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Hemoporfin mediated photodynamic therapy(HMME-PDT) has been proved safe and effective for treating PWS in both adults and children in previous articles, especially for lager segment lesions. However, crusts and scars associated with HMME-PDT cannot be ignored. The article briefly summarized several post-treatment reactions after HMME-PDT treatment relative to prognosis, and emphasized that early identification and intervention the post-treatment reactions after HMME-PDT, which has very important significance to prognosis.

Ulcerative colitis (UC) is characterized by increased cell death in intestinal epithelial cell (IEC), which compromises gut barrier function and activates inflammation. Aberrant mitochondrial dynamics have been implicated in various forms of cell death, but it is currently unclear if they play a role in IEC death and colitis pathogenesis. This study aims to investigate the contribution of aberrant mitochondrial dynamics to colitis progression using cellular models, animal models, and clinical samples. The results revealed that IEC in mice with Dextran sulfate sodium salt (DSS)-induced colitis exhibited dynamin-related protein 1 (Drp1)-mediated mitochondrial fission and Z-DNA binding protein 1 (ZBP1)-dependent PANoptosis, which is a combination of apoptosis, necroptosis, and pyroptosis. However, these processes and the pathogenesis of DSS-induced colitis were significantly attenuated in IEC-specific Drp1 heterozygous knockout mice. Importantly, ZBP1-PANoptosis and Drp1-mediated mitochondrial fission were observed in IEC of UC patients, exhibiting a positive correlation with disease severity. Mechanistically, hyperactivated mitochondrial fission induced mitochondrial reactive oxygen species production leading to PANoptosis through ZBP1 sulfenylation at Cys327 independently of its Zα domain. Saquinavir, an FDA-approved drug identified through in-silico screening alongside in vivo and in vitro experiments, inhibits mitochondrial fission thereby enhancing therapeutic efficacy in mice with colitis.

Macrophage-based cell therapeutics is an emerging modality to treat cancer and repair tissue damage. A reproducible manufacturing and engineering process is central to fulfilling their therapeutic potential. Here, we establish a robust macrophage-manufacturing platform (Mo-Mac) and demonstrate that macrophage functionality can be enhanced by N1-methylpseudouridine (m1Ψ)-modified mRNA. Using single-cell transcriptomic analysis as an unbiased approach, we found that >90% cells in the final product were macrophages while the rest primarily comprised T cells, B cells, natural killer cells, promyelocytes, promonocytes, and hematopoietic stem cells. This analysis also guided the development of flow-cytometry strategies to assess cell compositions in the manufactured product to meet requirements by the National Medical Products Administration. To modulate macrophage functionality, as an illustrative example we examined whether the engulfment capability of macrophages could be enhanced by mRNA technology. We found that efferocytosis was increased in vitro when macrophages were electroporated with m1Ψ-modified mRNA encoding CD300LF (CD300LF-mRNA-macrophage). Consistently, in a mouse model of acute liver failure, CD300LF-mRNA-macrophages facilitated organ recovery from acetaminophen-induced hepatotoxicity. These results demonstrate a GMP-compliant macrophage-manufacturing process and indicate that macrophages can be engineered by versatile mRNA technology to achieve therapeutic goals.

In this study, a large size Ti-0.3Mo-0.8Ni (TA10) alloy ingot melted by electron beam cold hearth melting (EBCHM) technology was investigated. The microstructure, mechanical properties, and corrosion behavior of as-cast, hot-rolled, and annealed TA10 alloys were investigated. The results show that different states of TA10 alloys have different microstructure and properties. The microstructure of the as-cast TA10 alloy exhibits the Widmanstätten α phase, and the hot-rolled TA10 sheet shows a fibrous structure with an obvious rolling streamline. After 650 °C annealing, the intergranular β phase decreases, and most of the strip α phase changes to the equiaxed α phase. With the annealing temperature increasing to 840 °C, the microstructure gradually changed from an equiaxed structure to a duplex structure. The mechanical properties of the TA10 alloy were enhanced after hot-rolling with an increase in ultimate tensile strength from 386.5 MPa to 610 MPa. Additionally, the elongation increased from 15.6 % to 23.3 %. Upon annealing at varying temperatures, it was observed that the strength decreased, reaching to 423.5 MPa at 650 °C and 478.2 MPa at 840 °C, while the plasticity increased significantly, reaching to 26.5 % at 650 °C and 28.6 % at 840 °C. The improved strength was attributed to the better grain boundary slip of the equiaxed structure. The corrosion resistance of titanium alloys is closely connected with their microstructure. The results of the immersion corrosion test indicate that the samples in various states exhibit similar corrosion behavior. Additionally, the hot-rolled TA10 alloy shows the highest corrosion resistance, with a lower corrosion rate of 0.34459 mm/year. The as-cast TA10 alloy shows the lowest corrosion resistance, with a lower corrosion rate of 1.37559 mm/year.

