmented the anti-DV IFN-γ response of γδ T cells. Lack of monocytes in culture is associated with lower IL-18 levels in culture supernatant and diminished production of IFN-γ by γδ T cells, whereas addition of exogenous IL-18 restored the IFN-γ response of γδ T cells in monocyte-depleted cocultures with DV-infected DC. Our results indicate that primary γδ T cells contribute to the immune response during DV infection by providing an early source of IFN-γ, as well as by killing DV-infected cells, and suggest that monocytes participate as accessory cells that sense DV infection and amplify the cellular immune response against this virus in an IL-18-dependent manner.

The combination of type I IFN, TNF-α, and cell surface receptor engagement with dendritic cells enables NK cells to overcome immune evasion by dengue virus.

Clinical studies have suggested the importance of the NK cell response against dengue virus (DenV), an arboviral infection that afflicts >50 million individuals each year. However, a comprehensive understanding of the NK cell response against dengue-infected cells is lacking. To characterize cell-contact mechanisms and soluble factors that contribute to the antidengue response, primary human NK cells were cocultured with autologous DenV-infected monocyte-derived dendritic cells (DC). NK cells responded by cytokine production and the lysis of target cells. Notably, in the absence of significant monokine production by DenV-infected DC, it was the combination of type I IFNs and TNF-α produced by DenV-infected DC that was important for stimulating the IFN-γ and cytotoxic responses of NK cells. Cell-bound factors enhanced NK cell IFN-γ production. In particular, reduced HLA class I expression was observed on DenV-infected DC, and IFN-γ production was enhanced in licensed/educated NK cell subsets. NK-DC cell contact was also identified as a requirement for a cytotoxic response, and there was evidence for both perforin/granzyme as well as Fas/Fas ligand-dependent pathways of killing by NK cells. In summary, our results have uncovered a previously unappreciated role for the combined effect of type I IFNs, TNF-α, and cell surface receptor-ligand interactions in triggering the antidengue response of primary human NK cells.

Protective effects of garcinol on dimethylnitrosamine-induced liver fibrosis in rats.

Garcinol, a polyisoprenylated benzophenone derivative, mainly isolated from Garcinia indica fruit rind, has been suggested to exhibit many biological benefits including antioxidative, anti-inflammatory, and anti-tumor activities. The aim of this study is to evaluate the protective effects of garcinol on dimethylnitrosamine (DMN)-induced liver fibrosis in rats. The administration of DMN for six consecutive weeks resulted in the decrease of body weights, the elevation of serum aminotransferases, as well as histological lesions in livers. However, oral administration of garcinol remarkably inhibited the elevation of aspartate transaminase (AST) and relieved liver damage induced by DMN. Furthermore, our results revealed that garcinol not only effectively reduced the accumulation of extracellular matrix (ECM) components but also inhibited the expression of α-smooth muscle actin (α-SMA) in livers. The expression of transforming growth factor-ß1 (TGF-ß1) and the phosphorylation of Smad 2 and Smad 3 were also suppressed by garcinol supplementation. In conclusion, our current study suggested that garcinol exerted hepatoprotective and anti-fibrotic effects against DMN-induced liver injury in rats.

Inotilone suppresses phorbol ester-induced inflammation and tumor promotion in mouse skin.

SCOPE: Chemoprevention is one of the most feasible approaches to reduce the risk of cancer. Over the past decades, scientists have realized that chronic inflammation is a critical component of cancer development. Inotilone, existing in Inonotus mushroom has been reported to exhibit anti-inflammatory properties in vitro. Hence, we investigated the effects of inotilone on 12-O-tetradecanoylphorbol-13-acetate (TPA)-mediated acute inflammation and tumor promotion in mouse skin and the underlying molecular mechanisms. METHODS AND RESULTS: Inotilone was topically applied to mouse skin 30 min prior to TPA treatment. The results have shown that inotilone inhibited the production of inflammatory mediators by attenuating the activation of nuclear factor-κB (NF-κB) and the expression of CCAAT/enhancer binding protein ß (C/EBPß). Furthermore, the ability of inotilone to prevent tumorigenesis at promotion stage was evaluated using a classical two-stage mouse skin carcinogenesis model. After initiation of 7,12-dimethylbenz[a]anthracene (DMBA), applying inotilone topically before each TPA treatment was found to reduce the tumor incidence and tumor multiplicity of papillomas. CONCLUSION: Based on the results, we concluded that inotilone has potential to be developed into an effective chemopreventive agent for the treatment of a variety of inflammatory diseases, especially the prevention and treatment of epithelial skin cancer.

Lagrangian-Eulerian micromotion and wave heating in nonlinear self-excited dust-acoustic waves.

We investigate particle-wave microdynamics in the large amplitude self-excited dust acoustic wave at the discrete level through direct visualization. The wave field induces dust oscillations which in turn sustain wave propagation. In the regular wave with increasing wave amplitude, dust-wave interaction with uncertain temporary crest trapping and dust-dust interaction lead to the transition from cyclic to disordered dust motion associated with the liquid to the gas transition, and anisotropic non-Gaussian heating. In the irregular wave, particle trough-trapping is also observed, and the heating is nearly Gaussian and less anisotropic.