Search

Lead (Pb) is a highly toxic metal with no physiological function in humans, accumulates in the body through food intake, and causes gut microbiome disorders and other hazards. In the present study, we examined the efficacy of a combination of chondroitin sulfate and Lactiplantibacillus plantarum CCFM8661 (CCFM8661 + CS) on tissue Pb accumulation and pathological damage to the liver and kidneys, gut microbiota, and fecal metabolites in Pb-exposed mice. Oral administration of CCFM8661 + CS to Pb-exposed mice reduced Pb accumulation in the liver, kidney, and bone tissues (from 3.70, 14.11 and 121.20 mg g -1 wet tissue to 2.26, 8.72 and 65.57 mg g -1 wet tissue, respectively) and increased total antioxidant capacity, superoxide dismutase, and glutathione in the liver and kidneys. Additionally, gut microbiome analysis showed that CCFM8661 + CS intervention attenuated Pb-induced perturbation in gut microbiota, altering the abundance of bacteria such as Faecalibaculum , Ruminococcaceae UCG 014 , Anaerostipes , and Enterorhabdus . Untargeted metabolomics analyses showed that CCFM8661 + CS significantly increased cinnamoylglycine, hippuric acid, and equol (to 31.24, 28.77 and 20.13 times the baseline, respectively) and decreased guanine and 4-coumaric acid (0.30 and 0.09 times the baseline, respectively) in the feces, affecting pathways such as purine and amino acid metabolism. Further analyses showed that promoting Pb excretion and restoring the Pb-impaired gut microbiome and its metabolism may be important contributors to CCFM8661 + CS alleviation of Pb toxicity.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by widespread organ and tissue involvement, with lupus nephritis (LN) being one of its most severe complications. Dietary flavonoids, as for their anti-inflammatory and antioxidant properties, have shown therapeutic potential under various inflammatory conditions. Apigenin (AP) is one of the most studied phenolics and is found in many fruits, vegetables and herbs. This study aimed to investigate the therapeutic effects and underlying mechanisms of apigenin on LN. We evaluated the effects of apigenin on MRL/lpr mice, a well-established model for spontaneous LN. Apigenin treatment improved peripheral blood profiles, reduced serum inflammatory cytokines (IL-6, IFN-γ, IL-17, TGF-β), lowered levels of autoantibodies (ANA, anti-dsDNA) and alleviated renal damage caused by autoantibodies and inflammatory cell infiltration. The results of immunohistochemistry and transcriptome analysis showed that AP could inhibit the infiltration of CD8 + cells in renal tissues. Single-cell sequencing public data from LN patients identified cytotoxic T lymphocytes (CTLs) as the primary CD8 + T cell subtype in the kidneys, with their differentiation regulated by STAT3. In this study, cell experiments demonstrated that AP can induce apoptosis in CD8 + T cells and reduce their recruitment of macrophages by inhibiting the STAT3/IL-17 signaling pathway. These findings highlight that a diet rich in dietary flavonoids, particularly apigenin, can offer therapeutic benefits for patients with SLE.

The use of artificial enzymes and light energy in photocatalytic therapy, a developing drug-free therapeutic approach, can treat malignant tumors in vivo . However, the relatively deficient oxygen concentration in the tumor microenvironment (TME) restrains their further tumor treatment capability. Herein, a novel nanoplatform with Cu 7 S 4 @Au nanocatalyst coated by MnO 2 was successfully designed. After 1064 nm light irradiation, the designed nanocatalyst can promote the separation of light generated electron-hole pairs, resulting in ROS generation and tumor cell apoptosis. The MnO 2 shelled nanoplatform can function as a TME-responsive oxygen self-supplied producer to improve photocatalyst treatment and GSH depletion. In summary, the designed novel nanoplatform shows efficient inhibition of tumor growth via GSH depletion and synergistic photocatalytic therapy, which is of great significance for improving the clinical tumor treatment effect.

The linking chemistry between molecular catalysts and substrates is a crucial challenge for enhancing electrocatalytic performance. Herein, we elucidate the influence of various immobilization methods of amino-substituted Ni phthalocyanine catalysts on their electrocatalytic CO 2 reduction reaction (eCO 2 RR) activity. A graphite-conjugated Ni phthalocyanine, Ni(NH 2 ) 8 Pc-GC, demonstrates remarkable electrocatalytic performance both in H-type and flow cells. In situ infrared spectroscopy and theoretical calculations reveal that the graphite conjugation, through strong electronic coupling, increases the electron density of the active site, reduces the adsorption energy barrier of *COOH, and enhances the catalytic performance. As the cathode catalyst, Ni(NH 2 ) 8 Pc-GC also displays remarkable charge-discharge cycle stability of over 50 hours in a Zn-CO 2 battery. These findings underscore the significance of immobilization methods and highlight the potential for further advancements in eCO 2 RR., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Probiotics can alleviate alcoholic liver disease. However, whether inactive counterparts can produce similar outcomes requires further investigation. We investigated the effects of viable (V) and dead (D) Lactobacillus paracasei CCFM1120 on alcohol-induced ALD mice. The results showed that CCFM1120V and D ameliorated the disease symptoms and intestinal injury. Specifically, these interventions strengthened the intestinal barrier, as evidenced by the increased expression of ZO-1 (zonula occludens 1), occludin, and claudin-1 in the colon and the restored ileal microstructure, including the villi and crypts. In addition, they enhanced the antioxidant capacity of the liver by reducing the production of malondialdehyde and increasing the levels of glutathione and superoxide dismutase. The activation of Nrf2 and HO-1 may be responsible for recovering the antioxidant capacity. Interventions can decrease mouse TNF-α, IL-6 and IL-1β content in serum, probably through the TLR4/MyD88/NF-κB pathway. Furthermore, they possess the ability to restore the quantities of bacteria responsible for producing butyric acid, such as Lactobacillus , Blautia , Bifidobacterium , Ruminococcaceae , Faecalibaculum and Lachnospiraceae . Taken together, CCFM1120V and D apparently can modify the composition of the gut microbiota, foster the gastrointestinal equilibrium, fortify the intestinal barrier, augment the antioxidant capacity of the liver, and effectively shield it from ethanol-induced injury.

Liver injury is a life-threatening condition, and the hepatoprotective potential of cyanidin-3-glucoside (C3G) has been previously demonstrated. However, due to the low bioavailability, it has been doubtful that relatively low concentrations of intact C3G in vivo could account for these bioactivities. In this study, the hepatoprotective effects of intragastric and intravenous administration of C3G were investigated in a CCl 4 induced liver injury model. Intragastric C3G administration was more effective than intravenous C3G injection in reducing serum damage biomarkers, oxidative stress, and inflammatory responses, indicating that absorption of C3G into the bloodstream does not fully account for its observed benefits in vivo . Furthermore, intragastric C3G administration modulated the gut microbiota structure and increased the contents of five metabolites in the feces and serum with high inter-individual variation, indicating the key role of the interaction between C3G and the gut microbiota. At equivalent doses, the metabolites cyanidin and protocatechuic acid exhibited greater efficacy than C3G in reducing apoptosis and ROS production by activating the Nrf2 pathway in an AAPH-induced oxidative stress model. To achieve the desired health effects via C3G-rich food intake, more attention should be paid to microbially derived catabolites. Screening of specific metabolite-producing strains will help overcome individual differences and enhance the health-promoting effects of C3G.

