Renewable Electroconductive Hydrogels for Accelerated Diabetic Wound Healing and Motion Monitoring.

Diabetic foot ulcers (DFUs), a prevalent complication of diabetes mellitus, may result in an amputation. Natural and renewable hydrogels are desirable materials for DFU dressings due to their outstanding biosafety and degradability. However, most hydrogels are usually only used for wound repair and cannot be employed to monitor motion because of their inherent poor mechanical properties and electrical conductivity. Given that proper wound stretching is beneficial for wound healing, the development of natural hydrogel patches integrated with wound repair properties and motion monitoring was expected to achieve efficient and accurate wound healing. Here, we designed a dual-network (chitosan and sodium alginate) hydrogel embedded with lignin-Ag and quercetin-melanin nanoparticles to achieve efficient wound healing and motion monitoring. The double network formed by the covalent bond and electrostatic interaction confers the hydrogel with superior mechanical properties. Instead of the usual chemical reagents, genipin extracted from Gardenia was used as a cross-linking agent for the hydrogel and consequently improved its biosafety. Furthermore, the incorporation of lignin-Ag nanoparticles greatly enhanced the mechanical strength, antibacterial efficacy, and conductivity of the hydrogel. The electrical conductivity of hydrogels gives them the capability of motion monitoring. The motion sensing mechanism is that stretching of the hydrogel induced by motion changes the conductivity of the hydrogel, thus converting the motion into an electrical signal. Meanwhile, quercetin-melanin nanoparticles confer exceptional adhesion, antioxidant, and anti-inflammatory properties to the hydrogels. The system ultimately achieved excellent wound repair and motion monitoring performance and was expected to be used for stretch-assisted safe and accurate wound repair in the future.

Revisiting the Ultraviolet Absorption Cross Section of Gaseous Nitrous Acid (HONO): New Insights for Atmospheric HONO Budget.

Nitrous acid (HONO) is an important source of hydroxyl radicals (OH) in the atmosphere. Precise determination of the absolute ultraviolet (UV) absorption cross section of gaseous HONO lays the basis for the accurate measurement of its concentration by optical methods and the estimation of HONO loss rate through photolysis. In this study, we performed a series of laboratory and field intercomparison experiments for HONO measurement between striping coil-liquid waveguide capillary cell (SC-LWCC) photometry and incoherent broadband cavity-enhanced absorption spectroscopy (IBBCEAS). Specified HONO concentrations prepared by an ultrapure standard HONO source were utilized for laboratory intercomparisons. Results show a consistent ∼22% negative bias in measurements of the IBBCEAS compared with a SC-LWCC photometer. It is confirmed that the discrepancies occurring between these techniques are associated with the overestimation of the absolute UV absorption cross sections through careful analysis of possible uncertainties. We quantified the absorption cross section of gaseous HONO (360-390 nm) utilizing a custom-built IBBCEAS instrument, and the results were found to be 22-34% lower than the previously published absorption cross sections widely used in HONO concentration retrieval and atmospheric chemical transport models (CTMs). This suggests that the HONO concentrations retrieved by optical methods based on absolute absorption cross sections may have been underestimated by over 20%. Plus, the daytime loss rate and unidentified sources of HONO may also have evidently been overestimated in pre-existing studies. In summary, our findings underscore the significance of revisiting the absolute absorption cross section of HONO and the re-evaluation of the previously reported HONO budgets.

Characteristics and sources of peroxyacetyl nitrate (PAN) in the rural North China Plain: Results from 1-year continuous observations.

