Harnessing the potential of hydrogels for advanced therapeutic applications: current achievements and future directions.

The applications of hydrogels have expanded significantly due to their versatile, highly tunable properties and breakthroughs in biomaterial technologies. In this review, we cover the major achievements and the potential of hydrogels in therapeutic applications, focusing primarily on two areas: emerging cell-based therapies and promising non-cell therapeutic modalities. Within the context of cell therapy, we discuss the capacity of hydrogels to overcome the existing translational challenges faced by mainstream cell therapy paradigms, provide a detailed discussion on the advantages and principal design considerations of hydrogels for boosting the efficacy of cell therapy, as well as list specific examples of their applications in different disease scenarios. We then explore the potential of hydrogels in drug delivery, physical intervention therapies, and other non-cell therapeutic areas (e.g., bioadhesives, artificial tissues, and biosensors), emphasizing their utility beyond mere delivery vehicles. Additionally, we complement our discussion on the latest progress and challenges in the clinical application of hydrogels and outline future research directions, particularly in terms of integration with advanced biomanufacturing technologies. This review aims to present a comprehensive view and critical insights into the design and selection of hydrogels for both cell therapy and non-cell therapies, tailored to meet the therapeutic requirements of diverse diseases and situations.

Color Night Light Remote Sensing Images Generation Using Dual-Transformation.

Traditional night light images are black and white with a low resolution, which has largely limited their applications in areas such as high-accuracy urban electricity consumption estimation. For this reason, this study proposes a fusion algorithm based on a dual-transformation (wavelet transform and IHS (Intensity Hue Saturation) color space transform), is proposed to generate color night light remote sensing images (color-NLRSIs). In the dual-transformation, the red and green bands of Landsat multi-spectral images and "NPP-VIIRS-like" night light remote sensing images are merged. The three bands of the multi-band image are converted into independent components by the IHS modulated wavelet transformed algorithm, which represents the main effective information of the original image. With the color space transformation of the original image to the IHS color space, the components I, H, and S of Landsat multi-spectral images are obtained, and the histogram is optimally matched, and then it is combined with a two-dimensional discrete wavelet transform. Finally, it is inverted into RGB (red, green, and blue) color images. The experimental results demonstrate the following: (1) Compared with the traditional single-fusion algorithm, the dual-transformation has the best comprehensive performance effect on the spatial resolution, detail contrast, and color information before and after fusion, so the fusion image quality is the best; (2) The fused color-NLRSIs can visualize the information of the features covered by lights at night, and the resolution of the image has been improved from 500 m to 40 m, which can more accurately analyze the light of small-scale area and the ground features covered; (3) The fused color-NLRSIs are improved in terms of their MEAN (mean value), STD (standard deviation), EN (entropy), and AG (average gradient) so that the images have better advantages in terms of detail texture, spectral characteristics, and clarity of the images. In summary, the dual-transformation algorithm has the best overall performance and the highest quality of fused color-NLRSIs.

Design, synthesis, and anti-tumor activity of derivatives of ring A and C-28 of asiatic acid.

Based on computer-aided drug design (CADD), the active groups of the known active small molecule compounds that can bind to EGFR target protein were analyzed through the molecular docking method. Then, 12 novel asiatic acid derivatives were synthesized by introducing active groups at ring A and C-28 positions of asiatic acid. The structures of these novel compounds were determined by NMR and MS. Furthermore, the anti-tumor activities of these derivatives on human lung cancer cells (A549) and human breast cancer cells (MCF-7) were evaluated by MTT assay. In conclusion, compounds I4 and II3 have stronger anti-cancer activity than parent compounds, the activities were stronger than gefitinib and comparable to afatinib, which may be potential candidate compounds for tumor therapy.

Simultaneous inorganic nitrogen and phosphate removal by aerobic-heterotrophic fungus Fusarium keratoplasticum FSP1: Performance, pathway and application.

Fungi with multiple contaminant removal function have rarely been studied. Here, a novel fungal strain Fusarium keratoplasticum FSP1, which was isolated from halophilic granular sludge, is reported for first time to perform simultaneous nitrogen and phosphate removal. The strain showed wide adaptability under C/N ratios of 30-35, salinities of 0 %-3 % (m/v), and pH of 7.5-9.5. The maximum removal rates of ammonium, nitrate and nitrite were 4.43, 4.01 and 2.97 mg N/L/h. The nitrogen balance, enzyme activity and substrate conversion experiments demonstrated a single strain FSP1 can assimilate inorganic nitrogen and convert inorganic nitrogen to gaseous nitrogen through heterotrophic nitrification or aerobic denitrification. About 39 %-42 % of the degraded phosphorus was in the extracellular polymeric substances (EPS). Orthophosphate was the main phosphorus species in the cell, whereas phosphate monoester and diester were in the EPS. The novel strain FSP1 is a potential candidate for wastewater treatment.

