HMGA1 sensitizes esophageal squamous cell carcinoma to mTOR inhibitors through the ETS1-FKBP12 axis.

Esophageal carcinoma is amongst the prevalent malignancies worldwide, characterized by unclear molecular classifications and varying clinical outcomes. The PI3K/AKT/mTOR signaling, one of the frequently perturbed dysregulated pathways in human malignancies, has instigated the development of various inhibitory agents targeting this pathway, but many ESCC patients exhibit intrinsic or adaptive resistance to these inhibitors. Here, we aim to explore the reasons for the insensitivity of ESCC patients to mTOR inhibitors. We assessed the sensitivity to rapamycin in various ESCC cell lines by determining their respective IC50 values and found that cells with a low level of HMGA1 were more tolerant to rapamycin. Subsequent experiments have supported this finding. Through a transcriptome sequencing, we identified a crucial downstream effector of HMGA1, FKBP12, and found that FKBP12 was necessary for HMGA1-induced cell sensitivity to rapamycin. HMGA1 interacted with ETS1, and facilitated the transcription of FKBP12. Finally, we validated this regulatory axis in in vivo experiments, where HMGA1 deficiency in transplanted tumors rendered them resistance to rapamycin. Therefore, we speculate that mTOR inhibitor therapy for individuals exhibiting a reduced level of HMGA1 or FKBP12 may not work. Conversely, individuals exhibiting an elevated level of HMGA1 or FKBP12 are more suitable candidates for mTOR inhibitor treatment.

Mesothelin CAR-T cells expressing tumor-targeted immunocytokine IL-12 yield durable efficacy and fewer side effects.

Chimeric antigen receptor (CAR)-modified T cell therapy has achieved remarkable efficacy in treating hematological malignancies, but it confronts many challenges in treating solid tumors, such as the immunosuppressive microenvironment of the solid tumors. These factors reduce the antitumor activity of CAR-T cells in clinical trials. Therefore, we used the immunocytokine interleukin-12 (IL-12) to enhance the efficacy of CAR-T cell therapy. In this study, we engineered CAR-IL12R54 T cells that targeted mesothelin (MSLN) and secreted a single-chain IL-12 fused to a scFv fragment R54 that recognized a different epitope on mesothelin. The evaluation of the anti-tumor activity of the CAR-IL12R54 T cells alone or in combination with anti-PD-1 antibody in vitro and in vivo was followed by the exploration of the functional mechanism by which the immunocytokine IL-12 enhanced the antitumor activity. CAR-IL12R54 T cells had potency to lyse mesothelin positive tumor cells in vitro. In vivo studies demonstrated that CAR-IL12R54 T cells were effective in controlling the growth of established tumors in a xenograft mouse model with fewer side effects than CAR-T cells that secreted naked IL-12. Furthermore, combination of PD-1 blockade antibody with CAR-IL12R54 T cells elicited durable anti-tumor responses. Mechanistic studies showed that IL12R54 enhanced Interferon-γ (IFN-γ) production and dampened the activity of regulatory T cells (Tregs). IL12R54 also upregulated CXCR6 expression in the T cells through the NF-κB pathway, which facilitated T cell infiltration and persistence in the tumor tissues. In summary, the studies provide a good therapeutic option for the clinical treatment of solid tumors.

Enhanced multi-metals stabilization: Synergistic insights from hydroxyapatite and peroxide dosing strategies.