Peroxyacetyl nitrate (PAN) is an important photochemical pollutant in the troposphere, whereas long-term measurements are scarce in rural areas in North China Plain (NCP), resulting in unclear seasonal variations and sources of PAN in rural NCP. In this study, we conducted a 1-year observation of PAN during 2021-2022 at the rural NCP site. The average concentrations of PAN were 1.10, 0.75, 0.65, and 0.88 ppbv in spring, summer, autumn, and winter, respectively, with a 1-year average of 0.81 ± 0.60 ppbv. Calculations indicate that the loss of PAN through thermal decomposition in summer accounts for 43.2% of the total formed PAN, which is an important reason for the low concentration of PAN in summer. We speculate that since the correlation between PAN and O3 in winter is significantly lower than that in other seasons, the observed regional transport of PAN cannot be ignored in winter. Through budget analysis, regional transport accounted for 12.8% and 55.9% of the observed PAN on the spring and winter pollution days, respectively, which showed that regional transport played key roles during the photochemical pollution of the rural NCP in winter. The potential source contribution function revealed that the transported PAN mainly comes from southern Hebei in spring. In winter, the transported PAN was mainly from Langfang, Hengshui, and southern Beijing. Our findings may aid in understanding PAN variations in different seasons in rural areas and highlight the impact of regional transport on the PAN budget.

Dimethyl Bisphenolate Ameliorates Carbon Tetrachloride-Induced Liver Injury by Regulating Oxidative Stress-Related Genes.

Liver disease accounts for millions of deaths per year all over the world due to complications from cirrhosis and liver injury. In this study, a novel compound, dimethyl bisphenolate (DMB), was synthesized to investigate its role in ameliorating carbon tetrachloride (CCl4)-induced liver injury through the regulation of oxidative stress-related genes. The structure of DMB was confirmed based on its hydrogen spectrum and mass spectrometry. DMB significantly reduced the high levels of ALT, AST, DBIL, TBIL, ALP, and LDH in a dose-dependent manner in the sera of CCl4-treated rats. The protective effects of DMB on biochemical indicators were similar to those of silymarin. The ROS fluorescence intensity increased in CCl4-treated cells but significantly weakened in DMB-treated cells compared with the controls. DMB significantly increased the content of oxidative stress-related GSH, Nrf2, and GCLC dose-dependently but reduced MDA levels in CCl4-treated cells or the liver tissues of CCl4-treated rats. Moreover, DMB treatment decreased the expression levels of P53 and Bax but increased those of Bcl2. In summary, DMB demonstrated protective effects on CCl4-induced liver injury by regulating oxidative stress-related genes.

Both indirect maternal and direct fetal genetic effects reflect the observational relationship between higher birth weight and lower adult bone mass.

BACKGROUND: Birth weight is considered not only to undermine future growth, but also to induce lifelong diseases; the aim of this study is to explore the relationship between birth weight and adult bone mass. METHODS: We performed multivariable regression analyses to assess the association of birth weight with bone parameters measured by dual-energy X-ray absorptiometry (DXA) and by quantitative ultrasound (QUS), independently. We also implemented a systemic Mendelian randomization (MR) analysis to explore the causal association between them with both fetal-specific and maternal-specific instrumental variables. RESULTS: In the observational analyses, we found that higher birth weight could increase the adult bone area (lumbar spine, ß-coefficient= 0.17, P < 2.00 × 10-16; lateral spine, ß-coefficient = 0.02, P = 0.04), decrease bone mineral content-adjusted bone area (BMCadjArea) (lumbar spine, ß-coefficient= - 0.01, P = 2.27 × 10-14; lateral spine, ß-coefficient = - 0.05, P = 0.001), and decrease adult bone mineral density (BMD) (lumbar spine, ß-coefficient = - 0.04, P = 0.007; lateral spine; ß-coefficient = - 0.03, P = 0.02; heel, ß-coefficient = - 0.06, P < 2.00 × 10-16), and we observed that the effect of birth weight on bone size was larger than that on BMC. In MR analyses, the higher fetal-specific genetically determined birth weight was identified to be associated with higher bone area (lumbar spine; ß-coefficient = 0.15, P = 1.26 × 10-6, total hip, ß-coefficient = 0.15, P = 0.005; intertrochanteric area, ß-coefficient = 0.13, P = 0.0009; trochanter area, ß-coefficient = 0.11, P = 0.03) but lower BMD (lumbar spine, ß-coefficient = - 0.10, P = 0.01; lateral spine, ß-coefficient = - 0.12, P = 0.0003, and heel ß-coefficient = - 0.11, P = 3.33 × 10-13). In addition, we found that the higher maternal-specific genetically determined offspring birth weight was associated with lower offspring adult heel BMD (ß-coefficient = - 0.001, P = 0.04). CONCLUSIONS: The observational analyses suggested that higher birth weight was associated with the increased adult bone area but decreased BMD. By leveraging the genetic instrumental variables with maternal- and fetal-specific effects on birth weight, the observed relationship could be reflected by both the direct fetal and indirect maternal genetic effects.

