ObjectiveAt present, the most commonly used photosensitizers in photodynamic therapy are still chemical photosensitizers, such as porphyrin and methylene blue, in order to specifically target cellular tissues, and thus poison cells, chemical photosensitizers need to use antibody conjugation or a transgenically encoded tag with affinity for the modified photosensitizing ligand, e.g. FlAsH, ReAsh or Halo Tag. Gene-encoded photosensitizers can directly poison cells by targeting specific cell compartments or organelles. However, currently developed gene-encoded photosensitizers have low reactive oxygen species production and low cytotoxicity, so it is necessary to continue to develop and obtain photosensitizers with higher reactive oxygen species production for the treatment of microbial infections and tumors. MethodsIn this study, we developed a photosensitizer LovPSO2 based on the light-oxygen-voltage (LOV) structural domain of phototropin-1B-like from Oryza sativa japonica. LovPSO2 was expressed in E. coli BL21(DE3) and purified to obtain protein samples, the purified protein samples were added 3 µmol/L singlet oxygen probe of SOSG and 5 µmol/L superoxide anion probe of DHE after fixed to A₄₄₅=0.063±0.003, respectively, then measured every 2 min of singlet oxygen production for 10 min and every 1 min of superoxide anion production for 5 min under blue light irradiation at 445 nm, 70 µmol·m^-2·s^-1. ResultsThe results showed that LovPSO2 could produce a large amount of singlet oxygen under blue light irradiation at 445 nm, 70 µmol·m^-2·s^-1, and its singlet oxygen quantum yield was 0.61, but its superoxide anion yield was low, so in order to improve the superoxide anion yield of LovPSO2, a mutant with a relatively high superoxide anion yield was obtained by further development and design on its basis LovPRO2. The stability of proteins is crucial for research in drug development and drug delivery, among others. Temperature and light are the key factors affecting the production of reactive oxygen species (ROS) by photosensitive proteins and their stability, while the temperature in cell culture and mammals in vivo is about 37°C, and the temperature inside tumor cells is about 42-45°C. Therefore, we further analyzed the photostability of miniSOG, SOPP3, LovPSO2, and LovPRO2 and their thermostability at 37℃ and 45℃. The analysis of proteins thermostability showed that LovPSO2 and LovPRO2 had better thermostability at 37℃ and 45℃, respectively. Analysis of the photostability of the proteins showed that LovPRO2 had better photostability. In addition, to further determine the phototoxic effects of photosensitizers, LovPSO2 and LovPRO2 were expressed in E. coli BL21(DE3) and HeLa cells, respectively. The results showed that LovPSO2 and LovPRO2 had better phototoxicity to E. coli BL21(DE3) under blue light irradiation, and the cellular phototoxicity lethality was as high as 90% after 30 min of continuous light irradiation, but the phototoxicity was weaker in HeLa cells. The reason for this result may be that the intracellular environment exacerbated the photobleaching of FMN encapsulated by LovPSO2 and LovPRO2, respectively, which attenuated the damage of reactive oxygen species to animal cellular tissues, limiting its use as a mechanistic tool to study oxidative stress. ConclusionLovPSO2 and LovPRO2 can be used as antibacterial photosensitizers, which have broader application prospects in the food and medical fields.

