This study identified six novel azaphilones, isochromophilones G-L (1-6), and three novel biosynthetically related congeners (7-9) from Diaporthe sp. SCSIO 41011. The structures and absolute configurations were elucidated through comprehensive spectroscopic analyses combined with experimental and calculated electronic circular dichroism (ECD) spectra. Significantly, three highly oxygenated azaphilones contain an acetyl group at the terminal chain (4) or linear conjugated polyenoid moieties (5 and 6), which occur infrequently in the azaphilone family. Additionally, several compounds demonstrated inhibition of lipopolysaccharide (LPS)-induced nuclear factor kappa-B (NF-κB) activation in RAW 264.7 macrophages at 20 μmol·L^-1. The novel compound (1) effectively inhibited receptor activator of NF-κB ligand (RANKL)-induced osteoclast differentiation without exhibiting cytotoxicity in bone marrow and RAW 264.7 macrophages, indicating its potential as a promising lead compound for osteolytic disease treatment. This research presents the first documented evidence of azaphilone derivatives as inhibitors of RANKL-induced osteoclastogenesis.
Animals ; Mice ; RANK Ligand/genetics* ; RAW 264.7 Cells ; Osteoclasts/metabolism* ; Benzopyrans/isolation & purification* ; Osteogenesis/drug effects* ; Macrophages/metabolism* ; Molecular Structure ; Pigments, Biological/isolation & purification* ; Ascomycota/chemistry* ; NF-kappa B/genetics* ; Cell Differentiation/drug effects*

Objective:To explore the associations of temperature, relative humidity, and their interaction effect with fall risk.Methods:Data on fall cases were collected using the national injury surveillance system from May to September, in 2006-2022 in Hubei Province. Combined with the meteorological and air pollution data, we conducted a time-stratified case-crossover design and used conditional logistic regression models and distributed lag nonlinear models to examine the exposure-response relationships between temperature, humidity, and fall risk. We further divided the low and the high temperature groups and the low and the high relative humidity groups and analyzed the excess risk ( ER) of falls attributed to dry-hot or wet-hot events. Finally, we calculated the additive interactions of temperature and humidity on fall risk. Results:A total of 55 401 fall cases were included. With the increase in temperature and relative humidity decrease, the exposure-response curves of fall showed nonlinear upward trends among all populations. Gender and age differences were found in temperature-fall and relative humidity-fall risk relationships. Compared with wet-non-hot (normal temperature and high relative humidity) events, the ER of fall in dry-hot (high temperature and low relative humidity) events was 14.80% (95% CI: 9.69%- 20.15%), and the ER of wet-hot (high temperature and high relative humidity) events was 9.59% (95% CI: 2.52%-17.13%). However, there was no statistically significant difference between dry-hot and wet-hot events in the fall, and no statistically significant difference between different genders, ages, occupations, and fall occurred place (all P>0.05). No significant synergistic additive interaction was found between temperature and relative humidity on fall risk (relative excess risk due to interaction=-0.08, 95% CI: -0.19-0.02). Conclusions:Higher temperatures and lower relative humidity were associated with increased fall risk. Both dry-hot and wet-hot events had a higher risk of fall, while high temperature and low humidity have no synergistic effect on fall risk.

Objective The purpose of writing the"expert consensus on humanistic care for patients in hospice care"(hereinafter referred to as the"consensus")aims to standardize the practice of humanistic care in the field of hospice care,ensuring that humanistic care is integrated throughout the entire service process for hospice care patients and their families.Methods A systematic search was conducted in domestic and foreign databases for literature related to hospice care and humanistic care,including guidelines,expert consensuses,systematic reviews or Meta-analyses,and evidence summaries.High-quality evidence was evaluated,extracted,and summarized to form the initial draft of the"consensus".From June to October 2024,20 experts from the fields of hospice care,nursing humanities,and evidence-based nursing were invited to participate in 1 round of expert consultation.Among them,13 experts were selected for 2 rounds of expert demonstration meetings.After collating and analyzing the experts' opinions,the initial draft was revised and refined,ultimately resulting in the final version of the"consensus".Results The effective response rate of the consultation questionnaire was 100％,with expert authority coefficient of 0.880,judgment coefficient of 0.935,and familiarity level of 0.825.The Kendall harmony coefficient of the expert consultation was 0.134(P＜0.05).The"consensus"consisted of 13 aspects,including the targets and objectives,principles,institutional guarantees,environmental requirements,etc.Conclusion This"consensus"possesses strong scientific rigor and practicality,which can provide guidance and references for the practice of humanistic care in the field of hospice care,promoting the standardization and humanization of hospice care services.

