Helicobacter pylori infection is characterized as progressive processes of bacterial persistence and chronic gastritis with features of infiltration of mononuclear cells more than granulocytes in gastric mucosa. Angiopoietin-like 4 (ANGPTL4) is considered a double-edged sword in inflammation-associated diseases, but its function and clinical relevance in H. pylori-associated pathology are unknown. Here, we demonstrate both pro-colonization and pro-inflammation roles of ANGPTL4 in H. pylori infection. Increased ANGPTL4 in the infected gastric mucosa was produced from gastric epithelial cells (GECs) synergistically induced by H. pylori and IL-17A in a cagA-dependent manner. Human gastric ANGPTL4 correlated with H. pylori colonization and the severity of gastritis, and mouse ANGPTL4 from non-bone marrow-derived cells promoted bacteria colonization and inflammation. Importantly, H. pylori colonization and inflammation were attenuated in Il17a^−/−, Angptl4^−/−, and Il17a^−/−Angptl4^−/− mice. Mechanistically, ANGPTL4 bound to integrin αV (ITGAV) on GECs to suppress CXCL1 production by inhibiting ERK, leading to decreased gastric influx of neutrophils, thereby promoting H. pylori colonization; ANGPTL4 also bound to ITGAV on monocytes to promote CCL5 production by activating PI3K–AKT–NF-κB, resulting in increased gastric influx of regulatory CD4⁺ T cells (T_regs) via CCL5–CCR4-dependent migration. In turn, ANGPTL4 induced T_reg proliferation by binding to ITGAV to activate PI3K–AKT–NF-κB, promoting H. pylori-associated gastritis. Overall, we propose a model in which ANGPTL4 collectively ensures H. pylori persistence and promotes gastritis. Efforts to inhibit ANGPTL4-associated pathway may prove valuable strategies in treating H. pylori infection.

Amino acid bioconjugation technology has emerged as a pivotal tool for linking small-molecule fragments with proteins, antibodies, and even cells. The study in Nature by Chang and Toste introduces a redox-based strategy for tryptophan bioconjugation, employing N-sulfonyloxaziridines as oxidative cyclization reagents, demonstrating high efficiency comparable to traditional click reactions. Meanwhile, this tool provides feasible methods for investigating the mechanisms underlying functional tryptophan-related biochemical processes, paving the way for protein function exploration, activity-based proteomics for functional amino acid identification and characterization, and even the design of covalent inhibitors.

Molecular materials possessing switchable magneto-optical properties are of great interest due to their potential applications in spintronics and molecular devices. However, switching their photoluminescence (PL) and single-molecule magnet (SMM) behavior via light-induced structural changes still constitutes a formidable challenge. Here, a series of cubane structures were synthesized via self-assembly of 9-anthracene carboxylic acid (HAC) and rare-earth ions. All complexes exhibited obvious photochromic phenomena and complete PL quenching upon Xe lamp irradiation, which were realized via the synergistic effect of photogenerated radicals and [4 + 4] photocycloaddition of the AC components. The quenched PL showed the largest fluorescence intensity change (99.72%) in electron-transfer photochromic materials. A reversible decoloration process was realized via mechanical grinding, which is unexpectedly in the electron-transfer photochromic materials. Importantly, an SMM behavior of the Dy analog was observed after room-temperature irradiation due to the photocycloaddition of AC ligands and the photogenerated stable radicals changed the electrostatic ligand field and magnetic coupling. Moreover, based on the remarkably photochromic and photoluminescent properties of these compounds, 2 demos were applied to support their application in information anti-counterfeiting and inkless printing. This work, for the first time utilizing the simultaneous modulation of photocycloaddition and photogenerated radicals in one system, realizes complete PL quenching and light-induced SMM behavior, providing a dynamical switch for the construction of multifunctional polymorphic materials with optical response and optical storage devices.

The combination of all-inorganic perovskites (PVSKs) and polymers allows for free-standing flexible optoelectronic devices. However, solubility difference of the PVSK precursors and concerns over the compatibility between polymer carriers and PVSKs imply a great challenge to incorporate different kinds of PVSKs into polymer matrices by the same manufacturing process. In this work, PVSK precursors are introduced into poly(2-hydroxyethyl acrylate) (PHEA) hydrogels in sequence, in which the PVSK-gel composites are achieved with full-color emissions by simply varying the precursor species. Moreover, it is found that CsBr has a higher interaction energy with the (111) plane of CsPbBr₃ than the (110) plane; thus, the CsPbBr₃ crystals with a shape of truncated cube and tetragon are observed during the CsPbBr₃–Cs₄PbBr₆ phase transition over time. The PVSK-gel composites feature excellent bendability, elasticity, and stretchable deformation (tensile strain > 500%), which allows for 3D printing emissive customized stereoscopic architectures with shape-memory features.

Although cytochrome P450 enzymes are the most versatile biocatalysts in nature, there is insufficient comprehension of the molecular mechanism underlying their functional innovation process. Here, by combining ancestral sequence reconstruction, reverse mutation assay, and progressive forward accumulation, we identified 5 founder residues in the catalytic pocket of flavone 6-hydroxylase (F6H) and proposed a “3-point fixation” model to elucidate the functional innovation mechanisms of P450s in nature. According to this design principle of catalytic pocket, we further developed a de novo diffusion model (P450Diffusion) to generate artificial P450s. Ultimately, among the 17 non-natural P450s we generated, 10 designs exhibited significant F6H activity and 6 exhibited a 1.3- to 3.5-fold increase in catalytic capacity compared to the natural CYP706X1. This work not only explores the design principle of catalytic pockets of P450s, but also provides an insight into the artificial design of P450 enzymes with desired functions.