Objective: To evaluate and compare the accuracy of body mass index (BMI), waist circumference (WC), waistcorrected BMI (wBMI), and waist to height ratio (WHtR) in predicting hand grip strength (HGS) in high school girls, so as to provide the reference for evaluating their overall physical fitness and health status. Methods: From May to December in 2022, a total of 1 600 girls aged 15 to 18 years old were selected by cluster random sampling from 12 high schools in Xuzhou, Jiangsu Province. Measures of HGS, waist circumference, height and weight among high school girls were taken, and their BMI, wBMI and WHtR were calculated. Pearson correlation analysis and Logistic regression were used to analyze the association between BMI, wBMI, WC, WHtR and HGS Receiver operating characteristic (ROC) curves were constructed to evaluate the accuracy of different indicators in predicting HGS Results: Pearson correlation analysis showed that the BMI, wBMI, WHtR and HGS expression of high school girls were positively correlated ( r =0.31, 0.27, 0.32, 0.14, P < 0.01 ). Logistic regression analysis showed that BMI, WC and wBMI were correlated with HGS expression ( OR=2.00, 0.47, 1.22, P <0.05), while the association of WHtR and HGS expression had no statistical significance ( OR=0.51, P >0.05). The area under the curve (AUC) of BMI for predicting HGS expression in high school girls was the largest (AUC=0.65, 95% CI =0.61-0.69), followed by the AUC of wBMI for predicting HGS expression (AUC=0.65, 95% CI =0.57-0.66)( P <0.05). The most sensitivity was wBMI (71.5%), followed by BMI (69.4%), and the least sensitivity was WHtR (52.3%); and WC had the best specificity (61.1%), whereas wBMI had a relatively low specificity (52.5%). Conclusion For high school girls, BMI, WC and wBMI could predict the strenth of HGS expression, but BMI and wBMI have the highest accuracy and sensitivity, while wBMI has the lowest specificity in predicting the strenth of HGS.

Objective To establish a method for acquisition, perfusion, preservation and transportation of the genetically modified pig kidneys. Methods An eight genetically modified pig was utilized as experimental subject. Prior to kidneys procurement, the health status of the pig was assessed through hematology examination, and the vascular structure of the kidneys was examined using imaging techniques. Following kidneys acquisition, the pig kidneys were perfused and subsequently packaged into the cryogenic storage container labeled "For Organ Transportation Only" for interprovincial transport after communicating the transportation process with transportation department. To evaluate pathological damage to the pig kidneys, a serious of methods were employed such as hematoxylin-eosin (HE) staining, real-time fluorescent quantitative polymerase chain reaction (RT-qPCR), terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) fluorescence staining and enzyme-linked immune absorbent assay (ELISA). Results The preoperative examination of the eight genetically modified pig showed that the serum creatinine was 73.2 μmol/L, blood urea nitrogen was 2.8 mmol/L and hemoglobin was 116 g/L, all within the normal range, indicating normal renal function. CT angiography revealed no lesions in the pig kidneys, and no dilation, stenosis or premature branching of the blood vessels. The total time of obtaining the left and right kidneys from the eight genetically modified pig was (125 ± 10) min, with a blood loss of (20 ± 2) mL. The warm ischemia times were 3 min and 7 min, respectively. The perfusion and trimming times of the left and right kidneys were 36 min and 41 min, respectively. After perfusion, both kidneys were white and moist. The cold preservation and transportation time was 8 h. HE staining showed that some glomeruli were shrunk, and the lumens of the surrounding renal tubules were slightly depressed and swollen with partial inner membrane shedding and microvacuoles formed when the kidneys were preserved for 8 h. The level of cysteinyl aspartate-specific proteinase-3 messenger RNA in the kidneys tissue gradually increased with the extension of cold preservation time after 2 h (P<0.05). TUNEL fluorescence staining showed that only a small number of cells underwent apoptosis after 8 h of cold preservation, which was not significantly different from that at 0 h (P>0.05). ELISA results showed that the contents of lactate dehydrogenase (LDH) and creatinine in the preservation solution remained relatively stable, but the content of kidney injury molecule 1 (KIM-1) gradually increased with the extension of preservation time, suggesting that the pig kidneys had mild injury. Conclusions By establishing methods for acquisition, perfusion, preservation and transportation of the kidneys from genetically modified donor pig, it is possible to effectively and reliably use genetically modified pig kidneys for xenotransplantation.