GeO2-doped ring-core photonic crystal fiber for supporting robust orbital angular momentum modes.

Orbital angular momentum (OAM)-mode-supported photonic crystal fibers (PCFs) have inspired intensive research in modern fiber optics due to the robust propagation and theoretically unlimited signal-carried channels. In this paper, a dual-cladding GeO2-doped ring-core PCF is designed, and a strategy for optimizing OAM mode properties is analyzed by structure parameters and GeO2-doping concentration. Numeric results show that high structural degrees of freedom are available to improve the effective refractive index separation (within the vector modes), chromatic dispersion, effective mode field area, nonlinear coefficient, and OAM mode purity in terms of inner cladding, outer cladding, and ring-core. In particular, the effective refractive index separation and chromatic dispersion can exhibit a high order magnitude of 10-3 and a low value in the broad band from 1.3 µm to 1.7 µm, respectively. In addition to structural optimization, doping high index material into the ring-core is another way to regulate the fiber performance by controlling the doping concentration. A systematic investigation shows that as the doping concentration increases, the effective refractive index separation and mode purity increase obviously, while the dispersion and mode field area gradually decrease. This flexible manipulation offers a method for customizing the optical properties of OAM-supported PCFs in communication and sensor systems.

Higher Mean Arterial Pressure during Cardiopulmonary Bypass May Not Prevent Acute Kidney Injury in Elderly Patients Undergoing Cardiac Surgery.

We aimed to evaluate the role of higher mean arterial pressure (MAP) during cardiopulmonary bypass (CPB) in preventing development of acute kidney injury (AKI). Methods. We evaluated a population of elderly individuals >60 years of age undergoing CPB to find correlation of MAP during CPB with development of AKI after the surgery. Patients who experienced sustained low MAP during the CPB defined as that of <65 mmHg were compared with those that had sustained high MAP of >65 mmHg for their outcome with regard to AKI. The KDIGO criteria were used to define presence of acute kidney injury. Results. Of the total 92 patients, 50 were in the low-pressure group and 42 were in the high-pressure group. The MAP was 61.14 ± 5.54 mmHg in the low-pressure group and 68.97 ± 3.65 mmHg in the high-pressure group (p < 0.001). 13 (26%) in the low-pressure group and 17 (40.48%) in the high-pressure group developed AKI (p = 0.140). Male sex was associated with an increased incidence of cardiac surgery-associated AKI (p = 0.034). Conclusions. A higher MAP in the range of 65-75 mmHg during the cardiopulmonary bypass does not significantly prevent acute kidney injury in elderly patients undergoing cardiac valve surgery.

Systemic evaluation of the relationship between psoriasis, psoriatic arthritis and osteoporosis: observational and Mendelian randomisation study.

