Organic mechanophores have been widely adopted for polymer mechanotransduction. However, most examples of polymer mechanotransduction inevitably experience macromolecular chain rupture, and few of them mimic mussel’s mechanochemical regeneration, a mechanically mediated process from functional units to functional materials in a controlled manner. In this paper, inorganic mechanoluminescent (ML) materials composed of CaZnOS-ZnS-SrZnOS: Mn²⁺ were used as a mechanotransducer since it features both piezoelectricity and mechanolunimescence. The utilization of ML materials in polymerization enables both mechanochemically controlled radical polymerization and the synthesis of ML polymer composites. This procedure features a mechanochemically controlled manner for the design and synthesis of diverse mechanoresponsive polymer composites.

Photocatalytic reduction of CO₂ into fuels provides a prospective tactic for regulating the global carbon balance utilizing renewable solar energy. However, CO₂ molecules are difficult to activate and reduce due to the thermodynamic stability and chemical inertness. In this work, we develop a novel strategy to promote the adsorption and activation of CO₂ molecules via the rapid energy exchange between the photoinduced Br vacancies and CO₂ molecules. Combining in situ continuous wave-electron paramagnetic resonance (cw-EPR) and pulsed EPR technologies, we observe that the spin–spin relaxation time (T₂) of BiOBr is decreased by 198 ns during the CO₂ photoreduction reaction, which is further confirmed by the broadened EPR linewidth. This result reveals that there is an energy exchange interaction between in situ formed Br vacancies and CO₂ molecules, which promotes the formation of high-energy CO₂ molecules to facilitate the subsequent reduction reaction. In addition, theoretical calculations indicate that the bended CO₂ adsorption configuration on the surface of BiOBr with Br vacancies caused the decrease of the lowest unoccupied molecular orbital of the CO₂ molecule, which makes it easier for CO₂ molecules to acquire electrons and get activated. In situ diffuse reflectance infrared Fourier transform spectroscopy further shows that the activated CO₂ molecules are favorably converted to key intermediates of COOH*, resulting in a CO generation rate of 9.1 μmol g⁻¹ h⁻¹ and a selectivity of 100%. This study elucidates the underlying mechanism of CO₂ activation at active sites and deepens the understanding of CO₂ photoreduction reaction.

The emergence of antibiotic tolerance, characterized by the prolonged survival of bacteria following antibiotic exposure, in natural bacterial populations, especially in pathogens carrying antibiotic resistance genes, has been an increasing threat to public health. However, the major causes contributing to the formation of antibiotic tolerance and underlying molecular mechanisms are yet poorly understood. Herein, we show that potassium sorbate (PS), a widely used food additive, triggers a high level of fluoroquinolone tolerance in bacteria carrying mobile colistin resistance gene mcr. Mechanistic studies demonstrate that PS treatment results in the accumulation of intracellular fumarate, which activates bacterial two-component system and decreases the expression level of outer membrane protein OmpF, thereby reducing the uptake of ciprofloxacin. In addition, the supplementation of PS inhibits aerobic respiration, reduces reactive oxygen species production and alleviates DNA damage caused by bactericidal antibiotics. Furthermore, we demonstrate that succinate, an intermediate product of the tricarboxylic acid cycle, overcomes PS-mediated ciprofloxacin tolerance. In multiple animal models, ciprofloxacin treatment displays failure outcomes in PS preadministrated animals, including comparable survival and bacterial loads with the vehicle group. Taken together, our works offer novel mechanistic insights into the development of antibiotic tolerance and uncover potential risks associated with PS use.

Despite substantial progress in the treatment of castration-resistant prostate cancer (CRPC), including radiation therapy and immunotherapy alone or in combination, the response to treatment remains poor due to the hypoxic and immunosuppressive nature of the tumor microenvironment. Herein, we exploited the bioreactivity of novel polymer–lipid manganese dioxide nanoparticles (PLMDs) to remodel the tumor immune microenvironment (TIME) by increasing the local oxygen levels and extracellular pH and enhancing radiation-induced immunogenic cell death. This study demonstrated that PLMD treatment sensitized hypoxic human and murine CRPC cells to radiation, significantly increasing radiation-induced DNA double-strand breaks and ultimately cell death, which enhanced the secretion of damage-associated molecular patterns, attributable to the induction of autophagy and endoplasmic reticulum stress. Reoxygenation via PLMDs also polarized hypoxic murine RAW264.7 macrophages toward the M1 phenotype, enhancing tumor necrosis factor alpha release, and thus reducing the viability of murine CRPC TRAMP-C2 cells. In a syngeneic TRAMP-C2 tumor model, intravenous injection of PLMDs suppressed, while radiation alone enhanced recruitment of regulatory T cells and myeloid-derived suppressor cells. Pretreatment with PLMDs followed by radiation down-regulated programmed death-ligand 1 and promoted the infiltration of antitumor CD8⁺ T cells and M1 macrophages to tumor sites. Taken together, TIME modulation by PLMDs plus radiation profoundly delayed tumor growth and prolonged median survival compared with radiation alone. These results suggest that PLMDs plus radiation is a promising treatment modality for improving therapeutic efficacy in radioresistant and immunosuppressive solid tumors.

