Identifying and evaluating a disulfidptosis-related gene signature to predict prognosis in colorectal adenocarcinoma patients.

Disulfidptosis, a regulated form of cell death, has been recently reported in cancers characterized by high SLC7A11 expression, including invasive breast carcinoma, lung adenocarcinoma, and hepatocellular carcinoma. However, its role in colon adenocarcinoma (COAD) has been infrequently discussed. In this study, we developed and validated a prognostic model based on 20 disulfidptosis-related genes (DRGs) using LASSO and Cox regression analyses. The robustness and practicality of this model were assessed via a nomogram. Subsequent correlation and enrichment analysis revealed a relationship between the risk score, several critical cancer-related biological processes, immune cell infiltration, and the expression of oncogenes and cell senescence-related genes. POU4F1, a significant component of our model, might function as an oncogene due to its upregulation in COAD tumors and its positive correlation with oncogene expression. In vitro assays demonstrated that POU4F1 knockdown noticeably decreased cell proliferation and migration but increased cell senescence in COAD cells. We further investigated the regulatory role of the DRG in disulfidptosis by culturing cells in a glucose-deprived medium. In summary, our research revealed and confirmed a DRG-based risk prediction model for COAD patients and verified the role of POU4F1 in promoting cell proliferation, migration, and disulfidptosis.

Ultra-Fast-Charging, Long-Duration, and Wide-Temperature-Range Sodium Storage Enabled by Multiwalled Carbon Nanotube-Hybridized Biphasic Polyanion-Type Phosphate Cathode Materials.

Sodium-ion batteries (SIBs) represent a promising energy storage technology with great safety. Because of their high operating potential, superior structural stability, and prominent thermal stability, polyanion-type phosphates have garnered significant interest in superior prospective cathode materials for SIBs. Nevertheless, the disadvantages of poor intrinsic electronic conductivity, sluggish kinetics, and volume variation during sodiation/desodiation remain great challenges for satisfactory rate performance and cycle stability, which severely hinder their further practical applications. In this work, by adjusting the amounts of pretreated multiwalled carbon nanotubes (CNT) added intentionally at the beginning of the preparation, biphasic polyanion-type phosphate materials (marked as NFC) are synthesized through a one-pot solid state reaction methodology, which are composed of CNT-interwoven Na3V2(PO4)2F3 (NVPF) and a small amount of Na3V2(PO4)3 (NVP). Benefiting from the improved electronic conductivity and unique composition and structure, the optimized sample (labeled as NFC-2) illustrates exceptional cycle stability and remarkable rate performance. The discharge capacities of the NFC-2 electrode are 114.8 and 78.6 mAh g-1 tested at 20 and 5000 mA g-1, respectively. Notably, such an electrode still gives out 75.7% capacity retention upon 10 000 cycles at 5000 mA g-1. In situ X-ray diffraction analysis demonstrates that the NFC-2 cathode has outstanding structural reversibility during charge/discharge cycles. More importantly, such a biphasic material has achieved impressive electrochemical performance within a wide operating temperature range of -20-50 °C. When temperature is decreased to -20 °C, the NFC-2 electrode still delivers an initial discharge capacity of 102.4 mAh g-1 and exhibits a remarkable capacity retention of 97.8% even after 500 cycles at 50 mA g-1. In addition, the sodium-ion full cell assembled by integrating NFC-2 cathode and hard carbon anode shows a satisfying energy density of 431.3 Wh kg-1 at 20 mA g-1 with a better long-term cycle performance. The synergistic effect among high energy NVPF, conductive CNT, and stable NVP may lead to the great improvement in the electrochemical sodium storage performance of the NFC-2 sample. Such biphasic polyanion-type phosphate materials will inject new ideas into the material design for SIBs with excellent electrochemical performance and further promote practical applications of this advanced energy storage technology.

Metallophthalocyanine as ideal antibiotics without light: Mechanisms and applications.

