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One of the main challenges for immune checkpoint blockade antibodies lies in malignancies with limited T-cell responses or immunologically “cold” tumors. Inspired by the capability of fever-like heat in inducing an immune-favorable tumor microenvironment, mild photothermal therapy (PTT) is proposed to sensitize tumors to immune checkpoint inhibition and turn “cold” tumors “hot.” Here we present a combined all-in-one and all-in-control strategy to realize a local symbiotic mild photothermal-assisted immunotherapy (SMPAI). We load both a near-infrared (NIR) photothermal agent IR820 and a programmed death-ligand 1 antibody (aPD-L1) into a lipid gel depot with a favorable property of thermally reversible gel-to-sol phase transition. Manually controlled NIR irradiation regulates the release of aPD-L1 and, more importantly, increases the recruitment of tumor-infiltrating lymphocytes and boosts T-cell activity against tumors. In vivo antitumor studies on 4T1 and B16F10 models demonstrate that SMPAI is an effective and promising strategy for treating “cold” tumors. Mild photothermal therapy can be used to induce a favourable immunological response. In this study, the authors combine a photothermal therapy sensitizer and anti-PD-L1 into a lipid gel and find that, on controlled delivery to tumours, it potentiates anti-PD therapy and boosts anticancer efficacy.

Chronic endometritis (CE) is a persistent inflammatory disorder of the endometrium, associated with infertility, recurrent pregnancy loss, and implantation failure. Diagnosis primarily depends on hysteroscopy and immunohistochemistry, while microbial dysbiosis and antibiotic resistance pose significant challenges to effective management. The pathogenesis of CE involves microbial infections that induce immune dysregulation through TLR/NLR signaling pathways, metabolic reprogramming of immune cells, miRNA-mediated inflammatory responses, and DNA methylation alterations. The activation of pro-inflammatory mediators and the NLRP3 inflammasome further aggravates endometrial dysfunction. Treatment typically includes oral antibiotics and intrauterine therapies, although their efficacy is variable. Probiotics have demonstrated potential in restoring microbial balance. This review outlines the inflammatory mechanisms underlying CE and recent therapeutic advancements, highlighting potential targets for improving treatment outcomes.

Objects with different shapes, materials and temperatures can emit distinct polarizations and spectral information in mid-infrared band, which provides a unique signature in the transparent window for object identification. However, the crosstalk among various polarization and wavelength channels prevents from accurate mid-infrared detections at high signal-to-noise ratio. Here, we report full-polarization metasurfaces to break the inherent eigen-polarization constraint over the wavelengths in mid-infrared. This recipe enables to select arbitrary orthogonal polarization basis at individual wavelength independently, therefore alleviating the crosstalk and efficiency degradation. A six-channel all-silicon metasurface is specifically presented to project focused mid-infrared light to distinct positions at three wavelengths, each with a pair of arbitrarily chosen orthogonal polarizations. An isolation ratio of 117 between neighboring polarization channels is experimentally recorded, exhibiting detection sensitivity one order of magnitude higher than existing infrared detectors. Remarkably, the high aspect ratio ~30 of our meta-structures manufactured by deep silicon etching technology at temperature −150 °C guarantees the large and precise phase dispersion control over a broadband from 3 to 4.5 μm. We believe our results would benefit the noise-immune mid-infrared detections in remote sensing and space-to-ground communications. Dispersive eigen-polarization engineering enabled polychromatic full-polarization control in mid-infrared.