OBJECTIVES AND METHODS: With 432 513 samples from UK Biobank dataset, multivariable linear/logistic regression were used to estimate the relationship between psoriasis/psoriatic arthritis (PsA) and estimated bone mineral density (eBMD)/osteoporosis, controlling for potential confounders. Here, confounders were set in three ways: model0 (including age, height, weight, smoking and drinking), model1 (model0 +regular physical activity) and model2 (model1 +medication treatments). The eBMD was derived from heel ultrasound measurement. And 4904 patients with psoriasis and 847 patients with PsA were included in final analysis. Mendelian randomisation (MR) approach was used to evaluate the causal effect between them. RESULTS: Lower eBMD were observed in patients with PsA than in controls in both model0 (ß-coefficient=-0.014, p=0.0006) and model1 (ß-coefficient=-0.013, p=0.002); however, the association disappeared when conditioning on treatment with methotrexate or ciclosporin (model2) (ß-coefficient=-0.005, p=0.28), mediation analysis showed that 63% of the intermediary effect on eBMD was mediated by medication treatment (p<2E-16). Patients with psoriasis without arthritis showed no difference of eBMD compared with controls. Similarly, the significance of higher risk of osteopenia in patients with PsA (OR=1.27, p=0.002 in model0) could be eliminated by conditioning on medication treatment (p=0.244 in model2). Psoriasis without arthritis was not related to osteopenia and osteoporosis. The weighted Genetic Risk Score analysis found that genetically determined psoriasis/PsA were not associated with eBMD (p=0.24 and p=0.88). Finally, MR analysis showed that psoriasis/PsA had no causal effect on eBMD, osteoporosis and fracture. CONCLUSIONS: The effect of PsA on osteoporosis was secondary (eg, medication) but not causal. Under this hypothesis, psoriasis without arthritis was not a risk factor for osteoporosis.

Identification and characterization of a novel L-type lectin (MjLTL2) from kuruma shrimp (Marsupenaeus japonicus).

L-type lectins (LTLs) belong to the lectin family and are characterized by a conserved structural motif in their carbohydrate recognition domain. LTLs are homologous to leguminous lectins. In this study, we identified and functionally characterized an LTL from kuruma shrimp Marsupenaeus japonicus. We designated this LTL as MjLTL2. MjLTL2 contains a signal peptide, a Lectin_leg domain, a coiled coil, and transmembrane domain. MjLTL2 is distributed in hemocytes, heart, hepatopancreas, gill, stomach, and intestine; higher expression levels are seen in hemocytes and the hepatopancreas than in other tissues. MjLTL2 was upregulated following challenge of shrimp with Vibrio anguillarum and white spot syndrome virus (WSSV). MjLTL2 can agglutinate several bacteria without Ca2+. In addition, MjLTL2 could bind to several Gram-positive and -negative bacteria by binding to their lipopolysaccharide and peptidoglycan. However, MjLTL2 could not enhance the clearance of V. anguillarum in vivo. In the presence of WSSV infection, MjLTL2 knockdown by RNA interference resulted in a 7-day lower cumulative mortality of M. japonicus. Moreover, less VP19, VP24, VP26, and VP28 mRNAs were extracted from the hemocytes of MjLTL2 knockdown shrimp than from the control. These results suggest that MjLTL2 is involved in immune responses in shrimp.

Resveratrol induces cervical cancer HeLa cell apoptosis through the activation and nuclear translocation promotion of FOXO3a.

Resveratrol (trans-3,4'V,5-trihydroxystilbene) presents antioxidant, anti-inflammatory, and cardioprotective functions in addition to its anticancer potential. In this study, we explored how resveratrol, as an anticancer agent, effectively influences cervical cancer HeLa cells. Our data showed that resveratrol could significantly inhibit HeLa cell proliferation and induce their apoptosis, as measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay and flow cytometry. The immunofluorescence staining results in the present study suggested that resveratrol could facilitate FOXO3a nuclear translocation. We then focused on the mechanism of resveratrol in promoting HeLa cell apoptosis. The following experiments suggested that the possible initial mechanism involves the upregulation Forkhead box O (FOXO) 3a expression, which further increases the expression of Bcl-2 interacting mediator of cell death (BIM), the gene transcribed in apoptosis. Resveratrol could also inactivate the basal extracellular signal-regulated kinase (ERK) activity, causing FOXO3a activation and resulting in HeLa cell apoptosis. In summary, both mechanisms stimulated the accumulation of activated FOXO3a, promoted its nuclear translocation, and ultimately caused HeLa cell apoptosis. Thus, resveratrol may have a potential in the treatment of cervical cancer.

Identification and functional characterization of unfolded protein response transcription factor ATF6 gene in kuruma shrimp Marsupenaeus japonicus.