Gastrointestinal inflammation and intestinal barrier function have important effects on human health. Alcohol, an important foodborne hazard factor, damages the intestinal barrier, increasing the risk of disease. Lactobacillus reuteri strains have been reported to reduce gastrointestinal inflammation and strengthen the intestinal barrier. In this study, we selected three anti-inflammatory L. reuteri strains to evaluate their role in the protection of the intestinal barrier and their immunomodulatory activity in a mouse model of gradient alcohol intake. Among the three strains tested (FSCDJY33M3, FGSZY33L6, and FCQHCL8L6), L. reuteri FSCDJY33M3 was found to protect the intestinal barrier most effectively, possibly due to its ability to reduce the expression of interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha (TNF-α) and increase the expression of tight junction proteins (occludin, claudin-3). Genomic analysis suggested that the protective effects of L. reuteri FSCDJY33M3 may be related to functional genes and glycoside hydrolases associated with energy production and conversion, amino acid transport and metabolism, carbohydrate transport and metabolism, and DNA replication, recombination, and repair. These genes include COG2856 , COG1804 , COG2071 , and COG1061 , which encode adenine deaminase, acyl-CoA transferases, glutamine amidotransferase, RNA helicase, and glycoside hydrolases, including GH13_20, GH53, and GH70. Our results identified functional genes that may be related to protection against alcohol-induced intestinal barrier damage, which might be useful for screening lactic acid bacterial strains that can protect the intestinal barrier.

Inulins, galacto-oligosaccharides (GOS) and polyphenols are considered to stimulate the growth of Akkermansia muciniphila ( A. muciniphila ) in the gut. We performed a meta-analysis of six microbiome studies (821 stool samples from 451 participants) to assess the effects of inulin, GOS, and polyphenols on the abundance of A. muciniphila in the gut. The intervention of GOS increased the relative abundance of A. muciniphila in healthy participants. Additionally, metabolic pathways associated with carbohydrate metabolism and short-chain fatty acid release were enriched following the GOS intervention. Furthermore, after the GOS intervention, the coexisting microbial communities of A. muciniphila , such as Eubacterium hallii and Bacteroides , exhibited an enhanced correlation with A. muciniphila . In conclusion, our findings suggest that GOS may promote the growth of A. muciniphila in the gut by modulating the gut microbiota composition.

Antibiotic-associated diarrhea (AAD) is a self-limiting condition that can occur during antibiotic therapy. Our previous studies have found that a combination of Bacteroides uniformis and Bifidobacterium adolescentis can effectively alleviate AAD. However, the use of B. uniformis is still strictly limited. Therefore, this study attempted to use yeast β-glucan to enrich the abundance of B. uniformis in the intestine and supplement Bifidobacterium adolescentis to exert a synergistic effect. The lincomycin hydrochloride-induced AAD model was administered yeast β-glucan or a mixture of B. adolescentis CCFM1285 by gavage for one week. Subsequently, changes in the colonic histopathological structure, inflammatory factors, intestinal epithelial permeability and integrity, metabolites, and gut microbiota diversity were assessed. We found that yeast β-glucan, alone or in combination with B. adolescentis CCFM1285, can help attenuate systemic inflammation, increase the rate of tissue structural recovery, regulate metabolism, and restore the gut microbiota. Specifically, the combination of yeast β-glucan and B. adolescentis CCFM1285 was more effective in decreasing interleukin-6 levels, improving pathological changes in the colon, and upregulating occludin expression. Therefore, our study showed that the combination of yeast β-glucan and B. adolescentis CCFM1285 is an efficacious treatment for AAD.

Bacteroides is a common intestinal bacterium closely associated with host colitis. However, relevant studies have been focused on the genus level, which could not identify the major Bacteroides species associated with intestinal disease. Thus, we have evaluated the Bacteroides species structure in healthy people and mouse intestinal tracts and explored the change in major Bacteroides species during colitis development. The results demonstrated that B. uniformis with a high abundance in the intestinal tract of healthy people and mice may be a core species that contributes to colitis remission. The results of animal experiments reported that B. uniformis FNMHLBE1K1 (1K1) could alleviate the severity of colitis and enhance the expression of the tight junction protein occludin by regulating gut microbiota. Notably, the protective roles of 1K1 may be attributed to some specific genes. This study revealed that B. uniformis is a key microbe influencing the occurrence and development of colitis and it provides a scientific basis for screening the next generation of probiotics.

Valley is used as a new degree of freedom for information encoding and storage. In this work, the valley and topological properties of the VSiGeP 4 monolayer were studied by adjusting the U value based on first-principles calculations. The VSiGeP 4 monolayer remains in a ferromagnetic ground state regardless of the change in the U value. The magnetic anisotropy of the VSiGeP 4 monolayer is initially in-plane, and then turns out-of-plane with the increase in the U value. Moreover, a topological phase transition is observed in the present VSiGeP 4 monolayer with the increase in U value from 0 to 3 eV, i.e. , the VSiGeP 4 monolayer behaves as a bipolar magnetic semiconductor, a ferrovalley semiconductor, a half-valley metal characteristic, and a quantum anomalous Hall state. The mechanism of the topological phase transition behavior of the VSiGeP 4 monolayer was analyzed. It was found that the variation in U values would change the strength of the electronic correlation effect, resulting in the valley and topological properties. In addition, carrier doping was studied to design a valleytronic device using this VSiGeP 4 monolayer. By doping 0.05 electrons per f.u., the VSiGeP 4 monolayer with a U value of 3 eV exhibits 100% spin polarization. This study indicates that the VSiGeP 4 monolayer has potential applications in spintronic, valleytronic, and topological electronic nanodevices.

The porous structure of composite nanofibers plays a key role in improving their electrochemical performance. However, the dynamic evolution of pore structures and their action during ion intercalation/extraction processes for negative electrodes are not clear. Herein, porous carbon composite nanofibers (Fe@Fe 2 O 3 /PCNFs) were prepared as negative electrode materials for potassium-ion batteries. Electrochemical test findings revealed that the composites had good electrochemical characteristics, and the porous structure endowed composite electrodes with pseudo-capacitive behaviors. After 1500 discharge/charge cycles at a current density of 1000 mA g -1 , the specific capacity of the potassium-ion batteries was 144.8 mAh g -1 . We innovatively used synchrotron small-angle X-ray scattering (SAXS) technique to systematically investigate the kinetic process of potassium formation in composites and showed that the kinetic process of potassium reaction in composites can be divided into four stages, and the pores with smaller average diameter distribution are more sensitive to changes in the reaction process. This work paves a new way to study the deposition kinetics of potassium in porous materials, which facilitates the design of porous structures and realizes the development of alkali metal ion-anode materials with high energies.

Fructooligosaccharides (FOS) and inulin are beneficial for human health. However, their benefits differ in individuals who consume prebiotics. Several factors contribute to this variation, including host genetics and differences in the gut microbiota. Bifidobacterium and Bacteroides are strong carbohydrate-utilizing bacteria in the gut, and the level of the Bacteroides / Bifidobacterium (Ba/Bi) ratio in the gut is closely related to the body's ability to utilize prebiotics. However, how to select the type of prebiotics more beneficial for populations with specific Ba/Bi backgrounds and the underlying regulatory mechanisms remain unclear. Here, we explored the dynamics of the gut microbiota and metabolic functions during the in vitro fermentation of FOS and inulin in two different groups: Bacteroides / Bifidobacterium high (H) and Bacteroides / Bifidobacterium low (L). This study revealed that the baseline Ba/Bi ratio had a greater impact on the gut microbiota compared to prebiotic species. Noticeable differences were observed between the two groups after prebiotic intervention, with the H group being more likely to benefit from the prebiotic intervention. Compared to the L group, the H group exhibited significantly higher microbial α-diversity; the co-abundance response group 1 (CARG1) members Ruminococcus gnavus and Blautia involved in the synthesis of propionic and butyric acids increased significantly, the abundance of pathogenic bacteria such as Escherichia Shigella decreased significantly, and the ability to degrade carbohydrates and synthesize fatty acids was greater. Regression modeling showed that the key microbiota could predict the short-chain fatty acid (SCFA) levels, with FOS associated with the ecological roles of CARG2 and CARG7 and inulin associated with CARG4, which provides the basis for the use of prebiotics in nutritional applications and the stratification of populations based on pertinent microbiota profiles to explain the incongruent health effects in human intervention studies.