Sediment contamination by heavy metals is a pressing environmental concern. While in situ metal stabilization techniques have shown promise, a great challenge remains in the simultaneous immobilization of multi-metals co-existing in contaminated sediments. This study aims to address this challenge by developing a practical method for stabilizing multi-metals by hydroxyapatite and calcium peroxide (HAP/CaO2) dosing strategies. Results showed that dosing 15.12 g of HAP/CaO2 at a ratio of 3:1 effectively transformed labile metals into stable fractions, reaching reaction kinetic equilibrium within one month with a pseudo-second-order kinetic (R2 > 0.98). The stable fractions of Nickel (Ni), Chromium (Cr), and lead (Pb) increased by approximately 16.9 %, 26.7 %, and 21.9 %, respectively, reducing heavy metal mobility and ensuring leachable concentrations complied with the stringent environmental Class I standard. Mechanistic analysis indicated that HAP played a crucial role in Pb stabilization, exhibiting a high rate of 0.0176 d-1, while Cr and Ni stabilization primarily occurred through the formation of hydroxide precipitates, as well as the slowly elevated pH (>8.5). Importantly, the proposed strategy poses a minimal environmental risk to benthic organisms exhibits almost negligible toxicity towards Vibrio fischeri and the Chironomus riparius, and saves about 71 % of costs compared to kaolinite. These advantages suggest the feasibility of HAP/CaO2 dosing strategies in multi-metal stabilization in contaminated sediments.

Investigating the Influence of Impurity Defects on the Adsorption Behavior of Hydrated Sc3+ on the Kaolinite (001) Surface Using Density Functional Theory.

In natural kaolinite lattices, Al3+ can potentially be substituted by cations such as Mg2+, Ca2+, and Fe3+, thereby influencing its adsorption characteristics towards rare earth elements like Sc3+. Density functional theory (DFT) has emerged as a crucial tool in the study of adsorption phenomena, particularly for understanding the complex interactions of rare earth elements with clay minerals. This study employed DFT to investigate the impact of these three dopant elements on the adsorption of hydrated Sc3+ on the kaolinite (001) Al-OH surface. We discerned that the optimal adsorption configuration for hydrated Sc3+ is Sc(H2O)83+, with a preference for adsorption at the deprotonated Ou sites. Among the dopants, Mg doping exhibited superior stability with a binding energy of -4.311 eV and the most negative adsorption energy of -1104.16 kJ/mol. Both Mg and Ca doping enhanced the covalency of the Al-O bond, leading to a subtle shift in the overall density of states towards higher energies, thereby augmenting the reactivity of the O atoms. In contrast, Fe doping caused a pronounced shift in the density of states towards lower energies. Compared to the undoped kaolinite, Mg and Ca doping further diminished the adsorption energy of hydrated Sc3+ and increased its coordination number, while Fe doping elevated the adsorption energy. This study offers profound insights into understanding the role of dopant elements in the adsorption of hydrated Sc3+ on kaolinite.

Study on the adsorption of Zn(II) and Cu(II) in acid mine drainage by fly ash loaded nano-FeS.

Aiming at the acid mine drainage (AMD) in zinc, copper and other heavy metals treatment difficulties, severe pollution of soil and water environment and other problems. Through the ultrasonic precipitation method, this study prepared fly ash-loaded nano-FeS composites (nFeS-F). The effects of nFeS-F dosage, pH, stirring rate, reaction time and initial concentration of the solution on the adsorption of Zn(II) and Cu(II) were investigated. The data were fitted by Lagergren first and second-order kinetic equations, Internal diffusion equation, Langmuir and Freundlich isotherm models, and combined with SEM, TEM, FTIR, TGA, and XPS assays to reveal the mechanism of nFeS-F adsorption of Zn(II) and Cu(II). The results demonstrated that: The removal of Zn(II) and Cu(II) by nFeS-F could reach 83.36% and 70.40%, respectively (The dosage was 8 g/L, pH was 4, time was 150 min, and concentration was 100 mg/L). The adsorption process, mainly chemical adsorption, conforms to the Lagergren second-order kinetic equation (R2 = 0.9952 and 0.9932). The adsorption isotherms have a higher fitting degree with the Langmuir model (R2 = 0.9964 and 0.9966), and the adsorption is a monolayer adsorption process. This study can provide a reference for treating heavy metals in acid mine drainage and resource utilization of fly ash.

Spinal Lymphatic Dysfunction Aggravates the Recovery Process After Spinal Cord Injury.