Mussel adhesive protein (MAP) is increasingly utilized in the biomedical field for the development of various bio-inspired products such as adhesives, protective films, and coatings with diverse properties, owing to its excellent biocompatibility, low immunogenicity, broad-spectrum adhesiveness, and biodegradability. The biological effects and mechanisms of MAP include adhesive film formation, cell migration and proliferation, anti-inflammatory and antioxidant activities, and inhibition of pigment formation. In dermatological applications, MAP demonstrates a significant potential in antibacterial and antipruritic effects, wound healing, barrier repair, and scar regeneration. In recent years, advances in understanding the secretion, distribution, and adhesion mechanisms of MAP, along with innovations in extraction methods, have led to the development of various natural MAP, recombinant MAP, mussel-inspired, and mussel-mimetic biomedical products. However, the biosafety, tissue compatibility, and functionality of these products remain subjects of debate. Further investigation is needed to elucidate the interactions between MAP-based products and various organ tissues and cells within complex biological systems, as well as to thoroughly evaluate their safety and efficacy. Such efforts are essential to achieve high-value utilization of MAP and to explore broader application prospects. Future research may focus on integrating MAP with emerging technologies such as nanotechnology and smart materials to further develop its multifunctional applications in the field of dermatology.

Objective To analyze changes in sleep,mood state,and brain function in healthy populations living in near-sea-level environments before and after exposure to high-altitude environment,and to explore the correlations between regional brain functional changes and variations in sleep and mood states.Methods A total of 45 healthy volunteers were enrolled.The participants came from regions of near-sea-level altitudes and were exposed to the high-altitude environment for a short period of time.The Pittsburgh Sleep Quality Index(PSQI),Zung Self-Rating Depression Scale(SDS),Patient Health Questionnaire-9(PHQ-9),Zung Self-Rating Anxiety Scale(SAS),and Generalized Anxiety Disorder-7(GAD-7)were administered to assess sleep quality as well as depressive and anxiety symptoms at 4 time points—prior to high-altitude exposure,immediately after exposure,one month after returning to low-altitude regions,and three months after returning to low-altitude regions.Resting-state functional magnetic resonance imaging(rs-fMRI)data were collected before and after high-altitude exposure,and regional brain functional parameters,including the amplitude of low-frequency fluctuations(ALFF)and functional connectivity strength,were analyzed.Statistical analyses were performed,including a linear mixed-effects model to evaluate longitudinal changes in scale scores,paired-sample t-tests to compare brain function differences before and after exposure,and Pearson correlation analyses to examine the relationship between brain functional changes and alterations in sleep and mood states.Results Compared with the pre-exposure findings,the participants exhibited significantly increased PSQI scores(8.89±4.41 vs.5.08±2.69,P<0.05)and PHQ-9 scores(3.60±4.19 vs.1.54±2.30,P<0.05)immediately after high-altitude exposure.One month after returning to the low-altitude environment,both sleep and depression scores decreased relative to the findings immediately after exposure(PSQI:3.88±2.13 vs.8.89±4.41,P<0.05;PHQ-9:1.50±2.25 vs.3.60±4.19,P<0.05)and showed no statistically significant difference compared with the pre-exposure findings(P>0.05).Three months after returning to near-sea-level environment,sleep,depression,and anxiety scores were all reduced compared with the findings immediately after exposure(PSQI:3.76±2.31 vs.8.89±4.41,P<0.05;PHQ-9:1.24±2.13 vs.3.60±4.19,P<0.05;SAS:23.84±5.93 vs.27.93±7.05,P<0.05),also showing no significant difference compared with the pre-exposure levels(P>0.05).Brain function analysis revealed that,relative to the pre-exposure levels,ALFF in the bilateral superior temporal gyrus,insula,and dorsolateral prefrontal cortex(DLPFC)increased after high-altitude exposure(P<0.05),and that functional connectivity strength in the DLPFC was also elevated(P<0.05).Furthermore,changes in DLPFC functional connectivity strength were positively correlated with changes in sleep and mood scores(P<0.05).Conclusion High-altitude exposure has a significant impact on the sleep,mood states,and brain function of populations from near-sea-level regions,and DLPFC,in particular,is closely associated with changes in sleep and mood states.The findings of this study provide a theoretical basis for health management and intervention strategies in high-altitude environments.