The wide application of immune checkpoint blockade (ICB) therapy is impeded by the development of ICB-induced colitis, a condition intricately linked to alterations in the gut microbiota. In our previous study, Ligilactobacillus salivarius CCFM 1266 and Bacteroides fragilis HCK-B3 exhibited anti-inflammatory properties. In this research, treatment with both L. salivarius CCFM 1266 and B. fragilis HCK-B3 significantly ameliorated body weight loss and colonic inflammation in murine colitis models induced by intravenous ipilimumab injection, with L. salivarius CCFM 1266 demonstrating superior effectiveness. This amelioration was characterized by an augmented ratio of Treg cells and M2 macrophages, a diminishment in pro-inflammatory cytokines (IL-1β, TNF-α, IFN-γ, IL-23), and an elevation in the anti-inflammatory cytokine IL-10. The ingestion of L. salivarius CCFM 1266 exerted a discernible influence on the composition of the gut microbiota. Untargeted metabolomics revealed an increase in colonic nicotinic acid levels following the administration of L. salivarius CCFM 1266, potentially initiating the activation of the colonic GPR109a pathway. This mechanism likely serves as the fundamental basis for the protective capacity of L. salivarius CCFM 1266 against ICB-induced colitis. Importantly, L. salivarius CCFM 1266 did not interfere with the anti-tumor immune response elicited by ipilimumab. Probiotic intervention thus emerges as a promising approach for alleviating ICB-induced colitis.

The strategy of using tumor cells to construct whole-cell cancer vaccines has received widespread attention. However, the limited immunogenicity of inactivated tumor cells and the challenge of overcoming immune suppression in solid tumors have hindered the application of whole-cell-based cancer immune therapy. Inspired by the regulatory effects of MnO 2 and spatiotemporal control capability of material layers in cell surface engineering, we developed a manganese (Mn)-mineralized tumor cell, B16F10@MnO 2 , by inactivating B16F10 melanoma cells with KMnO 4 to generate manganese-mineralized tumor cells. The cell-based composite was formed by combining amorphous MnO 2 with the membrane structure of cells based on the redox reaction between KMnO 4 and tumor cells. The MnO 2 layer induced a stronger phagocytosis of ovalbumin (OVA)-expressing tumor cells by antigen presenting cells than formaldehyde-fixed cells did, resulting in specific antigen-presentation in vitro and in vivo and subsequent immune responses. Intratumoral therapy with B16F10@MnO 2 inhibited B16F10 tumor growth. Moreover, the infiltration of CD8 + T cells within B16F10 solid tumors and the proportion of central memory T cells both increased in B16F10@MnO 2 treated tumor-bearing mice, indicating enhanced adaptive immunity. This study provides a convenient and effective method to improve whole-cell-based anti-tumor therapy.

Beyond three-dimensional (3D) architectures, polar semiconductor heterostructures are developing in the direction of two-dimensional (2D) scale with mix-dimensional integration for novel properties and multifunctional applications. Herein, we stacked 2D Janus MoSSe and 3D wurtzite GaN polar semiconductors to construct MoSSe/GaN polar heterostructures by polarity configurations. The structural stability was enhanced as binding energy changed from -0.08 eV/-0.17 eV in the N polarity to -0.24 eV/-0.42 eV in the Ga polarity. In particular, the polarity reversal of GaN in contact with Janus MoSSe not only determined the charge transfer direction but also significantly increased the electrostatic potential difference from 0.71 eV/0.78 eV in the N polarity to 3.13 eV/2.24 eV in the Ga polarity. In addition, strain modulation was further utilized to enhance interfacial polarization and tune the electronic energy band profiles of Janus MoSSe/GaN polar heterostructures. By applying in-plane biaxial strains, the AA and AA' polarity configurations induced band alignment transition from type I (tensile) to type II (compressive). As a result, both the polarity reversal and strain modulation provide effective ways for the multifunctional manipulation and facile design of Janus MoSSe/III-nitrides polar heterostructures, which broaden the Janus 2D/3D polar semiconducting devices in advanced electronics, optoelectronics, and energy harvesting applications.

Aging is characterized by a decline in biological functions, leading to various health issues. There is significant interest in mitigating age and age-related health issues. Gut microbiota has emerged as a crucial target for combating aging and influencing host health. This study evaluated the anti-aging effects of Lactiplantibacillus plantarum CCFM8661 in mice and the role of the gut microbiota in mediating its effects. Aging was induced in mice using D-galactose, and L. plantarum CCFM8661 was orally administered for 8 weeks to evaluate its effects on age-related decline and the gut microbiota. The results demonstrated that supplementation with L. plantarum CCFM8661 effectively alleviated cognitive impairment and oxidative stress in the aging brain, as well as liver oxidation and bone damage, and impaired intestinal barrier function in aging mice. Furthermore, L. plantarum CCFM8661 modulated the gut microbiota of aging mice, increasing the abundance of beneficial bacteria, such as Ruminococcaceae, and influenced the functionality of the gut microbiota to promote the production of active metabolites. These findings suggest that L. plantarum CCFM8661 has a mitigating effect on organismal aging, especially brain aging.

Monitoring the spatiotemporal dynamics of cancer biomarkers within the tumor microenvironment (TME) is critical to understanding their roles in tumorigenesis. Here, we reported a multifunctional fusion protein (collagen-binding domain and duck circovirus tag fused to mCherry, CBD-mCherry-DCV) capable of binding collagen with high affinity and covalently binding specific nucleic acids with exceptional efficiency. We then constructed a chimeric protein-nucleic acid nanodevice (CPNN) using CBD-mCherry-DCV and an aptamer-based sensing module to enable spatially controlled ratiometric imaging of cancer biomarkers in the TME. The collagen-anchoring module CBD-mCherry-DCV allowed specific immobilization of CPNN on 3D multicellular tumor spheroids, enabling the sensing module to achieve "off-on" fluorescence imaging of cancer biomarkers upon specific target recognition by an aptamer. Taking advantage of the constant fluorescence signal of mCherry and the activatable fluorescence response of Cy5 to specific cancer biomarkers, the detection sensitivity and reliability of CPNN were improved by self-calibrating the signal intensity. Specifically, CPNN enabled ratiometric fluorescence imaging of varying concentrations of exogenous PDGF-BB and ATP in tumor spheroids with a high signal-to-background ratio. Furthermore, it allowed the visual monitoring of endogenous PDGF-BB and ATP released from cells. Overall, this study demonstrates the potential of the nanodevice as a versatile approach for the visualization and imaging of cancer biomarkers in the TME., Competing Interests: The author(s) declare that they have no competing interests., (This journal is © The Royal Society of Chemistry.)

