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Hydrogel is a type of versatile platform with various biomedical applications after rational structure and functional design that leverages on material engineering to modulate its physicochemical properties (e.g., stiffness, pore size, viscoelasticity, microarchitecture, degradability, ligand presentation, stimulus-responsive properties, etc.) and influence cell signaling cascades and fate. In the past few decades, a plethora of pioneering studies have been implemented to explore the cell–hydrogel matrix interactions and figure out the underlying mechanisms, paving the way to the lab-to-clinic translation of hydrogel-based therapies. In this review, we first introduced the physicochemical properties of hydrogels and their fabrication approaches concisely. Subsequently, the comprehensive description and deep discussion were elucidated, wherein the influences of different hydrogels properties on cell behaviors and cellular signaling events were highlighted. These behaviors or events included integrin clustering, focal adhesion (FA) complex accumulation and activation, cytoskeleton rearrangement, protein cyto-nuclei shuttling and activation (e.g., Yes-associated protein (YAP), catenin, etc.), cellular compartment reorganization, gene expression, and further cell biology modulation (e.g., spreading, migration, proliferation, lineage commitment, etc.). Based on them, current in vitro and in vivo hydrogel applications that mainly covered diseases models, various cell delivery protocols for tissue regeneration and disease therapy, smart drug carrier, bioimaging, biosensor, and conductive wearable/implantable biodevices, etc. were further summarized and discussed. More significantly, the clinical translation potential and trials of hydrogels were presented, accompanied with which the remaining challenges and future perspectives in this field were emphasized. Collectively, the comprehensive and deep insights in this review will shed light on the design principles of new biomedical hydrogels to understand and modulate cellular processes, which are available for providing significant indications for future hydrogel design and serving for a broad range of biomedical applications.

Lung cancer (LCa), the most frequent malignancy worldwide, causes millions of mortalities each year. Overexpression of the long noncoding RNA MIR210HG in LCa has been established; however, a more comprehensive investigation into its biological role within LCa is imperative. This study aimed to validate the MIR210H levels in LCa tissues and cells. The expression of indicated genes was evaluated using quantitative real‐time polymerase chain reaction (qRT‐PCR) and/or Western blotting. The viability, proliferation, migration, and invasion of LCa cells were measured using the 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT), colony formation, wound healing, and transwell assays, respectively. The methylation levels of LCa cells were determined via methylation‐specific PCR; additionally, chromatin immunoprecipitation or RNA immunoprecipitation assays were performed to determine the targeting relationship between DNA methyltransferase 1 (DNMT1) and the SH3‐domain containing CRB2 like 3 (SH3GL3) promoters and the interaction between DNMT1 and MIR210HG, respectively. Our findings revealed the upregulation of MIR210HG, coupled with a diminished expression of SH3GL3 in LCa tissues and cells. Knockdown of MIR210HG or overexpression of SH3GL3 suppressed the proliferative, migratory, and invasive capacities of the cells. DNMT1 bound to the SH3GL3 promoter region, and MIR210HG inhibited the transcription of SH3GL3 by recruiting DNMT1. These findings indicate that MIR210HG facilitates LCa cell growth and metastasis by repressing SH3GL3 transcription via the recruitment of DNMT1 to the SH3GL3 promoter region.

It is widely known that the skeletal structure of clusters reflects the number of skeletal bonding electron pairs involved, which is called the polyhedral skeletal electron pair theory (PSEPT) or Wade and Mingos rules. While recent computational studies propose that the increase of skeletal electrons of polyhedral clusters leads to the flat structure beyond the PSEPT, little experimental evidence has been demonstrated. Herein, we report the synthesis of a C 2 B 4 R 4 carborane 2 featuring a flat ribbon-like structure. The C 2 B 4 core of 2 bearing 16 skeletal electrons in the singlet-ground state defies both the [4 n  + 2] Hückel’s rule and Baird’s rule. Nevertheless, the delocalization of those electrons simultaneously induces two independent π- and two independent σ-aromatic ring currents, rendering quadruple aromaticity. The polyhedral skeletal electron pair theory (PESPT), also known as Wade-Mingos’ rules, defines a relationship between skeletal bonding electron pairs and structure of clusters. Here the authors report the synthesis, structure and computational studies of planar C 2 B 4 R 4 carboranes that do not adhere to PESPT.