We aimed to evaluate the role of the spinal lymphatic system in spinal cord injury and whether it has an impact on recovery after spinal cord injury. Flow cytometry was used to evaluate the changes in the number of microvesicles after spinal cord injury. Evans blue extravasation was used to evaluate the function of the lymphatic system. Evans blue extravasation and immunofluorescence were used to evaluate the permeability of blood spinal cord barrier. The spinal cord edema was evaluated by dry and wet weight.Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay was used to evaluate apoptosis after spinal cord injury. Nuclear factor-kappa B pathway was detected by Western blot. Behavioral tests were used to evaluate limb function. Microvesicles released after spinal cord injury can enter the thoracic duct and then enter the blood through the lymph around the spine. After ligation of the thoracic duct, it can aggravate the neuropathological manifestations and limb function after spinal cord injury. The potential mechanism may involve nuclear factor-kappa B pathway.

Brain-derived extracellular vesicles mediate systemic coagulopathy and inflammation after traumatic brain injury.

Traumatic brain injury (TBI) can induce systemic coagulopathy and inflammation, thereby increasing the risk of mortality and disability. However, the mechanism causing systemic coagulopathy and inflammation following TBI remains unclear. In prior research, we discovered that brain-derived extracellular vesicles (BDEVs), originating from the injured brain, can activate the coagulation cascade and inflammatory cells. In this study, we primarily investigated how BDEVs affect systemic coagulopathy and inflammation in peripheral circulation. The results of cytokines and coagulation function indicated that BDEVs can lead to systemic coagulopathy and inflammation by influencing inflammatory factors and chemokines within 24 h. Furthermore, according to flow cytometry and blood cell counter results, we found that BDEVs induced changes in the blood count such as a reduced number of platelets and leukocytes and an increased percentage of neutrophils, macrophages, activated platelets, circulating platelet-EVs, and leukocyte-derived EVs. We also discovered that eliminating circulating BDEVs with lactadherin helped improve coagulopathy and inflammation, relieved blood cell dysfunction, and decreased the circulating platelet-EVs and leukocyte-derived EVs. Our research provides a novel viewpoint and potential mechanism of TBI-associated secondary damage.

Insight into the role of heterogeneous Fenton-like catalyst FeCo-γ-Al2O3 with dual electron-rich centers for Ni-EDTA removal.

To enhance the polarization distribution of electron cloud density on the catalyst surface, we have introduced a novel bimetallic-substituted dual-reaction center (DRC) catalyst (FeCo-γ-Al2O3) comprising iron (Fe) and cobalt (Co) for the decomplexation and mineralization of heavy metal complex Ni-EDTA in this study. Compared to the catalysts doped solely with Fe or Co, the bimetal-doped catalyst offered several advantages, including enhanced electron cloud polarization distribution, additional electron transfer pathway, and improved capacity of free radical generation. Through DFT calculations and EPR tests, we have elucidated the influences of the catalyst's adsorption toward Ni-EDTA and its decomplexation products on the electron transfer between the pollutant and the catalyst. The competition between the pollutants and H2O2 affects the generation of free radicals in both electron-rich Fe and Co centers as well as electron-deficient Al center. Building on these findings, we have proposed a plausible removal mechanism of Ni-EDTA using the heterogeneous Fenton-like catalyst FeCo-γ-Al2O3. This study sheds light on the potential of FeCo-γ-Al2O3 as a DRC catalyst and emphasizes the significance of pollutant characteristics in determining the catalyst's performance.

Scoparone attenuates glioma progression and improves the toxicity of temozolomide by suppressing RhoA/ROCK1 signaling.