Electrocatalysis is involved in many energy storage and conversion devices, triggering research and development of electrocatalysts, particularly single-atom catalysts (SACs). The introduction of the strain effect to enhance the performance of SACs has drawn ever-increasing research attention, which can tailor the local atomic and electronic structure of active sites. Herein, via high throughput calculations, we have explored the effects of strain on the catalytic performance of SACs with MN 4 configuration for electrochemical reactions of N 2 and O 2 by incorporating d- and p-block single metal atoms into BN nanocages (BNNCs). The calculations demonstrate that Os@BNNC exhibits the highest catalytic activity for the nitrogen reduction reaction (NRR) with a limiting potential of -0.29 V. Co@BNNC can serve as an excellent bifunctional SAC for the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER), with overpotentials of 0.32 and 0.37 V, respectively. In particular, Sn@BNNC with a p-block metal as the active center is a competitive SAC for the ORR with an overpotential of 0.64 V. More interestingly, the NRR and ORR performances of SACs supported by BNNCs have a close correlation with the structural and electronic properties of adsorbed N 2 and O 2 molecules, which proves that controlling the adsorption energy of N 2 and O 2 molecules is crucial to improving the catalytic activity of BNNC. The current investigation opens up an avenue for designing SACs embedded in nanocages possessing intrinsically curved surfaces for electrochemical reactions.

The rapid recombination of photogenerated carriers of photocatalysts greatly limits their actual application in CO 2 conversion into valuable chemicals. Herein, dual CuO x and MnO x cocatalysts are decorated on g-C 3 N 4 nanosheets via a one-step photodeposition strategy. Benefiting from the repulsion between Cu 2+ and Mn 2+ cations, a novel g-C 3 N 4 -based heterostructure loaded with spatially separated CuO x and MnO x nanoparticle dual cocatalysts has been successfully fabricated. Cu favors the trapping of electrons, while MnO x tends to collect holes. Moreover, the Cu 2 O/g-C 3 N 4 p-n heterojunction also accelerates the charge separation. As a result, the photogenerated holes and electrons flow into and out of the photocatalyst, respectively, resulting in enhanced charge separation for achieving efficient CO 2 photoreduction over CuO x /g-C 3 N 4 /MnO x . Accordingly, the optimized CuO x /g-C 3 N 4 /MnO x exhibits an improved CO production rate of 5.49 μmol g -1 h -1 , which is 27.5 times higher than that of bare g-C 3 N 4 .

Clinical antibiotics used worldwide could diminish the intestinal barrier, enhance contact with microbiota and intestinal immune cells, and induce inflammation. We found that ciprofloxacin treatment of Salmonella enterica serovar Typhimurium infection resulted in the destruction of the intestinal barrier, with decreased concentrations of MUC2, ZO-1, and occludin in the jejunum and colon. Ganoderma lucidum ethanol extracts (GLE), as a prebiotic food extract, significantly decreased inflammation-related enzymes, including COX-2, MPO, and iNOS, and pro-inflammatory cytokines (IL-6, IL-1β, IL-17, and TNF-α), and protected the intestinal barrier by increasing the concentration of MUC2, ZO-1, and occludin. Meanwhile it significantly increased the abundances of Salmonella , Parabacteroides , Acinetobacter , Enterococcus , and Escherichia-Shigella , which increased the risk of pathogenic bacterial infections. Prebiotic G. lucidum polysaccharide (GLP) provided a significant intestinal barrier, improving the concentration of ZO-1, occludin, and MUC2 in the colon and jejunum. The synergistic effects of GLP and ciprofloxacin were hypothesized to reverse the negative effects resulting from ciprofloxacin alone, as the concentrations of ZO-1, occludin, and MUC2 were significantly increased in the jejunum and colon, especially in the colon. Also, the synergistic effect increased the abundances of probiotic bacteria Lachnospiraceae NK4A136, Ruminococcaceae UGG-014, Lactobacillus , and Parabacteroides . In conclusion, combined GLP and ciprofloxacin therapy against Salmonella infection alleviated the side effects resulting from the clinical application of the antibiotic alone, and increased the probiotic bacterial population.

It is well known that diet is one of the most important factors in shaping the host's intestinal microbiota. Lactobacillus, a common group of probiotic bacteria, is widely distributed in the host gut, and studies have linked changes in lactobacilli in the gut to differences in dietary habits. Different dietary habits may affect not only the structural composition but also the function of lactobacilli in the intestine. Therefore, we dissected 283 metagenomes from samples collected from individuals with different dietary habits, investigating the presence of different species of lactobacilli. We demonstrated that the highest abundance of lactobacilli was found in stool samples from omnivorous populations and that Ligilactobacillus ruminis ( L. ruminis ) and Lactiplantibacillus plantarum ( L. plantarum ) were more prevalent in these samples than in vegetarian and vegan samples. In addition, we determined that different dietary structures affected the functional potential of lactobacilli by reconstructing the metagenome-assembled genomes (MAGs) of L. ruminis (highest abundance) in the samples. L. ruminis strains associated with a vegetarian diet had a higher "replication, recombination and repair" functional potential and may also have a greater capacity for glutathione (GSH) synthesis and metabolism. The results of our analysis provide evidence for the possibility of a specific selection of lactobacillus strains for people with different dietary habits.

Green fluorescent proteins (GFPs) are useful and essential biomolecules that have revolutionized biosensor research. Researchers have extensively utilized GFPs for designing fluorescence biosensors due to their intrinsic fluorescence, high stability, and ability to undergo permutation or mutation. This review provides a concise summary of recent advancements in developing GFP-based biosensors. The construction approaches for GFP-based biosensors can be categorized into four types: (1) single GFP-based biosensors; (2) fluorescence resonance energy transfer-based biosensors; (3) GFP-based split biosensors; and (4) GFP chromophore analogy-based biosensors. We highlight the applications of these sensors in biomolecule detection and life sciences, while also sharing personal insights into the challenges associated with GFP-based biosensors and proposing future research directions.

Morchella esculenta polysaccharides exhibit numerous probiotic activities, but their regulatory effects on the gut microbiota are unclear. This study was conducted to explore whether M. esculenta polysaccharides can regulate dysbacteriosis caused by a high-fat diet and relieve obesity. We extracted a water-soluble polysaccharide from M. esculenta (MPF, purity: 96.19%, consisting of 55.97% glucose, 9.63% xylose, and 22% mannose) that reduces mouse fat accumulation, alleviates obesity, and relieves liver injury, after 90 days of high-fat diet intake. This polysaccharide reversed dysbiosis and regulated the abundance of gut microbiota caused by a high-fat diet (restoring the ratio of Firmicutes/Bacteroidetes and changing the abundances of Lactobacillus , Dubosiella , and Faecalibaculum ), increasing short-chain fatty acids and decreasing gene expression in the liver ( glucose 6-phosphatase , glucose transporter 1 , peroxisome proliferator-activated receptor gamma ( PPAR ) receptor-1α , PPARα , PPARγ , and CCAAT enhancer binding protein α ). We identified a regulatory relationship between polysaccharides, gut microbiota, and the liver as a potential mechanism by which polysaccharides can alleviate obesity.

Resistant starch (RS) has the ability to improve the structure of the gut microbiota, regulate glucolipid metabolism and maintain the health of the human body, and has been extensively studied by many scholars in recent years. However, previous studies have provided a wide range of results on the differences in the gut microbiota after RS intake. In this article, we performed a meta-analysis of a total of 955 samples of 248 individuals from the seven studies included to compare the gut microbiota of the baseline and the end-point of RS intake. At the end-point, RS intake was related to a lower gut microbial α-diversity and higher relative abundance of Ruminococcus , Agathobacter , Faecalibacterium and Bifidobacterium , and the functional pathways of the gut microbiota related to the carbohydrate metabolism, lipid metabolism, amino acid metabolism and genetic information processing were higher. Different types of resistant starch and different populations led to varied responses on the gut microbiome. The altered gut microbiome may contribute to improve the blood glucose level and insulin resistance, which may be a potential treatment route for diabetes, obesity and other metabolic diseases.