Objective To evaluate the survival outcomes of segmentectomy versus lobectomy for T1c non-small cell lung cancer (NSCLC). Methods We searched PubMed, EMbase, Cochrane Central Register of Controlled Trials (CENTRAL), CNKI (China National Knowledge Infrastructure), and Wanfang Data, with the search time limit set from the inception of the databases to February 2024. Three researchers independently screened the literature, extracted relevant information, and evaluated the risk of bias of the included literature according to the Newcastle-Ottawa Scale (NOS). Meta-analysis was conducted using STATA 15.1. Results A total of 8 retrospective cohort studies were included, involving 7 433 patients. The NOS scores of the included studies were all ≥7 points. Patients who underwent lobectomy had significantly higher five-year overall survival (OS) rates compared to those who underwent segmentectomy (adjusted HR=1.11, 95%CI 0.99-1.24, P=0.042). Compared with lobectomy, segmentectomy showed no significant difference in adjusted three-year OS rate (adjusted HR=0.88, 95%CI 0.62-1.24) and adjusted five-year lung cancer-specific survival (adjusted HR=1.10, 95%CI 0.80-1.51, P=0.556) of patients with T1c NSCLC. Moreover, there were no differences in the five-year adjusted relapse-free survival (adjusted HR=1.23, 95%CI 0.82-1.85, P=0.319), and adverse events (OR=0.57, 95%CI 0.37-0.90, P=0.015) in the segmentectomy group were significantly less than those in the lobectomy group. Subgroup analysis based on whether patients received neoadjuvant therapy showed that among studies that excluded patients who received neoadjuvant therapy, no significant difference in 5-year adjusted OS rate was observed between the segmentectomy group and lobectomy group (adjusted HR=1.02, 95%CI 0.81-1.28, P=0.870). Conclusion Segmentectomy and lobectomy show no significant difference in long-term survival in stage T1c NSCLC patients, with segmentectomy associated with fewer postoperative complications. Further high-quality research is needed to confirm the comparative efficacy and safety of lobectomy and segmentectomy for T1c NSCLC patients.

Objective To evaluate the value of an optimized three-dimensional inversion-recovery with real reconstruction (3D-real IR) sequence with a longer repetition time (TR, 16 000 ms) based on modulated flip angle technique in refocused imaging with extended echo train (MATRIX) in the endolymphatic hydrops (EH) imaging after intratympanic gadolinium (Gd) administration, and to compare it with a conventional 3D-real IR based on the turbo spin echo (TSE) sequence. Methods From July 2021 to November 2022, twenty-seven patients received both the conventional and optimized 3D-real IR sequences after bilateral intratympanic Gd administration. Images of the two sequences were qualitativly evaluated and compared. Contrast-to-noise ratio (CNR), signal-to-noise ratio (SNR), and area ratio of endolymph against the total lymphatic space from the two sequences were measured and compared. Results 14(25.9%) ears with insufficient contrast for the EH diagnosis on the conventional sequence were clearly displayed on the optimized sequence. Image score, CNR and SNR of the optimized sequence were significantly higher than those of the conventional sequence (P ＜ 0.001). The scanning time of two sequences was similar. The area ratio of endolymph against the total lymphatic space in the cochlear was significantly higher on the conventional 3D-real IR than that on the optimized 3D-real IR (P ＜ 0.001); there was no statistical difference in the vestibule between the two sequences. Conclusions Compared with conventional sequence, optimized 3D-real IR sequence with a longer TR may be better for evaluation of EH after intratympanic Gd administration.

Objective To investigate the value of artificial intelligence-assisted compressed sensing (ACS) technology for intravenous gadolinium contrast-enhanced magnetic resonance imaging of the inner ear using three-dimensional fluid-attenuated inversion recovery (3D-FLAIR) sequence. Methods The patients received gadolinium contrast-enhanced magnetic resonance imaging using ACS and united compressed sensing (uCS) 3D-FLAIR at Zhongshan Hospital, Fudan University from January to November 2024 were prospectively enrolled. The repetition time was 16 000 ms, and acquisition time was 6 min 40 s and 10 min 24 s in ACS 3D-FLAIR and uCS 3D-FLAIR, respectively. The images on the two sequences were evaluated independently by two radiologists. The image quality of the two sequences was subjectively evaluated and compared. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were compared between the two sequences. The grading consistencies using two sequences and between the two doctors were analyzed. Results There was no statistically difference in subjective score of image quality between the two sequences. SNR and CNR of the ACS 3D-FLAIR sequence were significantly higher than those of the uCS 3D-FLAIR sequence (P＜0.001). The kappa values of grades of cochlear and vestibular endolymphatic hydrops were 0.942 and 0.888 using two sequences (P＜0.001). The kappa values of grades of cochlear and vestibular endolymphatic hydrops using the ACS 3D-FLAIR sequence between the two doctors were 0.784 and 0.831, respectively (P＜0.001); the kappa values of grades of cochlear and vestibular endolymphatic hydrops using uCS 3D-FLAIR sequence between the two doctors were 0.725 and 0.756, respectively (P＜0.001). Conclusions ACS 3D-FLAIR could provide higher SNR and CNR than uCS 3D-FLAIR, and is more suitable for intravenous gadolinium contrast-enhanced magnetic resonance imaging of the inner ear; the endolymphatic hydrops grades using ACS 3D-FLAIR is similar to use uCS 3D-FLAIR.