BACKGROUND: Glioma, a type of malignant brain tumor, has become a challenging health issue globally in recent years. METHODS: In this study, we investigated the potential therapeutic role of scoparone in glioma and the underlying mechanism. Initially, transcriptome sequencing was conducted to identify genes that exhibited differential expression in glioma cells treated with scoparone compared to untreated cells. Subsequently, the impact of scoparone on the proliferation, migration, and invasion of glioma cells was assessed in vitro using a range of assays including cell viability, colony formation, wound healing, and transwell assays. Moreover, the apoptotic effects of scoparone on glioma cells were evaluated through flow cytometry and western blot analysis. Furthermore, we established a glioma xenograft mouse model to assess the in vivo antitumor activity of scoparone. Lastly, by integrating transcriptome analysis, we endeavored to unravel the molecular mechanisms underlying the observed antitumor effects of scoparone by examining the expression levels of RhoA/ROCK1 signaling pathway components using western blot analysis and qRT-PCR. RESULTS: Our transcriptome sequencing results revealed that scoparone significantly downregulated RhoA/ROCK1 signaling in glioma cells. Furthermore, scoparone treatment inhibited glioma cell proliferation, migration, and invasion, and promoted cell apoptosis in vitro. Moreover, scoparone reduced tumor growth and prolonged survival in a glioma xenograft mouse model, and improved the toxicity of temozolomide. Finally, our results showed that the antitumor effects of scoparone were mediated by the suppression of RhoA/ROCK1 signaling. CONCLUSION: Scoparone could be a promising therapeutic agent for glioma by suppressing RhoA/ROCK1 signaling. These findings pave the way for future research endeavors aimed at the development and optimization of scoparone-based therapeutic strategies.

Nomogram based on CMTM6 expression and clinical characteristics to predict postoperative overall survival in patients with hepatocellular carcinoma.

BACKGROUND: The purpose of this study was to investigate the expression of CMTM6 in HCC tissues and its prognostic value, and to try to develop a nomogram prognostic model based on CMTM6. METHODS: In this retrospective study, immunohistochemical (IHC) staining was performed in 178 patients who underwent radical hepatectomy in the same surgical team. R software was used to construct the nomogram model. The Bootstrap sampling method was used for internal validation. RESULTS: CMTM6 is significantly expressed in HCC tissues and is closely associated with decreased overall survival (OS). PVTT (HR = 6.2, 95% CI: 3.06 12.6, P<0.001), CMTM6 (HR=2.30, 95% CI: 1.27 4.0, P=0.006) and MVI (HR=10.8, 95% CI: 4.19-27.6, P<0.001) were independent predictors of OS. The nomogram combined with CMTM6, PVTT and MVI was more predictive than the traditional TNM scoring system, and the prediction effects of 1-year and 3-year OS were accurate. CONCLUSIONS: The prognosis of a patient may be predicted using high levels of CMTM6 expression in HCC tissues, and the nomogram model including CMTM6 expression has the best predictive ability.

Akkermansia muciniphila protects the intestine from irradiation-induced injury by secretion of propionic acid.

Intestinal dysbiosis frequently occurs in abdominal radiotherapy and contributes to irradiation (IR)-induced intestinal damage and inflammation. Akkermansia muciniphila (A. muciniphila) is a recently characterized probiotic, which is critical for maintaining the dynamics of the intestinal mucus layer and preserving intestinal microbiota homeostasis. However, the role of A. muciniphila in the alleviation of radiation enteritis remains unknown. In this study, we reported that the abundance of A. muciniphila was markedly reduced in the intestines of mice exposed to abdominal IR and in the feces of patients who received abdominal radiotherapy. Abundance of A. muciniphila in feces of radiotherapy patients was negatively correlated with the duration of diarrhea in patients. Administration of A. muciniphila substantially mitigated IR-induced intestinal damage and prevented mouse death. Analyzing the metabolic products of A. muciniphila revealed that propionic acid, a short-chain fatty acid secreted by the microbe, mediated the radioprotective effect. We further demonstrated that propionic acid bound to G-protein coupled receptor 43 (GRP43) on the surface of intestinal epithelia and increased histone acetylation and hence enhanced the expression of tight junction proteins occludin and ZO-1 and elevated the level of mucins, leading to enhanced integrity of intestinal epithelial barrier and reduced radiation-induced intestinal damage. Metformin, a first-line agent for the treatment of type II diabetes, promoted intestinal epithelial barrier integrity and reduced radiation intestinal damage through increasing the abundance of A. muciniphila. Together, our results demonstrated that A. muciniphila plays a critical role in the reduction of abdominal IR-induced intestinal damage. Application of probiotics or their regulators, such as metformin, could be an effective treatment for the protection of radiation exposure-damaged intestine.