Background : Patients with Parkinson's disease (PD) demonstrate intestinal dysbiosis and substantial gastrointestinal dysfunction. Preliminary evidence suggests that probiotics may have a positive effect on the motor and non-motor symptoms of PD. However, the effectiveness of probiotics in treating PD remains unclear. Therefore, a randomized controlled trial (RCT) was performed to examine the efficacy of oral probiotics in PD treatment. Methods : PubMed, Web of Science, Cochrane Library, EMBASE, Clinical Trials, and Google Scholar were searched for relevant RCTs published until January 28, 2023. Meta-analyses have examined the effects of probiotics on motor and non-motor symptom parameters in RCTs. Inverse-variance random or fixed effects were used to pool data. The Grading of Recommendations Assessment, Development, and Evaluations was used to examine the quality of evidence for outcomes of the meta-analysis. Results : Nine eligible RCTs ( N = 663) were included in this meta-analysis. In the meta-analysis, probiotic treatment significantly improved motor symptoms (UPDRS-III scores: standardized mean difference [SMD] = -0.28, 95% confidence interval [CI], -0.49 to -0.07, I 2 = 7%), constipation and constipation-related quality of life (Bristol scores: SMD = 0.54; 95% CI, 0.35 to 0.73, I 2 = 0%; bowel movement scores: SMD = 0.83; 95% CI, 0.59 to 1.07, I 2 = 43%; CSBMs: SMD = 0.56; 95% CI, 0.30 to 0.82, I 2 = 0%; PAC-QCL scores: SMD = -0.84; 95% CI, -1.08 to -0.60, I 2 = 0%), and anxiety and depression parameters (HAMA scores: SMD = -0.35; 95% CI, -0.60 to -0.10, I 2 = 0%; HADM-17 scores: SMD = -0.33; 95% CI, -0.59 to -0.08, I 2 = 0%). In addition, probiotic supplements significantly reduced the use of laxatives (SMD = -0.27; 95% CI, -0.53 to -0.01, I 2 = 15%) and increased GSH levels in the serum of PD patients (SMD = 0.52; 95% CI, 0.14 to 0.90, I 2 = 0%). The certainty of evidence was graded as very low for UPDRS-III, PAC-QCL, CSBMs, HAMA, HADM-17 and Bristol scores and low for bowel movement scores. Two of the nine RCTs reported that probiotics may cause abdominal bloating at low rates on consuming probiotics, which suggests that we should pay attention to the occurrence of adverse events during the consumption of probiotics in future studies. Conclusion : Oral probiotic consumption significantly improved motor symptoms, gastrointestinal dysfunction, anxiety, and depression in patients with PD. Notably, oral probiotics also reduced the use of laxatives and increased GSH levels in the serum of patients with PD. In future studies, more high-quality evidence from large-scale RCTs is needed to determine the exact effects of probiotic treatment on PD.

This study describes the influence of Lactobacillus plantarum CCFM8610 on the host by employing transcriptome and untargeted metabolomics. According to the enrichment analysis, three pathways, including the complement and coagulation cascade pathway, antigen processing and presentation pathways, and protein processing in the endoplasmic reticulum pathway, were affected by L. plantarum CCFM8610 colonization. According to partial least squares-discriminant analysis, five metabolites, L-methionine, D-tryptophan, indoleacrylic acid, DL-acetylcarnitine, and L-norleucine, were identified as key metabolites in the serum. Furthermore, integrative analysis of the metabolome and transcriptome revealed connections between enriched pathways and differential metabolites, and the regulation strategy of choline by affecting gene expression was proposed. Overall, the effects of L. plantarum CCFM8610 on host health were investigated after excluding the influence of gut microbes, which provides a valuable reference for studying the potential mechanisms of the effect of probiotics on host health.

Probiotics have been evaluated as alternative approaches for preventing the relapse of Crohn's disease (CD). Previously, we observed strain-specific anti-inflammatory properties of Bifidobacterium bifidum in 2,4,6-trinitrobenzene sulfonic acid (TNBS) acute colitis models. In this study, we further assessed the effects of several B. bifidum strains on colonic damage, fibrosis, inflammatory factors, intestinal microbial and metabolic profiles, and peripheral regulatory T cells (Tregs) in the context of TNBS chronic colitis in mice. These results indicated that B. bifidum FJSWX19M5, but not FXJWS17M4, ameliorated body weight loss, reduced colonic shortening and injury, decreased markers of gut inflammation, and rebalanced colonic metabolism in TNBS-treated mice. FJSWX19M5 supplementation also promoted Treg cell differentiation and intestinal barrier restoration compared to other strains. All living B. bifidum strains (FJSWX19M5, FXJWS17M4 and FHENJZ3M6) seemed to restore the disruption of the gut microbiota caused by TNBS. The co-culture of B. bifidum strains and mesenteric lymph node cells from TNBS-treated mice showed that those strains with anti-colitis could induce higher IL-10 levels and a lower ratio of IL-22/IL-10 and IL-17/IL-10 when compared to those strains that were not protective. Furthermore, heat-killed FJSWX19M5 exhibited a relief effect on colitis-related symptoms (including body weight loss, colonic shortening and injury). These data imply that specific B. bifidum strains or their lysates may be the current therapeutic alternatives for CD.

Doxorubicin (DOX) has been an emerging environmental pollutant due to its significant genotoxicity to mankind. Advanced oxidation processes are a potential strategy to remove DOX in water solution. To develop a highly efficient catalytic agent to remove DOX, bimetal MOFs were synthesized, with Cu 2+ and Co 2+ as the central ions and adenine as the organic ligand. This study investigated the degradation of DOX by Co/Cu-MOFs combined with peroxymonosulfate (PMS). It was found that the degradation of DOX by Co/Cu-MOFs can reach 80% in only 10 seconds. This can be explained by the charge transfer from Co(iii) to Co(ii) being accelerated by Cu 2+ , resulting in the rapid generation of free radicals, which was proved by the EIS Nyquist diagram. Co/Cu-MOFs can be reused by simply washing with water without inactivation. Therefore, Co/Cu-MOFs can be used as an efficient catalytic agent to degrade DOX in environmental water., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

In 2013, Limosilactobacillus fermentum was regarded as a "generally recognized as safe" organism by the US Food and Drug Administration, and emerging evidence showed that it can exert beneficial health effects on humans. In this study, five L. fermentum strains from different phylogroups of a phylogenetic tree containing 224 L. fermentum strains were chosen, and their protective effects against loperamide-induced constipation in mice were studied. Animal experiments showed that L. fermentum YN54 significantly alleviated weight loss, increased fecal moisture, accelerated intestinal peristalsis, and increased the small intestinal transit rate in mice with constipation by regulating gastrointestinal peptides and increasing the amount of intestinal short-chain fatty acids. However, the other four L. fermentum strains (XJ61, CECT5716, WX115, and GD121) did not relieve constipation in mice treated with loperamide. A comparative genomic analysis of these strains was conducted and " L. fermentum YN54 only" genes were functionally annotated and validated with the other three L. fermentum strains (FJ12, GX51, and ZH1010) that had different functional genes. Finally, the genes involved in the synthesis of fatty acid hydrase, polysaccharides, and cell membranes were identified to be associated with the probiotic effect of L. fermentum on mice with constipation through preliminary experiments in this study.