From 2004 onwards, the Chinese government has freely offered complimentary Chinese herbal medicine (CHM) to Chinese HIV/AIDS patients, alongside the prescribed first line therapy of highly active antiretroviral therapy (HAART). Thus, we aimed to explore the effectiveness and safety of CHM for patients with HIV/AIDS. The data from the Guangxi pilot database and antiviral treatment sites database have been respectively developed into two datasets in this prospective cohort real-world study, the CHM combined HAART group (the integrated group) and the HAART group. A 1:1 propensity score matching (PSM) was performed and the longitudinal data were analyzed using a generalized estimating equation (GEE) model with an autocorrelation matrix and log link function attached to the Gamma distribution. A final sample of 629 patients, 455 and 174 in the integrated group and HAART group respectively, were obtained from the full dataset. As covariates for PSM, gender, age, baseline CD4+ and CD4+/ CD8+ were assessed based on the results of the logistic regression analyses. Following PSM, 166 pairs from the full dataset were matched successfully, with 98 pairs in the baseline CD4+ > 200 subgroup, and 55 pairs in the baseline CD4+ ≤ 200 subgroup. In the full dataset, HAART group achieved higher CD4+ count (OR = 1.119, 95%CI [1.018, 1.230]) and CD4+/CD8+ ratio (OR = 1.168, 95%CI [1.045, 1.305]) than the integrated group, so did in the CD4+ > 200 subgroup. For the CD4+ ≤ 200 subgroup, the CD4+ (OR = 0.825, 95%CI [0.694, 0.980]) and CD4+/CD8+ (OR = 0.826, 95%CI [0.684, 0.997]) of the integrated group were higher than those of the HAART group. The safety outcomes showed that there were no significant differences in BUN, ALT and AST levels between the groups but Cr showed significantly higher levels in HAART groups of all three datasets. Compared to HAART alone, CHMs combined with HAART had better effects in improving the immune function of HIV/AIDS in patients with baseline CD4+ count ≤ 200. The results of the two subgroups are in opposite directions, and chance does not explain the apparent subgroup effect. A study with larger sample size and longer follow-up period is warranted in order to increase study credibility.

Heme Oxygen-1 (HO-1)-modified bone marrow mesenchymal stem cells (BMMSCs) are effective to protect and repair transplanted small bowel and intestinal epithelial cells (IECs); however, the mechanism and the role of HO-1/BMMSCs-derived exosomes is unclear. In the present study, we aimed to verify that exosomes from a HO-1/BMMSCs and IEC-6 cells (IEC-6s) co-culture system could reduce the apoptosis of IEC-6s and decrease the expression of the tight junction protein, zona occludens 1, in the inflammatory environment. Using mass spectrometry, we revealed that high mobility group box 3 (HMGB3) and phosphorylated c-Jun NH2-terminal kinase (JNK), under the influence of differentially abundant proteins identified through proteomic analysis, play critical roles in the mechanism. Further studies indicated that microRNA miR-200b, which was upregulated in exosomes derived from the co-culture of HO-1/BMMSCs and IEC-6s, exerted its role by targeting the 3′ untranslated region of Hmgb3 in this biological process. Functional experiments confirmed that miR-200b overexpression could reduce the inflammatory injury of IEC-6s, while intracellular miR-200b knockdown could significantly block the protective effect of HO-1/BMMSCs exosomes on the inflammatory injury of IEC-6s. In addition, the level of miR-200b in cells and exosomes derived from HO-1/BMMSCs stimulated by tumor necrosis factor alpha was significantly upregulated. In a rat small bowel transplantation model of allograft rejection treated with HO-1/BMMSCs, we confirmed that the level of miR-200b in the transplanted small bowel tissue was increased significantly, while the level of HMGB3/JNK was downregulated significantly. In conclusion, we identified that exosomes derived from HO-1/BMMSCs play an important role in alleviating the inflammatory injury of IECs. The mechanism is related to miR-200b targeting the abnormally increased expression of the Hmgb3 gene in IECs induced by inflammatory injury. The reduced level of HMGB3 then decreases the inflammatory injury.

Recently, we revealed that TAPBPR is a peptide exchange catalyst that is important for optimal peptide selection by MHC class I molecules. Here, we asked whether any other co-factors associate with TAPBPR, which would explain its effect on peptide selection. We identify an interaction between TAPBPR and UDP-glucose:glycoprotein glucosyltransferase 1 (UGT1), a folding sensor in the calnexin/calreticulin quality control cycle that is known to regenerate the Glc1Man9GlcNAc2 moiety on glycoproteins. Our results suggest the formation of a multimeric complex, dependent on a conserved cysteine at position 94 in TAPBPR, in which TAPBPR promotes the association of UGT1 with peptide-receptive MHC class I molecules. We reveal that the interaction between TAPBPR and UGT1 facilities the reglucosylation of the glycan on MHC class I molecules, promoting their recognition by calreticulin. Our results suggest that in addition to being a peptide editor, TAPBPR improves peptide optimisation by promoting peptide-receptive MHC class I molecules to associate with the peptide-loading complex.