Objective The purpose of writing the"expert consensus on humanistic care for patients in hospice care"(hereinafter referred to as the"consensus")aims to standardize the practice of humanistic care in the field of hospice care,ensuring that humanistic care is integrated throughout the entire service process for hospice care patients and their families.Methods A systematic search was conducted in domestic and foreign databases for literature related to hospice care and humanistic care,including guidelines,expert consensuses,systematic reviews or Meta-analyses,and evidence summaries.High-quality evidence was evaluated,extracted,and summarized to form the initial draft of the"consensus".From June to October 2024,20 experts from the fields of hospice care,nursing humanities,and evidence-based nursing were invited to participate in 1 round of expert consultation.Among them,13 experts were selected for 2 rounds of expert demonstration meetings.After collating and analyzing the experts' opinions,the initial draft was revised and refined,ultimately resulting in the final version of the"consensus".Results The effective response rate of the consultation questionnaire was 100％,with expert authority coefficient of 0.880,judgment coefficient of 0.935,and familiarity level of 0.825.The Kendall harmony coefficient of the expert consultation was 0.134(P＜0.05).The"consensus"consisted of 13 aspects,including the targets and objectives,principles,institutional guarantees,environmental requirements,etc.Conclusion This"consensus"possesses strong scientific rigor and practicality,which can provide guidance and references for the practice of humanistic care in the field of hospice care,promoting the standardization and humanization of hospice care services.

Objective:To explore the associations of temperature, relative humidity, and their interaction effect with fall risk.Methods:Data on fall cases were collected using the national injury surveillance system from May to September, in 2006-2022 in Hubei Province. Combined with the meteorological and air pollution data, we conducted a time-stratified case-crossover design and used conditional logistic regression models and distributed lag nonlinear models to examine the exposure-response relationships between temperature, humidity, and fall risk. We further divided the low and the high temperature groups and the low and the high relative humidity groups and analyzed the excess risk ( ER) of falls attributed to dry-hot or wet-hot events. Finally, we calculated the additive interactions of temperature and humidity on fall risk. Results:A total of 55 401 fall cases were included. With the increase in temperature and relative humidity decrease, the exposure-response curves of fall showed nonlinear upward trends among all populations. Gender and age differences were found in temperature-fall and relative humidity-fall risk relationships. Compared with wet-non-hot (normal temperature and high relative humidity) events, the ER of fall in dry-hot (high temperature and low relative humidity) events was 14.80% (95% CI: 9.69%- 20.15%), and the ER of wet-hot (high temperature and high relative humidity) events was 9.59% (95% CI: 2.52%-17.13%). However, there was no statistically significant difference between dry-hot and wet-hot events in the fall, and no statistically significant difference between different genders, ages, occupations, and fall occurred place (all P>0.05). No significant synergistic additive interaction was found between temperature and relative humidity on fall risk (relative excess risk due to interaction=-0.08, 95% CI: -0.19-0.02). Conclusions:Higher temperatures and lower relative humidity were associated with increased fall risk. Both dry-hot and wet-hot events had a higher risk of fall, while high temperature and low humidity have no synergistic effect on fall risk.