Studies have shown that consuming aquatic products is the primary pathway for human uptake of polybrominated diphenyl ethers (PBDEs). This study collected seven types of aquatic products eaten in Guangzhou City. Gas chromatography‒mass spectrometry (GC/MS) was used to investigate eight PBDE congeners to analyze their concentration, distribution, and potential risk. The concentration of PBDEs in aquatic products ranged from 1.92 to 91.11 ng/g lw, with BDE–209, BDE–99, and BDE–154 as the predominant PBDE congeners. Moreover, the concentrations and congener profiles of these contaminants vary in aquatic products. The highest accumulation level was found in shrimp and clams, primarily attributed to dietary habits, metabolic capacity, and accumulation of xenobiotics. According to the dietary questionnaire, the total consumption of aquatic animals was 82.64 g/day, with a significant non-carcinogenic risk to consumers in Guangzhou at higher levels of consumption (HI ≥ 1). Therefore, the maximum allowable daily consumption of grass carp, crucian carp, tilapia, Japanese seaperch, shrimp, clam and crab is 33.33, 55.00, 67.50, 44.44, 41.67, and 51.67 g/day, corresponding to daily intake frequencies of 5, 8, 10, 6, 6, 7, and 5 times/month, respectively. Our results could provide reasonable dietary advice for humans.

The modular multilevel converter (MMC) topology is recognized as the most viable technology option applied in high-voltage and high-power transmission systems. In this paper, the virtual capacitance based control for MMC-HVDC (MMC-High Voltage Direct Current) systems is proposed to increase the frequency support ability and enhance the system stability when the receiving-end ac grid is weak. The auxiliary control derived from the dynamic energy balance equation with the introduced virtual capacitance for the arm current control of MMC is used as the additional control degree of freedom to enhance the response of ac system frequency. With the proposed control, the MMC can simulate a virtual capacitor with adjustable and larger capacitance capacity value to help increase the dynamic response of ac frequency. Finally, a benchmark two-terminal MMC-HVDC simulation model is established on PSCAD/EMTDC to verify the validity of the proposed control.

Microbeads used in personal care products have been one of the important sources of microplastics (MPs), and little has been reported on their environmental behaviors and health risks. The characteristics of environmentally persistent free radicals (EPFRs) and the toxicity assessment of MPs (environmentally relevant concentrations) from cosmetics during photoaging remains largely unknown. In this study, the formation of EPFRs on polyethylene (PE) microbeads from facial scrubs under light irradiation and their toxicity were investigated using C. elegans as a model organism. The results suggested that light irradiation induced the generation of EPFRs, which accelerates the aging process and alters the physicochemical properties of PE microbeads. Acute exposure to PE (1 mg/L) at photoaged times of 45–60 d significantly decreased the physiological indicators (e.g., head thrashes, body bends, and brood size). The oxidative stress response and stress-related gene expression were also enhanced in nematodes. The addition of N-acetyl-l-cysteine induced significant inhibition of toxicity and oxidative stress in nematodes exposed to 45–60 d of photoaged PE. The Pearson correlation results showed that the concentration of EPFRs was significantly correlated with physiological indicators, oxidative stress, and related-genes expression in nematodes. The data confirmed that the generation of EPFRs combined with heavy metals and organics contributed to toxicity induced by photoaged PE, and oxidative stress might be involved in regulating adverse effects in C. elegans. The study provides new insight into the potential risks of microbeads released into the environment during photoaging. The findings also highlight the necessity for considering the role of EPFRs formation in evaluating the impacts of microbeads.