The Design of a Low-Noise, High-Speed Readout-Integrated Circuit for Infrared Focal Plane Arrays.

This paper describes the design of a low-noise, high-speed readout-integrated circuit for use in InGaAs infrared focal plane arrays, and analyzes the working principle and noise index of the pixel circuit in detail. The design fully considers the dynamic range, noise, and power consumption of the pixel circuit in which a capacitance transimpedance amplifier structure is adopted as the input stage circuit, and chip fabrication via an XFAB 0.18 µm CMOS process is successfully realized. The ROIC adopts monolithic integration and implements various functions, such as windowing, subsampling, and different integration and readout modes. The ROIC reached an array scale of 32 × 32, a frame rate of 100 Hz, and a readout rate of 20 Mbps with an analog power consumption of less than 52 mW. The measurement results show that the input reference noise can be reduced to 143 e- via the CDS, and the fully customized scheme has certain advantages in the research of high-performance ROICs.

Stimulated thyroglobulin and pre-ablation antithyroglobulin antibody products can predict the response to radioiodine therapy of TgAb-positive differentiated thyroid cancer patients: a retrospective study.

Objective: We aimed to explore the predictive value of stimulated thyroglobulin (sTg) and pre-ablation antithyroglobulin (pa-TgAb) products for the effect of radioiodine therapy (RAIT) on TgAb-positive differentiated thyroid cancer (DTC) patients. Methods: In this study, we enrolled 265 patients with TgAb-positive DTC who underwent RAIT after total thyroidectomy (TT). Based on the last follow-up result, the patients were divided into two groups: the excellent response (ER) group and the non-excellent response (NER) group. We analyzed the factors related to the effect of RAIT. Results: The ER group consisted of 197 patients. The NER group consisted of 68 patients. For the univariate analysis, we found that the maximal tumor diameter, whether with extrathyroidal extension (ETE), bilateral or unilateral primary lesion, multifocality, preoperative TgAb (preop-TgAb), pa-TgAb, sTg × pa-TgAb, initial RAIT dose, N stage, and surgical extent (modified radical neck dissection or not), showed significant differences between the ER group and NER group (all p-values <0.05). The receiver operating characteristic (ROC) curves showed that the cutoff value was 724.25 IU/ml, 424.00 IU/ml, and 59.73 for preop-TgAb, pa-TgAb, and sTg × pa-TgAb, respectively. The multivariate logistic regression analysis results indicated that pa-TgAb, sTg × pa-TgAb, initial RAIT dose, and N stage were independent risk factors for NER (all p-values <0.05). For the Kaplan-Meier analysis of disease-free survival (DFS), the median DFS of the patients with sTg × pa-TgAb < 59.73 and initial RAIT dose ≤ 100 mCi was significantly longer than that of the patients with sTg × pa-TgAb ≥ 59.73 (50.27 months vs. 48.59 months, p = 0.041) and initial RAIT dose >100 mCi (50.50 months vs. 38.00 months, p = 0.030). Conclusion: We found the sTg and pa-TgAb conducts is a good predictor of the efficacy of RAIT in TgAb-positive DTC patients. It can play a very positive and important role in optimizing treatment, improving prognosis, and reducing the burden of patients.

Exaggerated interaction of biofilm-developed microplastics and contaminants in aquatic environments.