Circadian rhythm is an endogenous biological clock mechanism that enables organisms to adapt to the earth’s alternation of day and night. It plays a fundamental role in regulating physiological functions and behavioral patterns, such as sleep, feeding, hormone levels and body temperature. By aligning these processes with environmental changes, circadian rhythm plays a pivotal role in maintaining homeostasis and promoting optimal health. However, modern lifestyles, characterized by irregular work schedules and pervasive exposure to artificial light, have disrupted these rhythms for many individuals. Such disruptions have been linked to a variety of health problems, including sleep disorders, metabolic syndromes, cardiovascular diseases, and immune dysfunction, underscoring the critical role of circadian rhythm in human health. Among the numerous systems influenced by circadian rhythm, the skin—a multifunctional organ and the largest by surface area—is particularly noteworthy. As the body’s first line of defense against environmental insults such as UV radiation, pollutants, and pathogens, the skin is highly affected by changes in circadian rhythm. Circadian rhythm regulates multiple skin-related processes, including cyclic changes in cell proliferation, differentiation, and apoptosis, as well as DNA repair mechanisms and antioxidant defenses. For instance, studies have shown that keratinocyte proliferation peaks during the night, coinciding with reduced environmental stress, while DNA repair mechanisms are most active during the day to counteract UV-induced damage. This temporal coordination highlights the critical role of circadian rhythms in preserving skin integrity and function. Beyond maintaining homeostasis, circadian rhythm is also pivotal in the skin’s repair and regeneration processes following injury. Skin regeneration is a complex, multi-stage process involving hemostasis, inflammation, proliferation, and remodeling, all of which are influenced by circadian regulation. Key cellular activities, such as fibroblast migration, keratinocyte activation, and extracellular matrix remodeling, are modulated by the circadian clock, ensuring that repair processes occur with optimal efficiency. Additionally, circadian rhythm regulates the secretion of cytokines and growth factors, which are critical for coordinating cellular communication and orchestrating tissue regeneration. Disruptions to these rhythms can impair the repair process, leading to delayed wound healing, increased scarring, or chronic inflammatory conditions. The aim of this review is to synthesize recent information on the interactions between circadian rhythms and skin physiology, with a particular focus on skin tissue repair and regeneration. Molecular mechanisms of circadian regulation in skin cells, including the role of core clock genes such as Clock, Bmal1, Per and Cry. These genes control the expression of downstream effectors involved in cell cycle regulation, DNA repair, oxidative stress response and inflammatory pathways. By understanding how these mechanisms operate in healthy and diseased states, we can discover new insights into the temporal dynamics of skin regeneration. In addition, by exploring the therapeutic potential of circadian biology in enhancing skin repair and regeneration, strategies such as topical medications that can be applied in a time-limited manner, phototherapy that is synchronized with circadian rhythms, and pharmacological modulation of clock genes are expected to optimize clinical outcomes. Interventions based on the skin’s natural rhythms can provide a personalized and efficient approach to promote skin regeneration and recovery. This review not only introduces the important role of circadian rhythms in skin biology, but also provides a new idea for future innovative therapies and regenerative medicine based on circadian rhythms.