A novel tumor 4-driver gene signature for the prognosis of hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC), the main type of liver cancer, is the second most lethal tumor worldwide, with a 5-year survival rate of only 18%. Driver genes facilitate cancer cell growth and spread in the tumor microenvironment. Here, a comprehensive driver gene signature for the prognosis of HCC was developed. Methods: HCC driver genes were analyzed comprehensively to develop a better prognostic signature. The dataset of HCC patients included mRNA sequencing data and clinical information from the TCGA, the ICGC, and the Guangxi Medical University Cancer Hospital cohorts. First, LASSO was performed to develop a prognostic signature for differentially expressed driver genes in the TCGA cohort. Then, the robustness of the signature was assessed using survival and time-dependent ROC curves. Furthermore, independent predictors were determined using univariate and multivariate Cox regression analyses. Stepwise multi-Cox regression analysis was employed to identify significant variables for the construction of a nomogram that predicts survival rates. Functional analysis by Spearman correlation analysis, enrichment analysis (GO, KEGG, and GSEA), and immunoassay (ssGSEA and xCell) were performed. Result: A 4-driver gene signature (CLTC, DNMT3A, GMPS, and NRAS) was successfully constructed and showed excellent predictive efficiency in three cohorts. The nomogram indicated high predictive accuracy for the 1-, 3-, and 5-year prognoses of HCC patients, which included clinical information and risk score. Enrichment analysis revealed that driver genes were involved in regulating oncogenic processes, including the cell cycle and metabolic pathways, which were associated with the progression of HCC. ssGSEA and xCell showed differences in immune infiltration and the immune microenvironment between the two risk groups. Conclusion: The 4-driver gene signature is closely associated with the survival prediction of HCC and is expected to provide new insights into targeted therapy for HCC patients.

Static magnetic field increases aerobic nitrogen removal from hypersaline wastewater in activated sludge with coexistence of fungi and bacteria.

Fungi have been found to exist in activated sludge treating saline wastewater, but their role in removing pollution has been neglected. This study explored the aerobic removal of total inorganic nitrogen (TIN) from saline wastewater under static magnetic fields (SMFs) with several strengths. Compared to the control, the aerobic removal of TIN was significantly increased by 1.47 times in 50 mT SMF, due to the increased dissimilation nitrogen removal by fungi and bacteria. Under SMF, fungal nitrogen dissimilation removal was significantly increased by 3.65 times. The fungal population size decreased, and its community composition changed significantly under SMF. In contrast, bacterial community composition and population remained relatively stable. Under SMFs, heterotrophic nitrification - aerobic denitrification bacteria Paracoccus and the fungi denitrifying Candida formed a synergistic interaction. This study elucidates the fungal role in aerobic TIN removal and provides an efficient solution to improve TIN removal from saline wastewater by SMF.

Design, synthesis, and antitumor activity of novel oleanolic acid analogues targeting EGFR.

Based on the simulated docking of Epidermal growth factor receptor inhibitors with known active small molecule compounds, computer-aided drug design technology was used to analyze key amino acid fragments and determine the active groups binding with key sites. Then, twelve novel analogues of oleanolic acid (OA) were synthesized by introducing active groups at the C-3 and C-28 positions of OA. The structures of these novel analogues were confirmed by NMR and MS. Furthermore, the antitumor activities of these novel analogues were evaluated by MTT assay. As a result, compounds I3 and II3 showed stronger cytotoxicity on tumor cells than positive controls. In conclusion, our study synthesized twelve novel analogues of OA and determined compounds I3 and II3 had better antitumor effect, which may be potential candidate compounds for tumor therapy.

Synthesis and anti-tumor activity of asiatic acid derivatives targeting VEGFR.

To discovery novel VEGFR inhibitors, 12 novel asiatic acid derivatives were designed by computer-aided drug design (CADD) technology. Then, these novel asiatic acid derivatives were synthesized by introducing active groups at ring A and C-28 positions of asiatic acid. The structures of these novel analogues were confirmed by NMR and MS. Moreover, the anti-tumor activities of these novel asiatic acid derivatives on human hepatoma cells HepG2 and human gastric cancer cells SGC7901 were evaluated by MTT assay. As a result, compounds I2 and II4 showed stronger cytotoxicity on tumor cells than asiatic acid and positive control drugs such as gefitinib and paclitaxel. In conclusion, our study synthesized twelve novel asiatic acid derivatives and determined compounds I2 and II4 had better anti-tumor effect which may be potential candidate compounds for tumor therapy.

