Trends in the incidence and survival of women with hormone receptor-positive breast cancer from 1990 to 2019: a large population-based analysis.

Hormone receptor-positive breast cancer (BC) is the most prevalent subtype of BC and is generally correlated with a favorable prognosis. This study aimed to determine the incidence and survival trends among women diagnosed with hormone receptor-positive BC between 1990 and 2019. Female patients with hormone receptor-positive BC for calendar years 1990-2019 were obtained from the Surveillance, Epidemiology, and End Results (SEER) database and categorized into six diagnostic groups according to the year of diagnosis. Age-adjusted incidence rates (IRs) were calculated using joinpoint regression. We used the Kaplan-Meier method and multivariate Cox regression analyses to determine the association between diagnostic groups, and overall survival (OS) and BC-specific survival (BCSS). The final analysis included 370,729 women, among whom 37,943 (10.2%), 49,266 (13.3%), 55,652 (15.0%), 64,451 (17.4%), 77,127 (20.8%), and 86,290 (23.3%) were diagnosed between 1990 and 1994, 1995-1999, 2000-2004, 2005-2009, 2010-2014, and 2015-2019, respectively. Within the overall cohort, IRs gradually increased from 70 per 100,000 in 1990 to 113 per 100,000 in 2019 (average annual percent change, 1.59%; 95% CI, 1.18-1.99). Multivariate Cox regression analysis revealed that the survival outcomes gradually improved over nearly three decades among hormone receptor-positive BC patients, with a 0.8% and 1.3% decrease in risk for all-cause and BC-specific mortality each year, respectively. Compared to 1990-1994, hormone receptor-positive BC patients diagnosed in 2015-2019 had a 22% lower risk of all-cause death (hazard ratio [HR], 0.78; 95% CI, 0.76-0.81) and a 27% lower risk of BC-specific death (HR, 0.73; 95% CI, 0.70-0.76). The development of treatment strategies within the past three decades, especially endocrine therapy, may contribute to the continuous improvement of clinical outcomes in patients with hormone receptor-positive BC.

Current insights on mitochondria-associated endoplasmic reticulum membranes (MAMs) and their significance in the pathophysiology of ocular disorders.

The intricate interaction network necessary for essential physiological functions underscores the interdependence among eukaryotic cells. Mitochondria-Associated Endoplasmic Reticulum Membranes (MAMs), specialized junctions between mitochondria and the ER, were recently discovered. These junctions participate in various cellular processes, including calcium level regulation, lipid metabolism, mitochondrial integrity maintenance, autophagy, and inflammatory responses via modulating the structure and molecular composition of various cellular components. Therefore, MAMs contribute to the pathophysiology of numerous ocular disorders, including Diabetic Retinopathy (DR), Age-related Macular Degeneration (AMD) and glaucoma. In addition to providing a concise overview of the architectural and functional aspects of MAMs, this review explores the key pathogenetic pathways involving MAMs in the development of several ocular disorders.

Dyadic coping and related factors among couples with colorectal cancer: A latent profile analysis.

Objective: This study aimed to identify latent subgroups of dyadic coping (DC) among colorectal cancer (CRC) patients and their spousal caregivers, and to explore the factors associated with these subgroups. Methods: We conducted a cross-sectional study involving 268 pairs of CRC patients and their spousal caregivers. Participants completed the General Information Questionnaire, the Dyadic Coping Inventory, the Cancer-Related Communication Problems Scale, and the Fear of Progress Questionnaire-Short Form. Latent profile analysis (LPA) of DC among CRC couples was performed using Mplus 8.3. We compared couple illness communication, fear of cancer recurrence (FCR), and demographic characteristics between the identified subgroups and conducted ordinal logistic regression analysis to examine factors associated with these subgroups. Results: The 268 pairs of CRC patients and their spousal caregivers were classified into four subgroups based on their coping levels: low-DC group (12.3%), low common-DC group (7.1%), moderate-DC group (52.6%), and high-DC group (28.0%). Disease stage, couple illness communication, and spouse's FCR were significantly associated with the four subgroups. Conclusions: There is considerable variability in DC levels among CRC patients and their spousal caregivers. Patients with advanced disease stages, inadequate communication between spouses, and severe RCR exhibit lower levels of DC. These findings provide a theoretical basis for nursing personnel to develop personalized intervention strategies tailored to the characteristics of these subgroups.

YAP O-GlcNAcylation contributes to corneal epithelial cell ferroptosis under cigarette smoke exposure.