Biofilm-developed microplastics (MPs) may serve as important vectors for contaminants in aquatic environments. Elucidating the interactions between biofilm-developed MPs and coexisting contaminants is crucial for understanding the vector capacities of MPs. However, little is known about how the adverse effects of contaminants on MP surface-colonized biofilms influence their vector capacity. In this study, we aimed to investigate the interaction mechanism of biofilms colonizing the surface of MPs with coexisting contaminants using microcosm experiments and biofilm characterization techniques. The results indicated that the biofilm biomass on polystyrene increased over time, providing an additional abundance of oxygen-containing functional groups and promoting Cd accumulation by biofilm-developed polystyrene. Moreover, as a coexisting contaminant, Cd exerted adverse effects such as additional mortality of microorganisms and senescence and MP-colonized biofilm shedding. Consequently, the contaminant vector capacity of biofilm-developed MPs could be mitigated. Thus, the adverse effects of coexisting contaminants on biofilms influenced the ability of MPs to act as vectors in aquatic environments. Neglecting the negative effects of contaminants on biofilms may lead to an overestimation of the contaminant vector capacity of biofilm-developed MPs. This study provides support for more accurate assessment of the interactions between biofilm-developed MPs as vectors and contaminants in aquatic environments.

Water Consolidation Performance of Acrylic-Polymer-Modified Materials and Their Concrete Impermeability Repair Characteristics.

Acrylic materials exhibit favorable grouting repair performance. However, their curing products are easily inclined to drying shrinkage, and their concrete impermeability repair characteristics have seldom been investigated. To improve material properties, reveal the impermeability repair mechanism, and address drying shrinkage, this study proposed the addition of styrene-acrylate copolymer emulsion (styrene-acrylic emulsion) to the grouting material to prepare two-component acrylate grouting materials. Using orthogonal and single-factor tests combined with physical and mechanical properties, the mechanical properties and impermeability repair performance (physical and mechanical properties combined) of grouting materials were analyzed and studied, and the optimal ratio of each component of acrylate grouting materials was determined. Results show that (1) the hydrogel produced by the reaction of sodium methacrylate with hydroxyethyl acrylate has good physical and mechanical properties. (2) With the increase in the accelerator dosage, the setting time of slurry initially decreases and then increases; as the initiator dosage increases, the setting time of slurry decreases, which is negatively correlated with the initiator dosage. (3) Talcum powder can improve the physical and chemical properties of gel and enhance the reliability and durability of acrylate grouting materials, and the comprehensive performance is the best at a dosage of 3%. (4) Styrene-acrylic emulsion can increase the solid content and reduce the volume drying shrinkage when added to grouting materials. The fractured impermeable specimens were repaired by grouting with prepared acrylate grouting materials and cured for 24 h for the impermeability test, and the water pressure for the 24 h impermeability repair was 1.0 MPa. This study's results provide important reference and basis for revealing the impermeability principle of acrylate grouting materials and evaluating their impermeability.

Development of a novel three-dimensional biofilm-electrode system (3D-BES) loaded with Fe-modified biochars for enhanced pollutants removal in landfill leachate.

Different mass ratio iron (Fe)-loaded biochars (FeBCs) were prepared from food waste and used in the three-dimensional biofilm-electrode systems (3D-BES) as particular electrodes for landfill leachate treatment. Compared to the unmodified biochar (BC), specific surface area of Fe-loaded biochars (FeBC-3 with a Fe: biochar of 0.2:1) increased from 63.01 m2/g to 184.14 m2/g, and pore capacity increased from 0.038 cm3/g to 0.111 cm3/g. FeBCs provided more oxygen-containing functional groups and exhibited excellent redox properties. Installed with FeBC-3 as particular electrode, both NH4+-N and chemical oxygen demand COD removals in 3D-BESs were well fitted with the pseudo-first-order model, with the maximum removal efficiencies of 98.6 % and 95.5 %, respectively. The batch adsorption kinetics experiments confirmed that the maximum NH4+-N (7.5 mg/g) and COD (21.8 mg/g) adsorption capacities were associated closely with the FeBC-3 biochar. In contrast to the 3D-BES with the unmodified biochar, Fe-loaded biochars significantly increased the abundance of microorganisms being capable of removing organics and ammonia. Meanwhile, the increased content of dehydrogenase (DHA) and electron transport system activity (ETSA) evidenced that FeBCs could enhance microbial internal activities and regulate electron transfer process among functional microorganisms. Consequently, it is concluded that Fe-loaded biochar to 3D-BES is effective in enhancing pollutant removals in landfill leachate and provided a reliable and effective strategy for refractory wastewater treatment.