A halophilic aerobic-heterotrophic strain Halomonas venusta SND-01: Nitrogen removal by ammonium assimilation and heterotrophic nitrification-aerobic denitrification.

Nitrogen (N) removal from high-salinity wastewater is a major challenge. The aerobic-heterotrophic nitrogen removal (AHNR) process has been demonstrated to be feasible for treating hypersaline wastewater. In this study, Halomonas venusta SND-01, a halophilic strain capable of performing AHNR, was isolated from saltern sediment. The strain achieved ammonium, nitrite, and nitrate removal efficiencies of 98%, 81%, and 100%, respectively. The N balance experiment suggests that this isolate removes N mainly via assimilation. Various functional genes related to N metabolism were found in the genome of the strain, establishing a complex AHNR pathway that includes ammonium assimilation, heterotrophic nitrification-aerobic denitrification, and assimilatory nitrate reduction. Four key enzymes in the N removal process were successfully expressed. The strain exhibited high-adaptability under C/N ratios of 5-15, salinities of 2%-10% (m/v), and pH of 6.5-9.5. Therefore, the strain shows high potential for treating saline wastewater with different inorganic N compositions.

A novel Pseudomonas aeruginosa strain performs simultaneous heterotrophic nitrification-aerobic denitrification and aerobic phosphate removal.

Nitrogen and phosphate removal from wastewater relies on different functional bacteria. In this study, a novel strain affiliated with Pseudomonas aeruginosa was isolated from activated sludge by gradient dilution and performed heterotrophic nitrification-aerobic denitrification and aerobic phosphate removal (HNADPR). The strain showed an ammonium removal efficiency of 87% and a phosphate removal efficiency of 97% under optimal conditions, such as C/N ratio of 10, P/N ratio of 0.1, temperature of 30°C, and pH of 7.5-8.5. The modified Gompertz model could fit well the heterotrophic ammonium nitrification, aerobic nitrite/nitrate denitrification, and aerobic phosphate removal processes. Functional gene amplification indicated that ammonium removal followed the complete HN-AD pathway (NH4+ â†’ NH2OH â†’ NO2- â†’ NO3- â†’ NO2- â†’ NO â†’ N2O â†’ N2). Phosphate removal only occurred under aerobic conditions and ceased under anaerobic conditions. In successive aerobic cycles, the strain persistently took up phosphate. In wastewater, phosphate was aerobically converted into cell membrane, intracellular and extracellular polymeric substrates (EPS). Phosphorus in the form of phosphate monoester was pooled in EPS. A hypothetic aerobic phosphate removal model for strain SNDPR-01 is proposed to improve our understanding of the novel bacterial function of HNADPR.

Coupling Magnetic Field and Salinity Upshock To Improve Polyhydroxyalkanoate Productivity by Haloferax mediterranei Feeding on Molasses Wastewater.

Low polyhydroxyalkanoate (PHA) volumetric productivity from wastewater limits low-cost PHA production. To resolve this problem, an external magnetic field (MF) coupled with upshock salinity was applied to PHA production by Haloferax mediterranei (family Halobacteriaceae). Elevating the fermentation salinity over the optimal growth salinity (200 g/L) increased the PHA cell content while inhibiting cell proliferation, decreasing volumetric productivity. When a MF of 50 mT in 300 g/L salinity was applied, H. mediterranei proliferation and PHA cell content were promoted, leading to a 7.95% increase in PHA volumetric productivity in synthetic molasses wastewater and a 13.82% increase in glucose feeding compared with those in 200 g/L salinity. Under the MF, osmotic pressure regulation was activated by accumulating K+ and increasing betaine synthesis. The maximum betaine content increased by 74.33% in 300 g/L salinity with a 50-mT MF compared with that in 200 g/L salinity. When a 50-mT MF in 300 g/L salinity was applied, the malondialdehyde (MDA) content decreased by 32.66% and the activity of superoxide dismutase (SOD) increased by 46.89%, which reduced the oxidative damage. This study provides a new solution to enhance PHA volumetric productivity by MF and an insight into the magnetic effects of H. mediterranei. IMPORTANCE The obstacle to replacing petroplastics with PHA is its high production cost. To increase the fermentation economy, a novel strategy of coupling a MF with salinity upshock was applied, which enhanced the PHA volumetric productivity of H. mediterranei in fermenting molasses wastewater. The magnetic effect of H. mediterranei was found at a MF of 50 mT, which improved the salt tolerance of H. mediterranei and reduced the oxidative damage induced by the elevated salinity, thereby promoting proliferation and PHA cell content. This is the first time a technical method for enhancing PHA volumetric productivity by means of a MF has been proposed. Such a strategy can advance the utilization of H. mediterranei for the industrial production of PHA using organic wastewater.