Bacillus coagulans ( B. coagulans ) can improve and prevent functional gastrointestinal disorders. However, there has been little discussion in the literature on the difference between spores and vegetative cells for relieving constipation. The purpose of this study was to determine the efficacy of Bacillus coagulans ( B. coagulans ) vegetative cells and spores against loperamide-induced constipation in mice. According to our findings, B. coagulans vegetative cells and spores differ in their ability to relieve loperamide-induced constipation. Two of the three strains of B. coagulans spores used in this experiment, B. coagulans GBI-30 6086 and B. coagulans 90, were significantly different from the model group in relieving constipation. This mainly manifested as a decreased time required for first black stool defecation (by 52 and 79 min, respectively), and increased counts of the first black stools in 5 h (by 15 and 8, respectively), the small intestine transit rate (by 23.31% and 20.52%, respectively), and the concentration of SCFAs. While the administration of vegetative cells could only relieve some indicators of intestinal transit disorders and dysbacteriosis caused by constipation. Spores of B. coagulans GBI-30 6086 and B. coagulans 90 had higher survival rates in the simulated gastrointestinal tract environment, which indicated that the functional modes of the three strains were different and had a strong relationship with the morphology of the bacteria. B. coagulans GBI-30 6086 and B. coagulans 90 spores alleviate constipation by increasing the abundances of Actinobacteria, Deferribacteres, and Lachnospiraceae UCG-006 (which were positively correlated with SCFAs) and decreasing the abundances of Cyanobateria and Rikenellaceae _RC9_gut group (which were negatively correlated with SCFAs) and the levels of Ruminococcaceae UGC-014 and Alistipes . In this study, the effects of probiotics in the form of spore or vegetative cell were compared, and the optimal preparation form was determined, providing a theoretical basis for the application of probiotics of B. coagulans to relieve constipation.

A novel fluorescent probe L with a rhodamine B lactam structure modified with 3-methyl-2-thiophenecarboxaldehyde has been prepared based on the thiophilicity of Hg 2+ . The probe L exhibits a unique response with an "off-on-type" mode towards Hg 2+ among other biologically relevant metal cations. The limit of detection (LOD) for probe L is 1.5 ppb. In addition, in the presence of Hg 2+ , the probe L shows a colorimetric response from colorless to pink. The recognition behavior of probe L towards Hg 2+ has been investigated by 1 H NMR titration experiments, Job's plot, and MS and IR analyses. As a result, the ligation between the probe and Hg 2+ leads to the scission of the spirolactam bond of free L and the restoration of its conjugated structure, which can give rise to the fluorescence enhancement of the probe L. Besides, it also can be used as a sensitivity probe in living cells for Hg 2+ sensing, which can meet various needs in genetic and environmental samples., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Wrinkles are commonly observed in uniaxially stretched hyperelastic membranes and eventually disappear with the increase of stretching. The widely used scheme at present assumes the material parameters to be empirical values and straightforwardly considers some constitutive models to explore the wrinkling and restabilization behavior. However, this simple treatment may cause deviation from experiment by ignoring the applicability of the models and the authenticity of the input parameters, prompting us to report based on realistic material parameters. This paper presents an experimental, theoretical and numerical investigation on the wrinkling and restabilization behavior of hyperelastic materials. By fitting experimental stress-strain curves of PDMS films, we confirm that the 3-term Ogden model bears a closer resemblance to the experimental data than the widely used neo-Hookean, Mooney-Rivlin, and Arruda-Boyce models under certain circumstances. The simulation results indicate that different constitutive models quantitatively affect the critical buckling strain, wrinkling amplitudes, and restabilization points. Furthermore, the isolated central bifurcation point solved by Koiter stability theory agrees well with the simulation and experimental results. A 3D phase diagram of stability boundaries was established to gain a comprehensive insight into the effects of geometric parameters (length, width, and thickness) on wrinkling.

KSiH 3 exhibits 4.1 wt% experimental hydrogen storage capacity and shows reversibility under moderate conditions, which provides fresh impetus to the search for other complex hydrides in the K-Si-H system. Here, we reproduce the stable Fm 3̄ m phase of K 2 SiH 6 and uncover two denser phases, space groups P 3̄ m 1 and P 6 3 mc at ambient pressure, by means of first-principles structure searches. We note that P 3̄ m 1-K 2 SiH 6 has a high hydrogen content of 5.4 wt% and a volumetric density of 88.3 g L -1 . Further calculations suggest a favorable dehydrogenation temperature T des of -20.1/55.8 °C with decomposition into KSi + K + H 2 . The higher hydrogen density and appropriate dehydrogenation temperature indicate that K 2 SiH 6 is a promising hydrogen storage material, and our results provide helpful and clear guidance for further experimental studies. We found three further potential hydrogen storage materials stable at high pressure: K 2 SiH 8 , KSiH 7 and KSiH 8 . These results suggest the need for further investigations into hydrogen storage materials among such ternary hydrides at high pressure.

A three-dimensional crosslinked CFs@CNT/CoS x nanocomposite was successfully synthesized by in situ growing carbon nanotubes on carbon nanofibers and a facile sulfurization process. The carbon nanotubes synthesized by sintering melamine under the catalysis of cobalt can increase the specific surface areas and provide abundant sodium ion diffusion channels for the composite. Meanwhile, the formed cobalt sulfide nanoparticles will increase the active sites on the surface of CFs@CNT/CoS x . Due to the rational design of the composite structure, such an anode can deliver a specific capacity of 423.7 mA h g -1 after 100 cycles at 100 mA g -1 and exhibit superior rate performance of retaining 324.1 mA h g -1 at 2 A g -1 for sodium storage.

Functional nanoparticles (NPs) hold immense promise in diverse fields due to their unique biological, chemical, and physical properties associated with size or morphology. Microfluidic technologies featuring precise fluid manipulation have become versatile toolkits for manufacturing NPs in a highly controlled manner with low batch-to-batch variability. In this review, we present the fundamentals of microfluidic fabrication strategies, including mixing-, droplet-, and multiple field-based microfluidic methods. We highlight the formation of functional NPs using these microfluidic reactors, with an emphasis on lipid NPs, polymer NPs, lipid-polymer hybrid NPs, supramolecular NPs, metal and metal-oxide NPs, metal-organic framework NPs, covalent organic framework NPs, quantum dots, perovskite nanocrystals, biomimetic NPs, etc. we discuss future directions in microfluidic fabrication for accelerated development of functional NPs, such as device parallelization for large-scale NP production, highly efficient optimization of NP formulations, and AI-guided design of multi-step microfluidic reactors.

A sequentially responsive nanocarrier was fabricated with three-in-one functional integration: bio-imaging, tumor microenvironment responsive chemotherapy and cascade activation of upconversion photodynamic therapy. The designed DNA outer nanoshell displayed site-specific degradation and controlled degradation speed. Significantly, the developed controllable nanotheranostic agent displayed high cell apoptosis ratios and obvious tumor inhibition.

Bacteroides fragilis , one of the potential next-generation probiotics, has been demonstrated to alleviate inflammation-associated diseases. In this study, we compare the anti-inflammatory effects of six Bacteroides fragilis strains on systemic inflammation and link their strain-specific characteristics, both physiologically and genetically, to their function. A lipopolysaccharide (LPS)-induced systemic inflammation model in mice was used as an in vivo model to compare the effects of different B. fragilis strains. Short-chain fatty acids (SCFAs) were measured by gas chromatography-mass spectrometry (GC-MS). The in vitro immunomodulatory properties were evaluated in LPS-stimulating RAW264.7 cell lines. Orthologous gene clusters were compared using OrthoVenn2. The results indicate a strain-specific in vitro anti-inflammatory effect. Effective strains induce higher colon SCFAs in vivo and interleukin-10 (IL-10) production in vitro . Comparative genomic analysis showed that the SCFA-inducing strains possess three genes relating to carbohydrate metabolism (GH2, GH35 families) and binding and transportation ( SusD ), all of which are associated with niche fitness and expansion. IL-10-inducing strains share a highly similar gene, wbjE , which may result in a distinct O-antigen structure of LPS and influence their immunomodulatory properties. B. fragilis is strain-specific against LPS-induced systemic inflammation in mice. The beneficial effects of a specific strain may be attributed to its SCFA and IL-10 inducing abilities. Strain-specific potential genes can be excavated to link these differences.