Activating transcription factor 6 (ATF6) pathway is the key branch of unfolded protein response (UPR). In this study, a homolog of ATFα from Marsupenaeus japonicus (MjATF6) was identified using genome sequencing and characterized, so as to investigate the role of ATF6 pathway in anti-viral immunity of M. japonicus. The cDNA of MjATF6 obtained was 1008 bp in length, with an open reading frame (ORF) of 849bp, which had encoded a putative of 283 amino acid proteins. Results of qRT-PCR showed that MjATF6 was distributed in all the six tested tissues, with the higher expression level being seen in hemocytes and hepatopancreas. Furthermore, MjATF6 expression would be up-regulated from 1 day to 7 day under white spot syndrome virus (WSSV) challenge. In comparison, RNA interference-induced MjATF6 knockdown had resulted in a lower 7-day cumulative mortality of M. japonicus in the presence of WSSV infection. Additionally, our results also revealed that less VP28 mRNA was extracted from hemocytes or hepatopancreas of MjATF6 knockdown shrimp than that from the control. Taken together, these results have confirmed that ATF6 pathway is vital for WSSV replication, and that UPR in M. japonicus may facilitate WSSV infection.

Effect of dexmedetomidine on postoperative delirium in elderly patients undergoing hip fracture surgery.

Dexmedetomidine is a highly selective central α2 adrenergic receptor agonist, which has anti sympathetic, sedative and analgesic effects. The aim of this study was to investigate the effect of dexmedetomidine on postoperative delirium in elderly patients undergoing hip fracture surgery. The results showed that the dosage of sufentanil and propofol decreased significantly in the experimental group (P<0.05). The price-henry pain scores of 10min, 1H and 6h in the experimental group were significantly reduced after the operation. At the same time, there were 3 cases (4.28%) of postoperative delirium in the experimental group, which were significantly less than 12 cases (17.14%) in the control group. The dosage of propofol in the operation is a risk factor for postoperative delirium. Dexmedetomidin can significantly reduce the amount of propofol in the operation and it has a neuroprotective effect, which can reduce the incidence of postoperative delirium in the elderly. In the elderly patients with hip surgery, its adjuvant to general anesthesia can effectively reduce narcotic drug dosage and reduce the incidence of postoperative delirium.

High glucose concentration induces endothelial cell proliferation by regulating cyclin-D2-related miR-98.

Cyclin D2 is involved in the pathology of vascular complications of type 2 diabetes mellitus (T2DM). This study investigated the role of cyclin-D2-regulated miRNAs in endothelial cell proliferation of T2DM. Results showed that higher glucose concentration (4.5 g/l) significantly promoted the proliferation of rat aortic endothelial cells (RAOECs), and significantly increased the expression of cyclin D2 and phosphorylation of retinoblastoma 1 (p-RB1) in RAOECs compared with those under low glucose concentration. The cyclin D2-3' untranslated region is targeted by miR-98, as demonstrated by miRNA analysis software. Western blot also confirmed that cyclin D2 and p-RB1 expression was regulated by miR-98. The results indicated that miR-98 treatment can induce RAOEC apoptosis. The suppression of RAOEC growth by miR-98 might be related to regulation of Bcl-2, Bax and Caspase 9 expression. Furthermore, the expression levels of miR-98 decreased in 4.5 g/l glucose-treated cells compared with those treated by low glucose concentration. Similarly, the expression of miR-98 significantly decreased in aortas of established streptozotocin (STZ)-induced diabetic rat model compared with that in control rats; but cyclin D2 and p-RB1 levels remarkably increased in aortas of STZ-induced diabetic rats compared with those in healthy control rats. In conclusion, this study demonstrated that high glucose concentration induces cyclin D2 up-regulation and miR-98 down-regulation in the RAOECs. By regulating cyclin D2, miR-98 can inhibit human endothelial cell growth, thereby providing novel therapeutic targets for vascular complication of T2DM.