The urgent global health problem of antimicrobial resistance (AMR) calls for the discovery of new antibiotics with innovative modes of action while considering the low toxicity to mammalian cells. This paper proposes a novel strategy for designing antibiotics with selective bacterial toxicity by exploiting the positional differences of electron transport chains (ETC) in bacterial and mammalian cells. The focus is on cytochrome c (cyt C) and its maturation system in E. coli. The catalytic oxidative activity of metallophthalocyanine (MPc), which have a distinctive M-N4 structure, is being investigated. Unlike previous applications based on light-activated reactive oxygen species (ROS) generation, this study exploits the ability of MPcs to oxidize Fe2+ to Fe3+ in cyt C and catalyze the formation of disulfide bonds between cysteine residues to interfere with cyt C maturation, disrupt the bacterial respiratory chain and selectively kills bacteria. In contrast, in mammalian cells, these MPcs are located in the lysosomes and cannot access the ETC in the mitochondria, thus achieving selective bacterial toxicity. Two MPcs that showed effective antibacterial activity in a wound infection model were identified. This study provides a valuable reference for the design of novel antibiotics based on M-N4-based metal complex molecules.

HBV infection effects prognosis and activates the immune response in intrahepatic cholangiocarcinoma.

BACKGROUND: The impact of HBV infection on the prognosis of patients with intrahepatic cholangiocarcinoma (ICC) remains uncertain, and the underlying mechanism has not been elucidated. This study aims to explore the potential mechanism via clinical perspectives and immune features. METHODS: We retrospectively reviewed 1308 patients with ICC treated surgically from January 2007 to January 2015. Then, we compared immune-related markers using immunohistochemistry staining to obtain the gene expression profile GSE107943 and related literature for preliminary bioinformatics analysis. Subsequently, we conducted a drug sensitivity assay to validate the role of TNFSF9 in the ICC organoid-autologous immune cell coculture system and in the patient-derived organoids-based xenograft platform. RESULTS: The analysis revealed that tumors in patients without HBV infection exhibited greater size and a higher likelihood of lymphatic metastasis, tumor invasion, and relapse. After resection, HBV-infected patients had longer survival time than uninfected patients (p<0.01). Interestingly, the expression of immune-related markers in HBV-positive patients with ICC was higher than that in uninfected patients (p<0.01). The percentage of CD8+ T cells in HBV-positive tissue was higher than that without HBV infection (p<0.05). We screened 21 differentially expressed genes and investigated the function of TNFSF9 through bioinformatics analyses. The expression of TNFSF9 in ICC organoids with HBV infection was lower than that in organoids without HBV infection. The growth of HBV-negative ICC organoids was significantly inhibited by inhibiting the expression of TNFSF9 with a neutralizing antibody. Additionally, the growth rate was faster in HbsAg (-) ICC patient-derived organoids-based xenograft model than in HbsAg (+) group. CONCLUSIONS: The activation of the immune response induced by HBV infection makes the prognosis of HBV-positive patients with ICC differ from that of uninfected patients.

Pd nanoparticles anchored Co-MOF for nitrophenol reduction.

Three nitrophenols are among the 126 priority toxic pollutants identified by the US Environmental Protection Agency. Catalyzing hydrogenation is a simple way to convert these toxic nitrophenols into harmless aminophenols. Commercial PdC has excellent catalytic hydrogenation activity but has weaknesses such as high price and low reusability. Here, we fabricated a series of nano-Pd 2D Co-MOF heterostructures and filtered for optimal Co-MOF@Pd0.0012, which contain ultra-low Pd content (0.08 wt%) and recorded high catalytic efficiency for 4-nitrophenol among the reported non-single atom catalyst due to edge and size effects. The TOF value of Co-MOF@Pd0.0012 is 9800 h-1, ∼206 times higher than that of PdC (Pd content, 10 wt%). Furthermore, Co-MOF@Pd0.0012 has been widely applied to catalyze the reduction of various nitrophenol substrates with higher than 99% conversion efficiency and selectivity.

Temperature-Dependent Biology and Population Performances of the Coffee Berry Borer Hypothenemus hampei (Ferrari) (Coleoptera: Curculionidae: Scolytinae) on Artificial Diet.