Developing highly sensitive and selective methods for Cu 2+ detection in living systems is of great significance in clinical copper-related disease diagnosis. In this work, a near infrared (NIR) fluorescent probe, CySBH, with a salicylaldehyde benzoyl hydrazone group as a selective and sensitive receptor for Cu 2+ was designed and synthesized. The specific coordination of the salicylaldehyde benzoyl hydrazone group in CySBH with Cu 2+ can induce a distinct quench of the fluorescence intensity, allowing for real-time tracking of Cu 2+ . We have demonstrated that CySBH could rapidly recognize Cu 2+ with good selectivity and high sensitivity. Moreover, on the basis of low cell cytotoxicity, the probe was used to visualize Cu 2+ in two cell lines by fluorescence imaging. Furthermore, CySBH can also be used to monitor Cu 2+ in vivo due to its NIR emission properties. These overall results illustrate that the NIR fluorescent probe CySBH provides a novel approach for the selective and sensitive monitoring of Cu 2+ in living systems., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Inflammatory bowel disease is associated with intestinal homeostasis dysregulation and gut microbiota dysbiosis. This study aimed to investigate the protective effect of Ganoderma applanatum extracts ( G. applanatum polysaccharides (GAP) and 75% ethanol extracts (GAE)) on colon inflammation and elucidate the therapeutic mechanism. GAP and GAE showed considerable protective effects against dextran sodium sulfate (DSS)-induced colitis, as demonstrated by reduced mortality, body weight, disease activity index score, colon length, and histological score. Through GAP and GAE administration, the destroyed intestinal barrier recovered to normal, as did intestinal inflammation. We also confirmed that GAP administration promoted the recovery of colitis in a gut microbiota-dependent manner. The similarity between GAP and GAE administration was that they both altered the disordered gut microbiota damaged by DSS, exhibiting reduced abundance of Escherichia _ Shigella , Enterococcus , and Staphylococcus , but the modulation of the gut microbiota was distinct between GAP and GAE.

As a class of important carbon nanomaterial, carbonized polymer dots (CPDs), also called carbon dots (CDs), have aroused wide interest owing to their unique water solubility, fluorescence properties, and rich surface functional groups. However, the directional tuning of the fluorescence properties of CPDs remains incomplete because of the influence of many factors like diameter, solvent and surface groups. Particularly, most carbonized polymer dots are synthesized in a neutral pH environment. Herein, by modulating the pH (strongly acidic or alkaline) of dextrin water solution, bicolor fluorescence emission (blue and yellow) CPDs were prepared by a hydrothermal reaction. Through systematic characterization, it was found that the different fluorescence properties are regulated by the diameters and surface groups of the carbon cores. Simultaneously, the pH value affected the nucleation process. Based on the excellent fluorescence properties, cell fluorescence imaging and cytotoxicity were tested. The bicolor fluorescence CPDs obtained by tuning the pH provide an important theoretical basis for the design of broadband CPDs., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Constructing a theranostic agent for high-contrast multimodality imaging-guided synergistic therapy with long-term tumor retention and minimum systemic side effects still remains a major challenge. Herein, a hybrid microbubble-based theranostic platform was developed for dual-modality ultrasound (US) and enhanced photoacoustic (PA) imaging-guided synergistic tumor therapy by combining starvation therapy, low-temperature photothermal therapy (PTT), and hypoxia-activated therapy, based on polydopamine (PDA) doped poly(vinyl alcohol) microbubbles loaded with glucose oxidase (GOx) (PDA-PVAMBs@GOx) and hypoxia-activated prodrug (HAP) tirapazamine (TPZ). For dual-modality US/enhanced PA imaging, PDA-PVAMBs provided 6.5-fold amplified PA signals relative to freely dispersed PDA nanoparticles (PDA NPs). For synergistic cancer therapy, oxygen (O 2 ) carried by PDA-PVAMBs@GOx was first released to promote starvation therapy by loaded GOx. Then, moderate near-infrared (NIR) laser irradiation triggered PTT and improved enzymatic activity of GOx with its optimal activity around 47 °C. Subsequently, GOx-mediated tumor starvation depleted O 2 and exacerbated the hypoxia environment, thereby activating the toxicity of TPZ in the tumor site. Through dual-modality US/PA imaging monitoring, PDA-PVAMBs@GOx with long-term retention (∼7 days) combined with PTT and TPZ significantly inhibited the growth of solid tumors with minimum systemic side effects, which might be a powerful tool for effective tumor treatment.

Integrating metal-organic frameworks (MOFs) of different components or structures together and exploiting them as electrochemical sensors for electrochemical sensing has aroused great interest. Furthermore, the incorporation of noble metals with MOFs is conducive to the improvement of catalytic performance. In this work, Pd@UiO-66-on-ZIF-L nanomaterials were successfully synthesised onto a self-supported flexible carbon cloth (Pd@UiO-66-on-ZIF-L/CC) through a novel strategy called MOF-on-MOF. Then, Au nanoparticles were electrodeposited onto Pd@UiO-66-on-ZIF-L/CC to obtain Au-Pd@UiO-66-on-ZIF-L/CC, which can serve as an excellent electrocatalyst for the reduction of hydrogen peroxide (H 2 O 2 ). The obtained flower-like Pd@UiO-66-on-ZIF-L/CC hybrid MOF changes the structure of the monomeric MOF alone and adds more attachment sites. The synergy of the bimetals greatly improved the catalytic performance of the as-developed sensor. Electrochemical experiment results show that the proposed sensor based on Au-Pd@UiO-66-on-ZIF-L/CC has an extended linear range from 1 μM to 19.6 mM with a sensitivity of 390 μA mM -1 cm -2 , and a low limit of detection (LOD) of 21.2 nM ( S / N = 3). Moreover, it has good anti-interference, reproducibility, repeatability and excellent stability. Furthermore, the real-time in situ detection of H 2 O 2 secreted from human adenocarcinomic alveolar basal epithelial cells (A549 cells) was achieved by culturing cells on Au-Pd@UiO-66-on-ZIF-L/CC, which indicates the potential of the sensor for applications in cancer pathology. Both the synthesis strategy and the sensor design provide new methods and ideas for the production of ultrasensitive H 2 O 2 electrochemical sensors.

In this study, yttrium-doped CH 3 NH 3 PbI 3 (Y-MAPbI 3 ) and pure CH 3 NH 3 PbI 3 (MAPbI 3 ) perovskite films have been fabricated using a one-step solution spin coating method in a glove box. X-ray diffractometry and field-emission scanning electron microscopy were used to characterize the crystal structures and morphologies of perovskite films, respectively. It was found that the orientation of the crystal changed and the grains became more uniform in Y-MAPbI 3 film, compared with the pure MAPbI 3 perovskite film. The films were used to prepare the resistive switching memory devices with the device structure of Al/Y-MAPbI 3 (MAPbI 3 )/ITO-glass. The memory performance of both devices was studied and showed a bipolar resistive switching behavior. The Al/MAPbI 3 /ITO device had an endurance of about 328 cycles. In contrast, the Al/Y-MAPbI 3 /ITO device exhibited an enhanced performance with a long endurance up to 3000 cycles. Moreover, the Al/Y-MAPbI 3 /ITO device also showed a higher ON/OFF ratio of over 10 3 , long retention time (≥10 4 s), lower operation voltage (±0.5 V) and outstanding reproducibility. Additionally, the conduction mechanism of the high resistance state transformed from space-charge limited current for a Y free device to the Schottky emission after Y doping. The present results indicate that the Al/Y-MAPbI 3 /ITO device has a great potential to be used in high-performance memory devices.