Improving droplet velocity as much as possible is considered as the key to improving both printing speed and printing distance of the piezoelectric drop-on-demand inkjet printing technology. There are 3 tough and contradictory issues that need to be addressed simultaneously, namely, the actuation pressure of the piezoelectric printhead, satellite droplets, and the air resistance, which seems almost impossible to achieve with classical methods. Herein, a novel solution is introduced. By modulating the positive crosstalk effect inside and outside the printhead, self-tuning can be achieved, including self-reinforcing of the actuation pressure, self-restraining of satellite droplets, and self-weakening of the air resistance, thereby greatly improving droplet velocity. Based on these mechanisms, waveform design methods for different inks and printheads are investigated. The results demonstrate that monodisperse droplet jetting with a maximum velocity of 27.53 m/s can be achieved, reaching 3 to 5 times that of the classical method (5 to 8 m/s). Correspondingly, the printing speed and distance can be simultaneously increased by almost 10 times, demonstrating an ability of direct printing on irregular surface. Meanwhile, the compatibility of ink materials is expanded, as the Ohnesorge number and the viscosity of printable inks for the printhead used are increased from 0.36–0.72 to 0.03–1.18 and from 10–12 cp to 1–40.3 cp, respectively, even breaking the traditional limitations of the piezoelectric printing technology (Ohnesorge number of 0.1 to 1; viscosity of 1 to 25 cp). All the above provide a new perspective for improving droplet velocity and may even offer a game-changing choice for expanding the boundaries of the piezoelectric drop-on-demand inkjet printing technology.

While genetic factors were associated with over 30% of colorectal cancer (CRC) patients, mutations in CRC-susceptibility genes were identified in only 5% to 10% of these patients. Besides, previous studies on hereditary CRC were largely designed to analyze germline mutations in patients with single genetic high-risk factor, which limited understanding of the association between genotype and phenotypes. From January 2015 to December 2018, we retrospectively enrolled 2,181 patients from 8,270 consecutive CRC cases, covering 5 categories of genetic high-risk factors. Leukocyte genomic DNA was analyzed for germline mutations in cancer predisposition genes. The germline mutations under each category were detected and analyzed in association with CRC susceptibility, clinical phenotypes, and prognoses. A total of 462 pathogenic variants were detected in 19.3% of enrolled CRC patients. Mismatch repair gene mutation was identified in 9.1% of patients, most prevalent across all high-risk groups. Homologous recombination (HR) gene mutations were detected in 6.5% of cases, penetrated in early-onset and extra-colonic cancer risk groups. Mutations in HR genes, including BARD1, RAD50, and ATM, were found to increase CRC risk with odds ratios of 2.8-, 3.1-, and 3.1-fold, respectively. CRC patients with distinct germline mutations manifested heterogeneous phenotypes in clinicopathology and long-term prognoses. Thus, germline mutation screenings should be performed for CRC patients with any of those genetic risk factors. This study also reveals that HR gene mutations may be another major driver for increased CRC risk.

Near-infrared (NIR) transparent optical filters show great promise in night vision and receiving windows. However, NIR optical filters are generally prepared by laborious, environmentally unfriendly processes that involve metal oxides or petroleum-based polymers. We propose a lignin capturing–fusing approach to manufacturing optical biofilters based on molecular collaboration between lignin and cellulose from waste agricultural biomass. In this process, lignin is captured via self-assembly in a cellulose network; then, the lignin is fused to fill gaps and hold the cellulose fibers tightly. The resulting optical biofilter featured a dense structure and smooth surface with NIR transmittance of ~90%, ultralow haze of close to 0%, strong ultraviolet-visible light blocking (~100% at 400 nm and 57.58% to 98.59% at 550 nm). Further, the optical biofilter has comprehensive stability, including water stability, solvent stability, thermal stability, and environmental stability. Because of its unique properties, the optical biofilter demonstrates potential applications in the NIR region, such as an NIR-transmitting window, NIR night vision, and privacy protection. These applications represent a promising route to produce NIR transparent optical filters starting from lignocellulose biomass waste.