At different observation intervals of 1, 5, and 10 days during a trial period of 30 days, the mortality rates of Hypothenemus hampei were 100, 95, and 55%, and the fecundity rates were 0.55, 8.45, and 19.35 eggs/female, respectively. At temperatures of 18, 21, 24, and 27 °C, the development time of the immature stage of H. hampei was significantly shortened with increasing temperature. Furthermore, the lower developmental threshold (T0) and thermal summation (K) of the immature stage were 8.91 °C and 485.44 degree-days, respectively. The greatest longevity of female and male adults reached 115.77 and 26.50 days, respectively, at 18 °C. The highest fecundity was 29.00 eggs/female at 24 °C. The population parameters of H. hampei were analyzed on the basis of the age-stage, two-sex life table theory. According to the data, the parameters were significantly affected by temperature. The highest net reproductive rate (R0) was 13.32 eggs/individual at 24 °C. The highest intrinsic rate of increase (r) and finite rate of increase (λ) were calculated as 0.0401 and 1.0409 day-1, respectively, at a temperature of 27 °C. The shortest mean generation time (T) was 51.34 days at 27 °C. Overall, we provide a discussion on comprehensive biological information regarding H. hampei, thus providing basic knowledge for further research on this pest.

Simultaneous and Sequential Use of Molecular Targeted Agents Plus Immune Checkpoint Inhibitors for Advanced Hepatocellular Carcinoma: A Real-World Practice in China.

Purpose: Molecular targeted agents (MTAs) plus immune checkpoint inhibitors (ICIs) treatment for advanced hepatocellular carcinoma (HCC) has shown an exciting prospect. This study aimed to report the efficacy of the Simultaneous and Sequential use of them in a real-world practice. Patients and Methods: From April 2019 to December 2020, patients with advanced HCC in three Chinese medical centers receiving MTAs and ICIs as their initial systemic therapy were enrolled. Participants were classified into the Simultaneous group (treated with them simultaneously) and the Sequential group (treated with MTAs initially and added ICIs after tumor progression). Toxicity, tumor response, survival outcomes and prognostic factors were investigated. Results: One hundred and ten consecutive patients participated in the study (64 in the Simultaneous group and 46 in the Sequential group). A total of 93 (84.5%) patients experienced treatment-related adverse events (AEs), of which 55 (85.9%) in the Simultaneous group and 38 (82.6%) in the Sequential group (P=0.19). Grade 3/4 AEs were observed in 9 (8.2%) patients. Patients in the Simultaneous group achieved a higher objective response rate than those in the Sequential group (25.0% vs 4.3%, p=0.04). The median overall survival (OS) of the entire cohort was 14.8 [95% confidence interval (CI): 4.6-25.5] months and the OS rates at 6 and 12 months were 80.6% and 60.9%, respectively. Patients in the Simultaneous group achieved better survival outcomes than those in the Sequential group, but without statistically significant differences. Child-Pugh 6 scores (HR: 2.97, 95% CI: 1.33-6.61, P=0.008), tumor number ≤3 (HR: 0.18, 95% CI: 0.04-0.78, P=0.022), extrahepatic metastasis (HR: 3.05, 95% CI: 1.35-6.87, P=0.007) were independent prognostic factors for survival. Conclusion: The combined treatment of MTAs and ICIs shows good tumor response and survival outcomes with acceptable toxicity for advanced HCC in the real-world practice, in particular when they are applied simultaneously.

Edge-oriented phosphatizing engineering of 2D Ni-MOFs with a tailored d-band center for boosting catalytic activity.

Metal-organic framework (MOF)-based heterostructures have aroused widespread interest owing to their extensive compositional tunability and interesting catalytic properties. However, the precise edge-oriented growth of transition metal compounds at the edges of 2D MOFs to construct edge mode heterostructures remains a great challenge due to their inherent thermodynamic instability. Here, edge-oriented growth of Ni2P at the edges of a 2D Ni-MOF was achieved for the first time by precisely tuning the phosphorus source content and phosphating temperature. Owing to the formation of the edge mode Ni-MOF/Ni2P heterostructure, the as-prepared heterostructure showed upregulated d-band center, more robust 4-nitrophenol (4-NP) adsorption capacity, lowered energy barrier of the rate-determining step (RDS), and higher specific surface area, resulting in the best performance of the hydrogenation reduction of 4-NP to 4-aminophenol (4-AP) in the presence of non-precious metal catalysts.

Correction: Photodynamic antimicrobial chemotherapy with cationic phthalocyanines against Escherichia coli planktonic and biofilm cultures.

[This corrects the article DOI: 10.1039/C7RA06073D.].

Todani type III: like biliary dilatation with duodenal prolapse-a case report.