A bifunctional cinchona squaramide catalyzed enantioselective aza-Friedel-Crafts reaction between 2-naphthols and benzothiazolimines has been developed, and a series of chiral 2'-aminobenzothiazolomethyl naphthols with potential antiproliferative and anthelmintic activities have been successfully and effectively prepared in good to excellent yields (up to 98%) with excellent enantioselectivities (up to >99% ee) even in a scale-up preparation under mild conditions.

For studying protein-protein interactions (PPIs) in general, a powerful and commonly used technique is conventional coimmunoprecipitation (co-IP/pulldown) followed by western blotting. However, the technique does not provide precise information regarding the kinetics and stoichiometry of PPIs. Another drawback is that the sensitivity of conventional co-IP is not suitable for examining PPIs in rare cells such as sensory hair cells, circulating tumor cells, embryonic stem cells, and subsets of immune cells. The current single-molecule pulldown (SiMPull) assay can potentially be used for studying PPIs in rare cells but its wide application is hindered by the high technical barrier and time consumption. We report an innovative, agarose microbead-based approach for SiMPull. We used commercially available, pre-surface-functionalized agarose microbeads to capture the protein of interest together with its binding partners specifically from cell extracts and observed these interactions under a microscope at the single-molecule level. Relative to the original method, microbead-based SiMPull is considerably faster, easier to use, and more reproducible and yet provides similar sensitivity and signal-to-background ratio; specifically, with the new method, sample-preparation time is substantially decreased (from ∼10 to ∼3 h). These crucial features should facilitate wide application of the powerful and versatile SiMPull method in common biological and clinical laboratories. Notably, by exploiting the simplicity and ultrahigh sensitivity of microbead-based SiMPull, we used the method in the study of rare auditory hair cells and γδ T cells for the first time.

Research studies have shown that Lactobacillus fermentum generally exists in the human gut and has potential health benefits on host health due to its antimicrobial and antioxidant properties. However, the lack of an effective culture medium for the isolation of L. fermentum has presented a significant obstacle on the path to screen L. fermentum strains from the human intestinal tract with a large diversity of commensal microbes. In this study, a total of 51 Lactobacillus species are detected in 200 human fecal samples and we aim to distinguish L. fermentum from these common existing Lactobacillus species and design a more efficient culture medium for isolating L. fermentum strains from the human gut. Based on antibiotic susceptibility and sugar utilization tests, a new optimized medium called LFMATA containing arabinose as the carbon source and 20 mg L-1 vancomycin, 64 mg L-1 gentamicin and 256 mg L-1 streptomycin was developed. Genotype and phenotype analysis for antibiotic resistance and carbohydrate metabolism showed that though glycometabolism-related genes (araA, xylA, manX, bglX, treP and rbsK) correlated with the carbon utilization of Lactobacillus, the genes conferring resistance to streptomycin (gidB and rpsL) and gentamicin (tlyA) were not directly associated with the antibiotic resistance of Lactobacillus strains. This new selective medium greatly increased the efficiency of screening L. fermentum strains from human fecal samples, with the rate of L. fermentum isolation on LFMATA being 10-fold higher than that on LAMVAB.

The role of supplementation with different Bacteroides fragilis (B. fragilis) strains in alleviating ulcerative colitis (UC) is unclear due to the controversial results from animal experiments. In this study, three B. fragilis strains were evaluated for their ability to alleviate dextran sulfate sodium (DSS)-induced UC in C57BL/6J mice. We analyzed the anti-inflammatory effects of different B. fragilis strains and the changes they caused in the intestinal microbiota composition, intestinal epithelial permeability, cytokine concentrations, protein expression of nuclear factor kappa-B (NF-κB) and the underlying specific genes. The results showed that when orally administered, the different B. fragilis strains exerted different effects on the assessed parameters of the mice. The results of real-time quantitative polymerase chain reaction and immunofluorescence staining showed that the supplementation of B. fragilis FSHCM14E1, but not FJSWX11BF, enhanced the expression of the tight-junction proteins ZO-1, occludin and claudin-1. Western blot analysis showed that the anti-inflammatory effects of B. fragilis FSHCM14E1 were related to the NF-κB pathway. Genomic analysis suggested that the anti-inflammatory effects of FSHCM14E1 may be mediated through specific genes associated with defense mechanisms and the secretion of SCFAs. Overall, this study indicates the therapeutic potential of B. fragilis FSHCM14E1 for the prevention of UC.

Bifidobacterium longum (B. longum) species are widely used to prevent and treat ulcerative colitis (UC). In this study, phylogenetic and pan-genomic characterization of 122 B. longum strains was performed on the basis of 936 core genes; among these, four strains from different branches of the phylogenetic tree were selected for an evaluation of anti-inflammatory and immune modulatory activities in a DSS-induced colitis mouse model. Among the tested B. longum strains (B. longum FBJ20M1, B. longum FGDLZ8M1, B. longum FGSZY16M3, and B. longum FJSWXJ2M1), B. longum FGDLZ8M1 was found to most effectively alleviate colitis by reducing the expression of pro-inflammatory cytokines, restoring the colon length, and maintaining the mucosal integrity. The anti-inflammatory mechanisms of B. longum FGDLZ8M1 were related to the inhibition of NF-κB signaling. Genomic analysis indicated that these protective effects of B. longum FGDLZ8M1 may be related to specific genes associated with carbohydrate transport and metabolism and defense mechanisms (e.g., tolerance to bile salts and acids). Correlation analysis indicated that gastrointestinal transit tolerance was the most strongly associated factor. Our findings may contribute to the rapid screening of lactic acid bacterial strains with UC-alleviating effects.

Preliminary evidence shows the potential role of probiotics in ameliorating multiple sclerosis (MS); however, the effects of probiotics on MS remain unclear. Therefore, the aim of this study was to evaluate the efficacy of probiotics on multiple sclerosis by systematically reviewing the preclinical trials (animal trials) and performing meta-analysis of randomized controlled trials. PubMed, Web of Science, Cochrane central of randomized clinical trials, EMBASE, Clinical Trials, and a search engine Google Scholar were systematically searched and manually screened updated to November 2020, resulting in eligible 3 randomized controlled trials (RCTs) and 22 preclinical studies. Meta-analysis of RCTs enrolling 173 patients with MS receiving probiotics revealed significant beneficial effects of probiotic supplementation on mental health (expanded disability status scale scores: standardized mean difference [SMD] = -1.22; I 2 = 92%; 95% CI, -2.40 to -0.03, P = 0.04; Beck depression inventory total scores: SMD = -1.58; I 2 = 94%; 95% CI, -3.03 to -0.12; P = 0.03; general health questionnaire scores: SMD = -0.71; I 2 = 0%; 95% CI, -1.02 to -0.40; P < 0.00001; depression anxiety and stress scale scores: SMD = -0.72; I 2 = 0%; 95% CI, -1.12 to -0.33; P = 0.0003), with very low certainty of evidence. In addition, probiotic intake markedly improved insulin resistance and inflammatory and oxidative stress markers. Preclinical studies have shown that probiotic consumption reduces the incidence and severity of MS, delays MS progression (15 studies), and improves motor impairment (3 studies) with favorable alterations of immune and inflammatory markers (20 studies) and intestinal microbiome compositions (4 studies) in MS. These results indicated that probiotics may have beneficial effects on the prevention and treatment of multiple sclerosis.