OBJECTIVE To retrospectively analyze the drug resistance characteristics of the patients with multidrug-resistant organisms(MDROs)infections who were hospitalized from 2022 to 2023 and observe the effect of multi-disciplinary teamwork(MDT)mode so as to provide scientific bases for prevention and control of MDROs infec-tions and hospital-associated infections.METHODS A total of 639 patients with MDROs infection who were hospi-talized in Jianyang People's Hospital from Jan.2022 to Dec.2023 were recruited as the research subjects.The clinical data were collected from the patients,the drug resistance characteristics of bacteria were analyzed.The effects of MDT and pharmacological supervision on treatment of the patients with MDROs infection were observed and compared.RESULTS The methicillin-resistant Staphylococcus aureus(MRSA)(359 strains,56.18％)was dominant among the pathogens isolated from the 639 patients with MDROs infections,followed by the carbapen-em-resistant Klebsiella pneumoniae(CRKP)(96 strains,15.02％)and carbapenem-resistant Acinetobacter bau-mannii(82 strains,12.83％).Of the patients with MDROs infection,150(23.47％)were from critical care medicine department,94(14.71％)from pediatrics department,and 82(12.83％)from general surgery de-partment.The result of drug susceptibility test showed that the S.aureus strains were susceptible to linezolid,daptomycin,vancomycin and tigecycline;most of the gram-negative bacteria were susceptible to carbapenems,while the A.baumannii strains were highly resistant to the commonly used antibiotics.The total isolation rate of MDROs and the case-time infection rate of MDROs infections were 14.32％and 0.05％,respectively,after MDT and pharmacological supervision were carried out,lower than those before carried out;the effective treatment rate of the patients with MDROs was 76.47％after MDT and pharmacological supervision were carried out,higher than that before they were carried out,and there were significant differences(all P＜0.05).CONCLUSION MDT and pharmacological supervision may improve the curative effect of the patients with MDROs infection and reduce the isolation rate of MDROs as well as the incidence of hospital-associated infections.

OBJECTIVE To retrospectively analyze the drug resistance characteristics of the patients with multidrug-resistant organisms(MDROs)infections who were hospitalized from 2022 to 2023 and observe the effect of multi-disciplinary teamwork(MDT)mode so as to provide scientific bases for prevention and control of MDROs infec-tions and hospital-associated infections.METHODS A total of 639 patients with MDROs infection who were hospi-talized in Jianyang People's Hospital from Jan.2022 to Dec.2023 were recruited as the research subjects.The clinical data were collected from the patients,the drug resistance characteristics of bacteria were analyzed.The effects of MDT and pharmacological supervision on treatment of the patients with MDROs infection were observed and compared.RESULTS The methicillin-resistant Staphylococcus aureus(MRSA)(359 strains,56.18％)was dominant among the pathogens isolated from the 639 patients with MDROs infections,followed by the carbapen-em-resistant Klebsiella pneumoniae(CRKP)(96 strains,15.02％)and carbapenem-resistant Acinetobacter bau-mannii(82 strains,12.83％).Of the patients with MDROs infection,150(23.47％)were from critical care medicine department,94(14.71％)from pediatrics department,and 82(12.83％)from general surgery de-partment.The result of drug susceptibility test showed that the S.aureus strains were susceptible to linezolid,daptomycin,vancomycin and tigecycline;most of the gram-negative bacteria were susceptible to carbapenems,while the A.baumannii strains were highly resistant to the commonly used antibiotics.The total isolation rate of MDROs and the case-time infection rate of MDROs infections were 14.32％and 0.05％,respectively,after MDT and pharmacological supervision were carried out,lower than those before carried out;the effective treatment rate of the patients with MDROs was 76.47％after MDT and pharmacological supervision were carried out,higher than that before they were carried out,and there were significant differences(all P＜0.05).CONCLUSION MDT and pharmacological supervision may improve the curative effect of the patients with MDROs infection and reduce the isolation rate of MDROs as well as the incidence of hospital-associated infections.

Mussel adhesive protein (MAP) is increasingly utilized in the biomedical field for the development of various bio-inspired products such as adhesives, protective films, and coatings with diverse properties, owing to its excellent biocompatibility, low immunogenicity, broad-spectrum adhesiveness, and biodegradability. The biological effects and mechanisms of MAP include adhesive film formation, cell migration and proliferation, anti-inflammatory and antioxidant activities, and inhibition of pigment formation. In dermatological applications, MAP demonstrates a significant potential in antibacterial and antipruritic effects, wound healing, barrier repair, and scar regeneration. In recent years, advances in understanding the secretion, distribution, and adhesion mechanisms of MAP, along with innovations in extraction methods, have led to the development of various natural MAP, recombinant MAP, mussel-inspired, and mussel-mimetic biomedical products. However, the biosafety, tissue compatibility, and functionality of these products remain subjects of debate. Further investigation is needed to elucidate the interactions between MAP-based products and various organ tissues and cells within complex biological systems, as well as to thoroughly evaluate their safety and efficacy. Such efforts are essential to achieve high-value utilization of MAP and to explore broader application prospects. Future research may focus on integrating MAP with emerging technologies such as nanotechnology and smart materials to further develop its multifunctional applications in the field of dermatology.