Sulindac has strong antifibrotic effects by suppressing STAT3-related miR-21.

Pulmonary fibrosis (PF) is a disease with an unknown cause and a poor prognosis. In this study, we aimed to explore the pathogenesis of PF and the mechanism of sulindac in attenuating bleomycin (BLM)-induced PF. The rat PF model was induced by BLM and verified through histological studies and hydroxyproline assay. The severity of BLM-induced PF in rats and other effects, such as the extent of the wet lung to bw ratios, thickening of alveolar interval or collagen deposition, was obviously ameliorated in sulindac-treated rat lungs compared with BLM-induced lungs. Sulindac also reversed the epithelial mesenchymal transition (EMT) and inhibited the PF process by restoring the levels of E-cadherin and α-smooth muscle actin (SMA) in A549 cells. Our results further demonstrated that the above effects of sulindac might be related to regulating of interferon gamma (IFN-γ) expression, which further affects signal transducers and activators of transcription 3 (STAT3) and phosphorylated STAT3 (p-STAT3) levels. Moreover, higher miR-21 levels with the decreased E-cadherin and increased α-SMA expressions were found in transforming growth factor-ß1-treated A549 cells, which can be reversed by sulindac. Collectively, our results demonstrate that by decreasing IFN-γ-induced STAT3/p-STAT3 expression to down-regulate miR-21, sulindac could significantly reverse EMT in A549 cells and prevent BLM-induced PF.

Insights into the tolerant function of VWA proteins in terms of expression analysis and RGLG5-VWA crystal structure.

The VWA domain commonly functions as a crucial component of multiprotein complexes, facilitating protein-protein interactions. However, limited studies have focused on the systemic study of VWA proteins in plants. Here, we identified 28 VWA protein genes in Arabidopsis thaliana, categorized into three clades, with one tandem duplication event and four paralogous genes within collinearity blocks. Then, we determined their expression patterns under abiotic stresses by transcriptomic analysis. All five RGLG genes were found to be responsive to at least one kind of abiotic stress, and RGLG5 was identified as a multiple stress-responsive gene, coding an E3 ubiquitin ligase with a VWA domain and a C-terminal RING domain. Subsequently, we explored tolerant function of RGLG5 by determining the crystal structure of its VWA domain. The structural comparison revealed the allosteric regulation mechanism of RGLG5-VWA, wherein the deflection of α7 led to displacement of key residue binding metal ion within MIDAS motif. Our findings provide full-scale knowledge on VWA proteins, and insights into tolerant function of RGLG5-VWA in terms of crystal structure.

The regulation of RGLG2-VWA by Ca2+ ions.

RGLG2, an E3 ubiquitin ligase in Arabidopsis thaliana, affects hormone signaling and participates in drought regulation. Here, we determined two crystal structures of RGLG2 VWA domain, representing two conformations, open and closed, respectively. The two structures reveal that Ca2+ ions are allosteric regulators of RGLG2-VWA, which adopts open state when NCBS1(Novel Calcium ions Binding Site 1) binds Ca2+ ions and switches to closed state after Ca2+ ions are removed. This mechanism of allosteric regulation is identical to RGLG1-VWA, but distinct from integrin α and ß VWA domains. Therefore, our data provide a backdrop for understanding the role of the Ca2+ ions in conformational change of VWA domain. In addition, we found that RGLG2closed, corresponding to low affinity, can bind pseudo-ligand, which has never been observed in other VWA domains.

Danshensu methyl ester attenuated LPS-induced acute lung injury by inhibiting TLR4/NF-κB pathway.