Background Ischemia/reperfusion injury (I/RI) impedes the progress of flap and allograft transplantation. Among various strategies to address oxidative stress (OS) and mitochondrial dysfunction associated with I/RI, exosomes derived from adipose-derived stem cells (ADSCs) subjected to hypoxia pretreatment show significant therapeutic potential. Methods and results This study assessed the effects of ADSC-derived exosomes (ADSC-Ex) from normoxic and hypoxic conditions on reactive oxygen species (ROS), mitochondrial calcium ion (Ca 2+ ) influx, mitochondrial potential, and cell apoptosis in an ischemia/reperfusion (I/R) model. Mass spectrometry (MS) was utilized to analyze differentially expressed proteins in hypoxic ADSC-Ex compared to normoxic controls. The functions of significantly upregulated proteins were investigated through knockdown experiments in hypoxic ADSC-Ex on alleviating I/R injury (I/RI) in HUVECs. Hypoxic ADSC-Ex significantly mitigated I/RI in vascular endothelial cells both in vitro and in vivo. This effect was associated with reduced ROS and mitochondrial Ca 2+ influx, and protection of mitochondrial potential. MS identified several proteins that were significantly upregulated in hypoxic ADSC-Ex, with Vesicle-associated membrane protein 4 (VAMP4) emerging as a pivotal molecule involved in alleviating I/RI in vascular endothelial cells. Conclusion This study demonstrated that hypoxic ADSC-Ex reduced ROS and mitochondrial dysfunction in vascular endothelial cells through VAMP4, thereby attenuating I/RI. This finding might provide a new approach for treating post-transplant I/RI.

Background A keloid is a fibroproliferative disorder occurring in wounds characterized by an exaggerated response to injury. To date, no effective cure has been identified. As multipotent stem cells, human adipose-derived stem cells (ADSCs) may show the possibility for curing diseases such as fibrosis. This study sought to explore the potential role of human ADSCs in curing keloids. Methods After culture in conditioned medium, gene and protein expression of keloid fibroblasts was examined using real-time polymerase chain reaction (RT-PCR) and Western blotting, while analysis of the cell cycle was used to measure the proliferative properties of the cells. Furthermore, ex vivo explant cultures were used to test the effects of ADSC-conditioned medium (ADSC-CM) on CD31 + and CD34 + expression in keloid tissue. Results Our experimental results show that ADSC-CM was able to attenuate extracellular matrix-related gene expression as well as decrease protein expression. Cell proliferation was significantly suppressed in our study. CD31 + and CD34 + vessels in ex vivo explants were reduced by 55% and 57% in treatment groups compared with control groups. Conclusions Human ADSC-CM significantly inhibited keloid fibroblast-related bioactivities.

Ferroptosis has emerged as a promising strategy for cancer treatment. Nevertheless, the efficiency of ferroptosis-mediated therapy remains a challenge due to high glutathione (GSH) levels and insufficient endogenous hydrogen peroxide in the tumor microenvironment. Herein, we presented a nitric-oxide (NO) boost-GSH depletion strategy for enhanced ferroptosis therapy through a multifunctional nanoplatform with near-infrared (NIR) triggered NO release. The nanoplatform, IS@ATF, was designed that self-assembled by loading the NO donor L-arginine (L-Arg), ferroptosis inducer sorafenib (SRF), and indocyanine green (ICG) onto tannic acid (TA)-Fe 3+ ‒metal-phenolic networks (MPNs) modified with hydroxyethyl starch. Inside the tumor, SRF could inhibit GSH biosynthesis, impair the activation of glutathione peroxidase 4, and disrupt the ferroptosis defensive system. In conjunction with TA-Fe 3+ ‒MPNs, which has cascaded Fenton catalytic activity, it could navigate the lethal ferroptosis to cancer cells. Upon NIR laser irradiation, the ICG-generated ROS oxidated L-Arg to a substantial quantity of NO, which further depleted the intracellular GSH and caused LPO accumulation, enhancing cell ferroptosis. Moreover, ICG also serves as a photothermal agent that can produce hyperthermia when exposed to irradiation, further potentiating ferroptosis therapy. In addition, the nanoplatform showed significantly improved tumor therapeutic efficacy and anti-metastasis efficiency. This work thus demonstrated that utilizing NO boost-GSH depletion to enhance ferroptosis induction is a feasible and promising strategy for cancer treatment. Graphical abstract