BACKGROUND: Biliary dilatation is a rare disease involving intrahepatic and extrahepatic biliary tract abnormalities. With the development of imaging technology, an increasing number of special cases have been diagnosed, which poses a challenge to the traditional classification method. CASE PRESENTATION: A 50-year-old woman was admitted to the hospital due to right upper quadrant pain for more than 10 days. The patient had previous episodes of similar symptoms, which were relieved after symptomatic treatment at a local community hospital. After the symptoms developed, she underwent a computed tomography scan at the local hospital, which showed biliary dilatation; thus, she was referred to our hospital for further treatment. After admission, her magnetic resonance imaging examination also suggested biliary dilatation, but abnormal signals were found in her duodenum. First, a duodenal diverticulum was considered. Later, endoscopic ultrasonography was conducted, and the results suggested that the dilated biliary tract had herniated into the duodenum. This type of lesion is most closely classified as a Todani type III lesion. The patient finally underwent choledochectomy and Roux­en­Y hepaticojejunostomy, and the postoperative pathology was consistent with our preoperative diagnosis. The patient was followed up for approximately 2 years, and no obvious postoperative complications were found. CONCLUSIONS: The manifestations of this case are relatively rare and involve one of the undiscussed categories of the Todani classification system; therefore, this case has certain clinical value. Moreover, there is no report similar to this experience in the previous literature.

CTCF-Induced lncRNA C5orf66-AS1 Facilitates the Progression of Triple-Negative Breast Cancer via Sponging miR-149-5p to Up-Regulate CTCF and CTNNB1 to Activate Wnt/ß-Catenin Pathway.

Triple-negative breast cancer (TNBC) represents one of the subtypes of breast cancer with high aggressiveness. Long noncoding RNAs (lncRNAs) are well-known to function as crucial regulators in human cancers which include TNBC. Nevertheless, the specific role of the lncRNA C5orf66-AS1 in TNBC is unclear. In this study, we tested C5orf66-AS1 expression in TNBC cells using quantitative real-time PCR (qRT-PCR) and used functional assays to detect cell behaviors, which showed that C5orf66-AS1 was highly expressed in TNBC cells and that C5orf66-AS1 knockdown attenuated cell proliferation, migration, and invasion while promoting cell apoptosis. Through a luciferase reporter assay, RNA immunoprecipitation (RIP) assay, and chromatin immunoprecipitation (ChIP) assay, we identified the binding capacity of C5orf66-AS1 to RNAs. Furthermore, miR-149-5p was proven to be sponged by C5orf66-AS1. CCCTC-binding factor (CTCF) was confirmed as the target of miR-149-5p and could transcriptionally activate C5orf66-AS1 expression in TNBC cells. We also discovered that C5orf66-AS1 activated the Wnt/ß-catenin signaling pathway by upregulating catenin beta 1 (CTNNB1). Importantly, CTNNB1 could be targeted by miR-149-5p. In rescue assays, it was proven that overexpressing CTCF and CTNNB1 or inhibiting miR-149-5p could totally reverse the inhibitory effect of silencing C5orf66-AS1 on TNBC progression. In short, the lncRNA C5orf66-AS1 acted as an oncogene to facilitate TNBC malignancy.

The ultrathin palladium nanosheets for sensitive and visual Hg2+ detection in the food chain.

The detection of mercury, one of the ten most dangerous chemicals, is significant to provide helpful information for assessing mercury toxicity and health risks. However, it is a challenge to explore simple, sensitive, accurate, and cheap Hg2+ detection methods. Noble metal nanomaterials are used for Hg2+ detection by the colorimetric method widely. Still, the pure noble metal materials' detection limit of Hg2+ is high, and sensitivity enhancement usually requires further complex modification. Here, we use a facile one-step route to synthesize ultra-thin two-dimensional palladium nanosheets (PdNS), which have high selectivity and sensitivity for Hg2+ detection by colorimetric method with a low detection limit (0.55 ppb). The detection of Hg2+ by PdNS involves multiple mechanisms, including the formation of amalgam and PdO to improve the peroxidase-mimic activity of PdNS and PdNS motor function to increase its collision probability with the detection reactant. The PdNS can be used to detect Hg2+ in various actual samples. The detection results are highly consistent with the data obtained by the atomic fluorescence spectrometer (AFS). Then, we developed a Hg2+ detection kit, which can realize simple, sensitive, and accurate Hg2+ detection by naked eye or cellphone at a meager cost (0.3 dollars each sample).

Improved Photodynamic Activity of Phthalocyanine by Adjusting the Chirality of Modified Amino Acids.