Prostate cancer (PCa) is a common malignant tumor with high morbidity and mortality worldwide. The prostate cancer stem cell (PCSC) model provides novel insights into the pathogenesis of PCa and its therapeutic response. However, the roles and molecular mechanisms of specific genes in mediating fate decisions of PCSCs and carcinogenesis of PCa remain to be elusive. In this study, we have explored the expression, function, and mechanism of AZGP1P2, a pseudogene of AZGP1, in regulating the stemness and apoptosis of PCSCs and treatment resistance of docetaxel in castration-resistant prostate cancer (CRPC). We revealed that AZGP1P2 was downregulated in CRPC cell lines and PCSCs, while it was positively associated with progression-free interval. Upregulation of the AZGP1P2 enhanced the sensitivity of docetaxel treatment in CRPCs via inhibiting their stemness. RNA pull-down associated with mass spectrometry analysis, co-immunoprecipitation assay, and RNA immunoprecipitation assay demonstrated that AZGP1P2 could bind to UBA1 and RBM15 as a “writer” of methyltransferase to form a compound. UBA1, an E1 ubiquitin-activating enzyme, contributed to RBM15 protein degradation via ubiquitination modification. Methylated RNA immunoprecipitation assay displayed that RBM15 controlled the mRNA decay of TPM1 in m6A methylation. Furthermore, a xenograft mouse model and patient-derived organoids showed that the therapeutic effect of docetaxel in CRPC was increased by AZGP1P2 in vivo. Collectively, these results imply that AZGP1P2 mediates the stemness and apoptosis of PCSCs and promotes docetaxel therapeutic effect by suppressing tumor growth and metastasis via UBA1/RBM15-mediated TPM1 mRNA decay in CRPC.

Gene transcription often occurs in discrete bursts, and it can be difficult to deduce the underlying regulatory mechanisms for transcriptional bursting with limited experimental data. Here, we categorize numerous states of single eukaryotic genes and identify 6 essential transcriptional events, each comprising a series of state transitions; transcriptional bursting is characterized as a sequence of 4 events, capable of being organized in various configurations, in addition to the beginning and ending events. By associating transcriptional kinetics with mean durations and recurrence probabilities of the events, we unravel how transcriptional bursting is modulated by various regulators including transcription factors. Through analytical derivation and numerical simulation, this study reveals key state transitions contributing to transcriptional sensitivity and specificity, typical characteristics of burst profiles, global constraints on intrinsic transcriptional noise, major regulatory modes in individual genes and across the genome, and requirements for fast gene induction upon stimulation. It is illustrated how biochemical reactions on different time scales are modulated to separately shape the durations and ordering of the events. Our results suggest that transcriptional patterns are essentially controlled by a shared set of transcriptional events occurring under specific promoter architectures and regulatory modes, the number of which is actually limited.

The limitations of autologous bone grafts necessitate the development of advanced biomimetic biomaterials for efficient cranial defect restoration. The cranial bones are typical flat bones with sandwich structures, consisting of a diploe in the middle region and 2 outer compact tables. In this study, we originally developed 2 types of flat-bone-mimetic β-tricalcium phosphate bioceramic scaffolds (Gyr-Comp and Gyr-Tub) by high-precision vat-photopolymerization-based 3-dimensional printing. Both scaffolds had 2 outer layers and an inner layer with gyroid pores mimicking the diploe structure. The outer layers of Gyr-Comp scaffolds simulated the low porosity of outer tables, while those of Gyr-Tub scaffolds mimicked the tubular pore structure in the tables of flat bones. The Gyr-Comp and Gyr-Tub scaffolds possessed higher compressive strength and noticeably promoted in vitro cell proliferation, osteogenic differentiation, and angiogenic activities compared with conventional scaffolds with cross-hatch structures. After implantation into rabbit cranial defects for 12 weeks, Gyr-Tub achieved the best repairing effects by accelerating the generation of bone tissues and blood vessels. This work provides an advanced strategy to prepare biomimetic biomaterials that fit the structural and functional needs of efficacious bone regeneration.