Titanium alloys are critically important materials, yet their development has long been constrained by a fundamental trade-off between yield strength and uniform elongation—a more challenging limitation than the conventional strength–ductility trade-off. Here, we present a dual strategy for α–β titanium alloys that transforms high oxygen from an embrittling liability into a powerful performance enabler. First, we leverage high oxygen ( ≥0.40%) to activate prominent pyramidal < c  +  a > slip in the α-phase. Second, we engineer a tailored α–β microstructure through alloy design (Ti–O–Fe), laser-based powder bed fusion, and annealing to enable sustained slip transfer across α–β interfaces. The resulting high-strength α–β alloys achieve record uniform elongations: Ti-0.45O-4Fe delivers ≥14% (total: ≥27%) at yield strengths ≥980 MPa, and Ti-0.5O-5Fe achieves ≥13% (total: ≥23%) at yield strengths ≥1075 MPa. This work simultaneously addresses the yield strength–uniform elongation trade-off and oxygen embrittlement, demonstrating a design paradigm for α–β titanium alloys. This work transforms oxygen from an embrittling contaminant into a key asset in titanium alloys, simultaneously overcoming the strength-ductility trade-off and oxygen embrittlement.

Ferroptosis is a recently-defined tumor suppression mechanism, but the sensitivity of many tumorigenic cells to ferroptosis is limited by their deficient expression of acyl-CoA synthetase long-chain family member 4 (ACSL4). Here, we report the discovery of a photosensitizer, namely TPCI, which can evoke ACSL4-independent ferroptosis of cancer cells in photodynamic therapy. Through co-localization with 12-lipoxygenase (ALOX12) in multiple subcellular organelles, TPCI activates ALOX12 to generate lipid reactive oxygen species in large quantity and trigger cell ferroptosis. Intriguingly, confining TPCI exclusively in lysosomes switches the cell death from ferroptosis to apoptosis. More strikingly, the ferroptosis mediated by TPCI-induced ALOX12 activation does not require the participation of ACSL4. Therefore, our study identifies TPCI as the first ALOX12 activator to induce ferroptosis independent of ACSL4, which renders a viable therapeutic approach on the basis of distinct ferroptosis of cancer cells, regardless their ACSL4 expressions.

Dear Editor, The in vitro propagation （IVP） of animal spermatogonial stem cells （SSCs） provides materials for studying the mechanism of spermatogenesis and for developing novel animal transgenesis and human therapy. The IVP of SSCs is reported to be promoted by exogenous growth factors, among which the glial cell-derived neurotrophic factor （GDNF） has been recognized as the single essential one [1, 2]. FGF2,

This study assessed the impact of the cervical microbiome on reproductive outcomes in frozen embryo transfer (FET) patients. This cross-sectional study included 120 women (aged 20-40 years) undergoing FET. A cervical sample obtained before embryo transfer was analyzed using 16S full-length assembly sequencing technology (16S-FAST), which detects full length 16S rDNA. We found that >48% of the identified species were novel. The cervical microbiome was clustered into three cervical microbiome types (CMT): CMT1, dominated by ; CMT2, dominated by ; and CMT3, dominated by other bacteria. CMT1 had a significantly higher biochemical pregnancy rate ( =0.008) and clinical pregnancy rate ( =0.006) than CMT2 and CMT3. Logistic analysis showed that compared to CMT1, CMT2 and CMT3 were independent risk factors for biochemical pregnancy failure (odds ratio [OR]: 6.315, 95% confidence interval [CI]: 2.047-19.476, =0.001; OR: 3.635, 95% CI: 1.084-12.189, =0.037) and clinical pregnancy failure (OR: 4.883, 95% CI: 1.847-12.908, =0.001; OR: 3.478, 95% CI: 1.221-9.911, =0.020). A -dominated group as a diagnostic indicator of biochemical and clinical pregnancy positive had area under the curve (AUC) values of 0.651( =0.008) and 0.645( =0.007), respectively. Combining the cervical microbiome with embryonic stage optimized the diagnostic performance for biochemical and clinical pregnancy failure with AUC values of 0.743( <0.001) and 0.702( <0.001), respectively. Additionally, relative abundance of predicted biochemical pregnancy positive with AUC values of 0.679( =0.002) and clinical pregnancy positive with AUC values of 0.659( =0.003). Cervical microbiome profiling using 16S-FAST enables stratification of the chance of becoming pregnant prior to FET. Knowledge of the cervical microbiota may enable couples to make more balanced decisions regarding the timing and continuation of FET treatment cycles.