Herein, four zinc phthalocyanines (ZnPcs) with chiral lysine modification were synthesized. We found that the chirality of lysine and the chiral structure position strongly influence the properties of ZnPcs. Among the four ZnPcs, d-lysine-modified ZnPc through -NH2 on Cε [denoted N(ε)-d-lys-ZnPc] showed superior properties, including tumor enrichment, cancer cell uptake, and tumor retention capability, compared to the other three ZnPcs. Thus, chiral molecule modification is a simple and effective strategy to regulate the abovementioned properties to achieve a satisfactory antitumor outcome of drugs.

Synergistic anticancer theragnostic study of a core-shell structured galvanic cell.

The chemodynamic therapy (CDT) effect is restricted by the neutral pH environment in the tumor, also, the protein corona formed on the surface of the CDT catalyst reduces its activity. Here, we synthesized a core-shell CDT drug consisting of Fe/Fe3C core and mesoporous graphite carbon shell with biotin modification (denoted FeCNB). The shell and core form a galvanic cells in the physiological electrolyte solution to achieve high-efficiency CDT under physiological pH conditions. The mesoporous in the shell effectively separates the protein corona from the Fe/Fe3C, avoiding the influence of the protein corona on the catalyst. However, the mesoporous is permeable for the substrate and product of the catalytic reaction. FeCNB also has T2-magnetic resonance imaging (MRI) function and photothermal conversion ability under 808 nm laser irradiation. The tumor heating further improves the CDT effect to achieve a satisfactory synergistic photothermal therapy (PTT)/CDT outcome. In addition, FeCNB degrades in the microenvironment to ensure its excellent biocompatibility. It is the first study of CDT drug design and fabrication based on the mechanism of the galvanic cells.

The influence of modified molecular (D/L-serine) chirality on the theragnostics of PAMAM-based nanomedicine for acute kidney injury.

Acute kidney injury (AKI) is a severe clinical disease with extremely high morbidity and mortality. It is challenging to find a simple method for early detection of AKI and monitoring the treatment results. Renal tubular damage and inflammation are early events in AKI. Renal tubular damage is conducive to the accumulation of small-sized nanoparticles in the kidney, and inflammation is related to the excessive production of H2O2. Recent studies proved that chiral molecule modification of nanomaterials is a powerful strategy to regulate their biodistribution. Thus, L-serine and D-serine modified poly(amidoamine) (PAMAM) dendrimers were synthesized and used as fluorescent probe (NPSH) carriers to obtain L-SPH and D-SPH, respectively. D-SPH has a strong accumulation capability in the kidney of AKI mice. Then, the H2O2 fluorescent probe can detect the excessively produced H2O2 to generate fluorescence to diagnose AKI. Subsequently, the anti-inflammatory drug manganese pentacarbonyl bromide (CORM) was loaded in D-SPH to obtain D-SPHC with AKI theragnostic functions. Simultaneously, the D-SPHC fluorescence signal intensity change during the treatment can be used to monitor the recovery process. This study is the first report of chiral materials used in the diagnosis and treatment of AKI.

Polycyclodextrin as a linker for nanomedicine fabrication and synergistic anticancer application.

Polycyclodextrin (denoted PCD) composed of cyclodextrin monomer units and 1,3-diethoxypropan-2-ol containing many hydroxyl groups with lone pairs of electrons, easily coordinated with transition metals with empty orbitals. The CD unit can also provide host-guest binding sites for functional molecules. This article utilizes this feature of PCD for the first time as a "linker" to combine transition metal nanomaterials with synergistic functional molecules. We synthesized PCD with 50% CD monomer by epichlorohydrin cross-linking method. Utilizing the coordination effect of the hydroxyl group in PCD and the iron ion in photothermal nanoparticles (PB-Yb), the PCD is coated on its surface; simultaneously, CD in PCD can form a host-guest complex with adamantane-modified zinc phthalocyanine (Pc) photosensitizer. Using PCD as a "linker", PB-Yb and Pc (denoted PYPP) were combined to improve the solubility of PB-Yb, reduce the aggregation degree of Pc to increase their activity, and achieve photothermal and photodynamic synergistic tumor therapy.

Nanozyme with Robust Catalase Activity by Multiple Mechanisms and Its Application for Hypoxic Tumor Treatment.