Engineered microstructures that mimic in vivo tissues have demonstrated great potential for applications in regenerative medicine, drug screening, and cell behavior exploration. However, current methods for engineering microstructures that mimic the multi-extracellular matrix and multicellular features of natural tissues to realize tissue-mimicking microstructures in vitro remain insufficient. Here, we propose a versatile method for constructing tissue-mimicking heterogeneous microstructures by orderly integration of macroscopic hydrogel exchange, microscopic cell manipulation, and encapsulation modulation. First, various cell-laden hydrogel droplets are manipulated at the millimeter scale using electrowetting on dielectric to achieve efficient hydrogel exchange. Second, the cells are manipulated at the micrometer scale using dielectrophoresis to adjust their density and arrangement within the hydrogel droplets. Third, the photopolymerization of these hydrogel droplets is triggered in designated regions by dynamically modulating the shape and position of the excitation ultraviolet beam. Thus, heterogeneous microstructures with different extracellular matrix geometries and components were constructed, including specific cell densities and patterns. The resulting heterogeneous microstructure supported long-term culture of hepatocytes and fibroblasts with high cell viability (over 90%). Moreover, the density and distribution of the 2 cell types had significant effects on the cell proliferation and urea secretion. We propose that our method can lead to the construction of additional biomimetic heterogeneous microstructures with unprecedented potential for use in future tissue engineering applications.

Ulcerative colitis (UC) is often accompanied by intestinal inflammation and disruption of intestinal epithelial structures, which are closely associated with changes in the intestinal microbiota. We previously revealed that Min pigs, a native Chinese breed, are more resistant to dextran sulfate sodium (DSS)-induced colitis than commercial Yorkshire pigs. Characterizing the microbiota in Min pigs would allow identification of the core microbes that confer colitis resistance. By analyzing the microbiota linked to the disease course in Min and Yorkshire pigs, we observed that Bacillus spp. were enriched in Min pigs and positively correlated with pathogen resistance. Using targeted screening, we identified and validated Bacillus siamensis MZ16 from Min pigs as a bacterial species with biofilm formation ability, superior salt and pH tolerance, and antimicrobial characteristics. Subsequently, we administered B. siamensis MZ16 to conventional or microbiota-deficient BALB/c mice with DSS-induced colitis to assess its efficacy in alleviating colitis. B. siamensis MZ16 partially counteracted DSS-induced colitis in conventional mice, but it did not mitigate DSS-induced colitis in microbiota-deficient mice. Further analysis revealed that B. siamensis MZ16 administration improved intestinal ecology and integrity and immunological barrier function in mice. Compared to the DSS-treated mice, mice preadministered B. siamensis MZ16 exhibited improved relative abundance of potentially beneficial microbes (Lactobacillus, Bacillus, Christensenellaceae R7, Ruminococcus, Clostridium, and Eubacterium), reduced relative abundance of pathogenic microbes (Escherichia-Shigella), and maintained colonic OCLN and ZO-1 levels and IgA and SIgA levels. Furthermore, B. siamensis MZ16 reduced proinflammatory cytokine levels by reversing NF-κB and MAPK pathway activation in the DSS group. Overall, B. siamensis MZ16 from Min pigs had beneficial effects on a colitis mouse model by enhancing intestinal barrier functions and reducing inflammation in a gut microbiota-dependent manner.

Typically developing (TD) individuals can readily orient attention according to others’ eye-gaze direction, an ability known as social attention, which involves both innate and acquired components. To distinguish between these two components, we used a critical flicker fusion technique to render gaze cues invisible to participants, thereby largely reducing influences from consciously acquired strategies. Results revealed that both visible and invisible gaze cues could trigger attentional orienting in TD adults (aged 20 to 30 years) and children (aged 6 to 12 years). Intriguingly, only the ability to involuntarily respond to invisible gaze cues was negatively correlated with autistic traits among all TD participants. This ability was substantially impaired in adults with autism spectrum disorder (ASD) and in children with high autistic traits. No such association or reduction was observed with visible gaze cues. These findings provide compelling evidence for the functional demarcation of conscious and unconscious gaze-triggered attentional orienting that emerges early in life and develops into adulthood, shedding new light on the differentiation of the innate and acquired aspects of social attention. Moreover, they contribute to a comprehensive understanding of social endophenotypes of ASD.

The prevalence of food allergies is increasing dramatically and causing serious public health concerns. Notably, melatonin metabolism imbalance in patients with food allergies; however, the role of melatonin in food allergies remains unclear. Here, we demonstrated that melatonin suppresses food allergy responses and reprograms the gut microbiota of food-allergic mice, while melatonin aggravates food allergy during gut microbiota depletion. Mechanistically, melatonin boosts the degranulation of mast cells by up-regulating the expression of membrane high-affinity immunoglobulin E (IgE) receptor (FcεRI). Melatonin increases the mRNA expression of Rabenosyn-5 (a component of factors for endosome recycling and Rab interactions) through melatonin receptor 2 (MT2)–extracellular signal-regulated kinase (ERK) signaling, thereby driving the recycling of FcεRI and elevating the abundance of membrane FcεRI. Likewise, the inhibition of MT2 attenuates melatonin-induced food allergy in mice with gut microbiota depletion. Collectively, our finding provides insights into the pathogenesis of food allergies and provides a potential therapeutic target for the prevention and treatment of food allergies.