Adsorption of Sc on the Surface of Kaolinite (001): A Density Functional Theory Study.

The adsorption behavior of Sc on the surface of kaolinite (001) was investigated using the density functional theory via the generalized gradient approximation plane-wave pseudopotential method. The highest coordination numbers of hydrated Sc3+, ScOH2+, and ScOH2 + species are eight, six, and five, respectively. The adsorption model was based on ScOH2H2O5+, which has the most stable ionic configuration in the liquid phase. According to the adsorption energy and bonding mechanism, the adsorption of Sc ionic species can be categorized into outer layer and inner layer adsorptions. We found that the hydrated Sc ions were mainly adsorbed on the outer layer of the kaolinite (001)Al-OH and (00-1)Si-O surfaces through hydrogen bonding while also being adsorbed on the inner layer of the deprotonated kaolinite (001)Al-OH surface through coordination bonding. The inner layer adsorption has three adsorption configurations, with the lying hydroxyl group (Ol) position having the lowest adsorption energy (-653.32 KJ/mol). The adsorption energy for the inner layer is lower compared to the outer layer, while the extent of deprotonation is limited. This is because the deprotonation of the inner adsorption layer is energetically unfavorable. We speculate that Sc ions species predominantly adsorb onto the surface of kaolinite (001) in an outer layer configuration.

Green biomanufacturing in recombinant collagen biosynthesis: trends and selection in various expression systems.

Collagen, classically derived from animal tissue, is an all-important protein material widely used in biomedical materials, cosmetics, fodder, food, etc. The production of recombinant collagen through different biological expression systems using bioengineering techniques has attracted significant interest in consideration of increasing market demand and the process complexity of extraction. Green biomanufacturing of recombinant collagen has become one of the focus topics. While the bioproduction of recombinant collagens (type I, II, III, etc.) has been commercialized in recent years, the biosynthesis of recombinant collagen is extremely challenging due to protein immunogenicity, yield, degradation, and other issues. The rapid development of synthetic biology allows us to perform a heterologous expression of proteins in diverse expression systems, thus optimizing the production and bioactivities of recombinant collagen. This review describes the research progress in the bioproduction of recombinant collagen over the past two decades, focusing on different expression systems (prokaryotic organisms, yeasts, plants, insects, mammalian and human cells, etc.). We also discuss the challenges and future trends in developing market-competitive recombinant collagens.

Programming Affinity for Precise Tumor Recognition with Allosteric Nanosensing-Circles.

Although many smart probes for precise tumor recognition have been reported, the challenge of "on-target, off-tumor" remains. Therefore, we herein report the fabrication of a series of allosterically tunable DNA nanosensing-circles (NSCs). The recognition affinity of NSCs is programmed through sensitivity to tumor microenvironment (TME) hallmarks such as small molecules, acidity, or oncoproteins. Because of their special programming conditions and active targeting capabilities, NSCs can overcome the obstacles noted above, thus achieving precise tumor recognition. Results from in vitro analysis demonstrated that NSCs obtain their recognition ability through allosteric regulation after sensing TME hallmarks. Furthermore, in vivo imaging indicated that NSCs enable precise tumor imaging. These results demonstrate that our NSCs will be promising tools for precise tumor imaging and therapy.