Effect of sex on the association between arterial partial pressure of oxygen and in-hospital mortality in ICU patients with cardiogenic shock: a retrospective cohort study.

Background: Maintaining tissue perfusion and oxygen supply are essential for cardiogenic shock (CS) treatment. Sex has been reported to be associated with mortality and oxygen use in patients with CS. Males and females respond differently to hypoxia. We designed this cohort study to evaluate the effects of sex on the association between the arterial partial pressure of oxygen (PaO2) and in-hospital mortality. Methods: We used the Medical Information Mart for Intensive Care (MIMIC) IV database for this cohort study. The outcome was in-hospital mortality. The relationship between the PaO2 and in-hospital mortality was compared with sex (via an interaction test) using multivariable Cox regression models. Presence of interaction between PaO2 and sex was tested by using inter interaction terms. Results: A total of 1,772 patients with CS were enrolled in this study. The association between PaO2 and in-hospital mortality appeared to differ between males and females [hazard ratio (HR): 0.997, 95% confidence interval (CI): 0.995-0.999 vs. HR: 1.002, 95% CI: 0.999-1.003, P for interaction =0.002]. We repeated the analyses, based on different PaO2 category (PaO2 <60 mmHg; PaO2 60-100 mmHg; PaO2 >100 mmHg) and the results remained stable, P for interaction =0.008. Conclusions: Sex affects the relationship between PaO2 and in-hospital mortality in CS patients. Our findings may lead to the development of individualized therapies that focus on the use of different target oxygen partial pressures in different sexes to treat patients with CS.

Thermally assisted self-healing behavior of anhydride modified polybenzoxazines based on transesterification.

A self-healing polybenzoxazine is synthesized solely based on dynamic ester bonds. For this purpose, an anhydride (succinic anhydride) was added into bisphenol F derived benzoxazine monomer before thermocuring. Owing to the transesterification of newly formed ester bonds, the thermoset network behaves as a thermoplastic at 140 °C in the presence of Zn (Ac)2, and shows self-healing properties even after multiple damage-healing cycles. Furthermore, kinetics study indicates that the transesterification is a first-order reaction and the activation energy is about 135.4 kJ/mol. This study proposes a facile and economical way to prepare self-healing polybenzoxazine. It has promising applications in coating, adhesive, and other smart materials that rely on structurally dynamic polymers.

N,N'-[2,2'-(Phenyl-aza-nedi-yl)bis-(ethane-2,1-di-yl)]dipicolinamide.

The asymmetric unit of the title compound, C22H23N5O2, contains two independent mol-ecules with similar conformations; the terminal pyridine rings are oriented at dihedral angles of 23.99 (8) and 18.07 (8)° with respect to the central benzene ring in one mol-ecule and 28.99 (8) and 23.22 (8)° in the other. In the crystal, N-H⋯O and weak C-H⋯O hydrogen bonds link the mol-ecules into a three-dimensional supra-molecular structure. Weak inter-molecular C-H⋯π inter-actions are also observed in the crystal.

Characterization of the anti-diabetic and antioxidant effects of rehmannia glutinosa in streptozotocin-induced diabetic Wistar rats.

This study investigated the effects of Rehmannia glutinosa individually as well as in combination with the oral hypoglycemic agent, metformin in streptozotocin (STZ)-induced diabetic Wistar rats. R. glutinosa ethanolic extract was prepared and the constituents were characterized using fractionation by column chromatography, followed by high performance liquid chromatography-mass spectrometry. STZ (65 mg/kg) was injected intraperitoneally to induce diabetes in Wistar rats. The diabetic rats were divided into the following groups (each n = 6) and received the respective treatments for 30 days: (1) metformin (500 mg/kg), (2) R. glutinosa (200 mg/kg), (3) metformin (500 mg/kg) and R. glutinosa (200 mg/kg) and (4) diabetic control (DC). A reduction in plasma glucose levels caused by the herb was not as significant as metformin compared to the diabetic control (p < 0.05). However, R. glutinosa-treated group showed reductions in plasma C-reactive protein (CRP) levels compared to the diabetic controls (p < 0.05) as well as metformin-treated group (p < 0.05). An enhanced reduction in CRP concentration was observed in the group receiving both herb and metformin compared to metformin-treated group (p < 0.05). Reduction in CRP levels suggests an anti-inflammatory activity of the herb.