Summary: Testicular germ cell tumors and closely related embryonal stem cells are exquisitely sensitive to cisplatin, a feature thought to be linked to their pluripotent state and p53 status. It remains unclear whether and how cellular state is coordinated with p53 to confer cisplatin sensitivity. Here, we report that positive transcription elongation factor b (P-TEFb) determines cell fate upon DNA damage. We find that cisplatin rapidly activates P-TEFb by releasing it from inhibitory 7SK small nuclear ribonucleoprotein complex. P-TEFb directly phosphorylates pluripotency factor estrogen-related receptor beta (ESRRB), and induces its proteasomal degradation to enhance pro-survival glycolysis. On the other hand, P-TEFb is required for the transcription of a substantial portion of p53 target genes, triggering cell death during prolonged cisplatin treatment. These results reveal previously underappreciated roles of P-TEFb to coordinate the DNA damage response. We discuss the implications for using P-TEFb inhibitors to treat cancer and ameliorate cisplatin-induced ototoxicity.

To investigate the characteristics of heavy metals (As, Cd, Cr, Cu, Pb, Hg, Ni and Zn) in urban road dust from different cities and functional areas in the Pearl River Delta (PRD), South China, a total of 294 dust samples were analyzed. The contamination characteristics and health risk of heavy metals in the dust were assessed, their chemical speciation were distinguished, and their sources were identified by the correlations, cluster and principal component analysis (PCA). The mean concentrations of As (15.89 mg/kg), Cd (1.59 mg/kg), Cr (143.75 mg/kg), Cu (184.42 mg/kg), Pb (114.82 mg/kg), Hg (0.11 mg/kg), Ni (41.53 mg/kg) and Zn (645.94 mg/kg) in urban road dust were in high or moderate levels compare with other previous researches. In this case, the contamination of Cr, Cu, Ni and Zn in the industrial area (IA) and the contamination of Cd and Hg in the commercial area (CA) were significantly higher relative to other functional areas (P

Summary: Taxane-based reagents, such as Taxol, Taxotere, and Abraxane, are popular anti-cancer drugs that can differ in their clinical efficacy. This difference is generally attributed to their active pharmaceutical ingredients. Here, we report a serendipitous discovery that Taxol induces metabolic dysregulation and unfolded protein response. Surprisingly, these effects of Taxol are entirely dependent on its excipient, Cremophor EL (CrEL). We show that CrEL promotes aerobic glycolysis and in turn results in drastic upregulation of angiopoietin like 4 (ANGPTL4), a major regulator of human blood lipid profile. Notably, premedication with dexamethasone further enhances the expression of ANGPTL4. Consistently, we find that the amplitude and frequency of increase in triglycerides is more prominent in Taxol-treated patients with breast cancer. In addition, we find that CrEL activates the unfolded protein response pathway to trigger proinflammatory gene expression and caspase/gasdermin E-dependent pyroptosis. Finally, we discuss the implications of these results in anti-cancer therapies.

As the secondary metabolites of cyanobacterial harmful algal blooms (Cyano-HABs), microcystins (MCs) were generated under various environmental and cellular conditions. The understanding of the causes of MCs generation is of great interest in the field of water treatment and environmental science. In this work, we studied how Microcystis aeruginosa (FACHB-905) cell densities affect the MCs synthetase genes (mcy) expression, microcystin-LR (MC-LR) and quorum sensing molecules (Acyl-homoserine lactones (AHLs)) production. An electrochemical sensor was developed here for sensitive and quantitative detection of MC-LR that cultured at different cell densities. The results showed that mcy expression and MC-LR concentration started to increase when the cell density reached ca. 22 × 106 cells/mL, and was significantly increased with increasing cell densities. Moreover, the up-regulation of AHLs with increasing cell densities revealed that MC-LR is quorum sensing-mediated. Our results undoubtedly confirmed that MC-LR was produced in a cell density-dependent way that mimics quorum sensing, and the minimum cell density (ca. 22 × 106 cells/mL) that was required to produce MC-LR was provided and offered a reference standard for the prevention and control of MCs pollution in the actual water environment.