Utilizing catalase-mimicking nanozymes to produce O2 is an effective method to overcome tumor hypoxia. However, it is challenging to fabricate nanozymes with ultrahigh catalytic activity. Palladium nanosheet (Pd NS), a photothermal agent for photothermal therapy (PTT), has superior catalase-mimicking activity. Here, titanium dioxide (TiO2 ) is used to modify Pd NS (denoted Pd@TiO2 ) by a simple one-step method to improve its catalytic activity about 8 times. The enhancement mechanism's fundamental insights are discussed through experiments and density functional theory calculations. Next, zinc phthalocyanine is loaded on Pd@TiO2 to form a nanomotor (denoted PTZCs) with the synergistic activities of photodynamic therapy and PTT. PTZCs inherit the catalase activity of Pd@TiO2 to facilitate the decomposition of endogenous H2 O2 to O2 , which can relieve tumor hypoxia and propel PTZC migration to expand the reach of PTZCs, further enhancing its synergistic treatment outcome both in vitro and in vivo. It is proposed that this work can provide a simple and effective strategy for catalytic activity enhancement and bring a critical new perspective to studying and guiding the nanozyme design.

Study on Fabrication and Properties of Graphite/Al Composites by Hot Isostatic Pressing-Rolling Process.

Graphite/Al composites have attracted much attrition due to their excellent thermal properties. However, the improvement of thermal conductivity (TC) is limited by the difficulty in controlling the orientation of graphite and the poor wettability between graphite and aluminum. In this study, a novel process for fabricating the Graphite/Al composites is proposed, which involves fabricating graphite film and aluminum foil into laminate material. Then, taking a rolling method, the fractured and well oriented graphite film can help the composite achieve high TC while maintaining a certain strength. The result reveals that both single and total reduction have a significant influence on the diameter and orientation of the graphite, and by adjusting the process parameters, composites with high TC can be acquired at a relatively low reinforcement volume. This near-net-forming process can directly meet the thickness requirements for electronic packaging and avoids the exposure of graphite to the surface during secondary processing, which is promising to promote the application for high TC Graphite/Al composites in thermal management.

Near-infrared light-controllable MXene hydrogel for tunable on-demand release of therapeutic proteins.

Precise delivery of therapeutic protein drugs that specifically modulate desired cellular responses is critical in clinical practice. However, the spatiotemporal regulation of protein drugs release to manipulate the target cell population in vivo remains a huge challenge. Herein, we have rationally developed an injectable and Near-infrared (NIR) light-responsive MXene-hydrogel composed of Ti3C2, agarose, and protein that enables flexibly and precisely control the release profile of protein drugs to modulate cellular behaviors with high spatiotemporal precision remotely. As a proof-of-concept study, we preloaded hepatic growth factor (HGF) into the MXene@hydrogel (MXene@agarose/HGF) to activate the c-Met-mediated signaling by NIR light. We demonstrated NIR light-instructed cell diffusion, migration, and proliferation at the user-defined localization, further promoting angiogenesis and wound healing in vivo. Our approach's versatility was validated by preloading tumor necrotic factor-α (TNF-α) into the composite hydrogel (MXene@agarose/TNF-α) to promote the pro-apoptotic signaling pathway, achieving the NIR light-induced programmed cell deaths (PCD) of tumor spheroids. Taking advantage of the deep-tissue penetrative NIR light, we could eradicate the deep-seated tumors in a xenograft model exogenously. Therefore, the proposed MXene-hydrogel provides the impetus for developing therapeutic synthetic materials for light-controlled drug release under thick tissue, which will find promising applications in regenerative medicine and tumor therapy. STATEMENT OF SIGNIFICANCE: Current stimuli-responsive hydrogels for therapeutic proteins delivery mainly depend on self-degradation, passive diffusion, or the responsiveness to cues relevant to diseases. However, it remains challenging to spatiotemporally deliver protein-based drugs to manipulate the target cell population in vivo in an "on-demand" manner. Therefore, we have rationally constructed an injectable and Near-infrared (NIR) light-responsive composite hydrogel by embedding Ti3C2 MXene and protein drugs within an agarose hydrogel to enable the remote control of protein drugs delivery with high spatiotemporal precision. The NIR light-controlled release of the growth factor or cytokine has been carried out to regulate receptor-mediated cellular behaviors under deep tissue for skin wound healing or cancer therapy. This system will provide the potential for precision medicine through the development of intelligent drug delivery systems.