Acute Lung Injury (ALI) manifests as an acute exacerbation of pulmonary inflammation with high mortality. The potential application of Danshensu methyl ester (DME, synthesized in our lab) in ameliorating ALI has not been elucidated. Our results demonstrated that DME led to a remarkable reduction in lung injury. DME promoted a marked increase in antioxidant enzymes, like superoxide dismutase (SOD), and glutathione (GSH), accompanied by a substantial decrease in reactive oxygen species (ROS), myeloperoxidase (MPO), and malondialdehyde (MDA). Moreover, DME decreased the production of IL-1ß, TNF-α and IL-6, in vitro and in vivo. TLR4 and MyD88 expression is reduced in the DME-treated cells or tissues, which further leading to a decrease of p-p65 and p-IκBα. Meanwhile, DME effectively facilitated an elevation in cytoplasmic p65 expression. In summary, DME could ameliorate ALI by its antioxidant functionality and anti-inflammation effects through TLR4/NF-κB, which implied that DME may be a viable medicine for lung injury.

Advancements in Stimulus-Responsive Co-Delivery Nanocarriers for Enhanced Cancer Immunotherapy.

Cancer immunotherapy has emerged as a novel therapeutic approach against tumors, with immune checkpoint inhibitors (ICIs) making significant clinical practice. The traditional ICIs, PD-1 and PD-L1, augment the cytotoxic function of T cells through the inhibition of tumor immune evasion pathways, ultimately leading to the initiation of an antitumor immune response. However, the clinical implementation of ICIs encounters obstacles stemming from the existence of an immunosuppressive tumor microenvironment and inadequate infiltration of CD8+T cells. Considerable attention has been directed towards advancing immunogenic cell death (ICD) as a potential solution to counteract tumor cell infiltration and the immunosuppressive tumor microenvironment. This approach holds promise in transforming "cold" tumors into "hot" tumors that exhibit responsiveness to antitumor. By combining ICD with ICIs, a synergistic immune response against tumors can be achieved. However, the combination of ICD inducers and PD-1/PD-L1 inhibitors is hindered by issues such as poor targeting and uncontrolled drug release. An advantageous solution presented by stimulus-responsive nanocarrier is integrating the physicochemical properties of ICD inducers and PD-1/PD-L1 inhibitors, facilitating precise delivery to specific tissues for optimal combination therapy. Moreover, these nanocarriers leverage the distinct features of the tumor microenvironment to accomplish controlled drug release and regulate the kinetics of drug delivery. This article aims to investigate the advancement of stimulus-responsive co-delivery nanocarriers utilizing ICD and PD-1/PD-L1 inhibitors. Special focus is dedicated to exploring the advantages and recent advancements of this system in enabling the combination of ICIs and ICD inducers. The molecular mechanisms of ICD and ICIs are concisely summarized. In conclusion, we examine the potential research prospects and challenges that could greatly enhance immunotherapeutic approaches for cancer treatment.

Calcium Carbonate/Polydopamine Composite Nanoplatform Based on TGF-ß Blockade for Comfortable Cancer Immunotherapy.

Cancer pain seriously reduces the quality of life of cancer patients. However, most research about cancer focuses solely on inhibiting tumor growth, neglecting the issue of cancer pain. Therefore, the development of therapeutic agents with both tumor suppression and cancer pain relief is crucial to achieve human-centered treatment. Here, the work reports curcumin (CUR) and ropivacaine (Ropi) coincorporating CaCO3/PDA nanoparticles (CaPNMCUR+Ropi) that realized efficient tumor immunotherapy and cancer pain suppression. The therapeutic efficiency and mechanism are revealed in vitro and in vivo. The results indicate that CaPNMCUR+Ropi underwent tumor microenvironment-responsive degradation and realized rapid release of calcium ions, Ropi, and CUR. The excessive intracellular calcium triggered the apoptosis of tumor cells, and the transient pain caused by the tumor injection was relieved by Ropi. Simultaneously, CUR reduced the levels of immunosuppressive factor (TGF-ß) and inflammatory factor (IL-6, IL-1ß, and TNF-α) in the tumor microenvironment, thereby continuously augmenting the immune response and alleviating inflammatory pain of cancer animals. Meanwhile, the decrease of TGF-ß leads to the reduction of transient receptor potential vanilloid 1 (TRPV1) expression, thereby alleviating hyperalgesia and achieving long-lasting analgesic effects. The design of the nanosystem provides a novel idea for human-centered tumor treatment in the future.