Conventional soft-lithography methods involving the transfer of molecular \"inks\" from polymeric stamps to substrates often encounter micrometer-scale resolution limits due to diffusion of the transferred molecules during printing. We report a \"subtractive\" stamping process in which silicone rubber stamps, activated by oxygen plasma, selectively remove hydroxyl-terminated alkanethiols from self-assembled monolayers (SAMs) on gold surfaces with high pattern fidelity. The covalent interactions formed at the stamp-substrate interface are sufficiently strong to remove not only alkanethiol molecules but also gold atoms from the substrate. A variety of high-resolution patterned features were fabricated, and stamps were cleaned and reused many times without feature deterioration. The remaining SAM acted as a resist for etching exposed gold features. Monolayer backfilling into the lift-off areas enabled patterned protein capture, and 40-nanometer chemical patterns were achieved.

Annealing‐induced embrittlement has long been considered unavoidable in metallic glasses because it annihilates free volume (i.e., locally loosely‐packed regions, LLPRs) required for plasticity. Here, we overturn this paradigm by demonstrating that sub‐Tg annealing simultaneously increases both the strength and compressive plasticity of a chemically tailored Zr‐based metallic glass, with plastic strain increasing by >150%. Our experimental analyses reveal that strategically employed Ni─Cu repulsion drives elemental partitioning during annealing, which seeds nanoscale chemical heterogeneity. Concurrently, atomistic simulations suggest the emergence of locally densely‐packed regions (LDPRs) with characteristically low activation energy for shear transformation. These findings indicate that plasticity can be sustained by heterogeneous structures wherein densely‐packed motifs, alongside conventional loosely‐packed regions, serve as potential shear transformation sites. This shifts the design paradigm from merely introducing LLPRs to strategically engineering heterogeneous structures that enable compensatory plasticity. This work challenges the dogma that annealing inevitably embrittles metallic glasses. We demonstrate that sub‐Tg annealing, guided by positive mixing enthalpy and constrained kinetics, can drive a self‐organized compositional fluctuation that creates an interface‐free heterogeneous structure. Within this structure, deformable densely‐packed regions (LDPRs) arise to compensate for the vanishing loose‐packed regions (LLPRs), enabling a simultaneous increase in strength and ductility exceeding 150% through compensatory plasticity.

Objective Age-related hearing loss (ARHL) is largely attributed to dysfunction of the cochlear stria vascularis (SV). This study aimed to define the molecular mechanisms underlying SV aging and identify therapeutic targets. Methods Lifespan transcriptomic profiling and systems-level analyses were performed on mouse cochleae to reveal age-associated pathways. Functional and pharmacological assays were used to examine the effects of IκB kinase (IKK) inhibition both in vitro and in aging mice. Results Aged SV displayed profound transcriptional reprogramming toward a pro-inflammatory and metabolically impaired state. A regulatory hub comprising AP-1, NF-κB, and CEBPB was identified as a master inflammatory switch. TNFα activation disrupted the blood-labyrinth barrier and mitochondrial function, while IKK inhibition reversed these effects and mitigated hearing loss in aging mice. Conclusions Targeting the IKK–NF-κB axis preserves cochlear integrity and offers a promising therapeutic strategy to prevent age-related hearing loss.

OsmiR535 belongs to the miR156/miR529/miR535 superfamily, a highly conserved miRNA family in plants. OsmiR535 is involved in regulating the cold-stress response, modulating plant development, and determining panicle architecture and grain length. However, the role that OsmiR535 plays in plant responses to drought and salinity are elusive. In the current study, molecular and genetic engineering techniques were used to elucidate the possible role of OsmiR535 in response to NaCl, PEG(Poly ethylene glycol), ABA(Abscisic acid), and dehydration stresses. Our results showed that OsmiR535 is induced under stressed conditions as compared to control. With transgenic and CRISPR/Cas9 knockout system techniques, our results verified that either inhibition or knockout of OsmiR535 in rice could enhance the tolerance of plants to NaCl, ABA, dehydration and PEG stresses. In addition, the overexpression of OsmiR535 significantly reduced the survival rate of rice seedlings during PEG and dehydration post-stress recovery. Our results demonstrated that OsmiR535 negatively regulates the stress response in rice. Moreover, our practical application of CRISPR/Cas9 mediated genome editing created a homozygous 5 bp deletion in the coding sequence of OsmiR535, demonstrating that OsmiR535 could be a useful genetic editing target for drought and salinity tolerance and a new marker for molecular breeding of Oryza sativa.