Cigarette smoke (CS) is an important indoor air pollutant associated with an increased risk of ocular surface disease. As the eye's outermost layer, the cornea is highly sensitive to air pollutants like CS. However, the specific mechanisms linking CS exposure to corneal dysfunction have not been fully elucidated. In the present study, we found that CS exposure damages corneal epithelial cells, accompanied by increased iron (Fe2+) levels and lipid peroxidation, both hallmarks of ferroptosis. Ferroptosis inhibitors, including Ferrostatin-1 (Fer-1) and Deferoxamine mesylate (DFO), protect against CS-induced cell damage. To understand the underlying mechanisms, we investigated how CS affects iron and lipid metabolism. Our results showed that CS could upregulate intracellular iron levels by increasing TFRC expression and promote lipid peroxidation by increasing ACSL4 expression. Silencing ACSL4 or TFRC expression prevented CS-induced ferroptosis. Furthermore, we found that the upregulation of TFRC and ACSL4 was driven by increased YAP transcription. Pharmacological or genetic inhibition of YAP effectively prevented corneal epithelial cell ferroptosis under CS stimulation. Additionally, our results suggest that CS exposure could increase O-GlcNAc transferase activity, leading to YAP O-GlcNAcylation. This glycosylation of YAP interfered with its K48-linked ubiquitination, resulting in YAP stabilization. Collectively, we found that CS exposure induces corneal epithelial cell ferroptosis via the YAP O-GlcNAcylation, and provide evidence that CS exposure is a strong risk factor for ocular surface disease.

Baculovirus-mediated endostatin and angiostatin activation of autophagy through the AMPK/AKT/mTOR pathway inhibits angiogenesis in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a highly vascularized carcinoma, and targeting its neovascularization represents an effective therapeutic approach. Our previous study demonstrated that the baculovirus-mediated endostatin and angiostatin fusion protein (BDS-hEA) effectively inhibits the angiogenesis of vascular endothelial cells and the growth of HCC tumors. However, the mechanism underlying its anti-angiogenic effect remains unclear. Increasing evidence suggests that autophagy has a significant impact on the function of vascular endothelial cells and response to cancer therapy. Hence, the objective of this research was to investigate the correlation between BDS-hEA-induced angiogenesis inhibition and autophagy, along with potential regulatory mechanisms. Our results demonstrated that BDS-hEA induced autophagy in EA.hy926 cells, as evidenced by the increasing number of autophagosomes and reactive oxygen species, accompanied by an upregulation of Beclin-1, LC3-II/LC3-I, and p62 protein expression. Suppression of autophagy using 3-methyladenine attenuated the functions of BDS-hEA-induced EA.hy926 cells, including the viability, proliferation, invasion, migration, and angiogenesis. Moreover, BDS-hEA induced autophagy by downregulating the expression of CD31, VEGF, and VEGFR2, as well as phosphorylated protein kinase B (p-AKT) and phosphorylated mammalian target of rapamycin (p-mTOR), while concurrently upregulating phosphorylated AMP-activated protein kinase (p-AMPK). The in vivo results further indicated that inhibition of autophagy by chloroquine significantly impeded the ability of BDS-hEA to suppress HCC tumor growth in mice. Mechanistically, BDS-hEA prominently facilitated autophagic apoptosis in tumor tissues and decreased the levels of ki67, CD31, VEGF, MMP-9, p-AKT, and p-mTOR while simultaneously enhancing the p-AMPK expression. In conclusion, our findings suggest that BDS-hEA induces autophagy as a cytotoxic response by modulating the AMPK/AKT/mTOR signaling pathway, thereby exerting anti-angiogenic effects against HCC.

Association between social determinants of health and survival among the US cancer survivors population.

BACKGROUND: Racial and ethnic disparities in mortality persist among US cancer survivors, with social determinants of health (SDoH) may have a significant impact on these disparities. METHODS: A population-based cohort study of a nationally representative sample of adult cancer survivors, who participated in the US National Health and Nutrition Examination Survey from 1999 to 2018 was included. Sociodemographic characteristics and SDoH were self-reported using standardized questionnaires in each survey cycle. The SDoH was examined by race and estimated for associations with primary outcomes, which included all-cause and cancer-specific mortality. Multiple mediation analysis was performed to assess the contribution of each unfavorable SDoH to racial disparities to all-cause and cancer-specific mortality. RESULTS: Among 5163 cancer survivors (2724 [57.7%] females and 3580 [69.3%] non-Hispanic White individuals), only 881 (24.9%) did not report an unfavorable SDoH. During the follow-up period of up to 249 months (median 81 months), 1964 deaths were recorded (cancer, 624; cardiovascular, 529; other causes, 811). Disparities in all-cause and cancer-specific mortality were observed between non-Hispanic Black and White cancer survivors. Unemployment, lower economic status, education less than high school, government or no private insurance, renting a home or other arrangements, and social isolation were significantly and independently associated with worse overall survival. Unemployment, lower economic status, and social isolation were significantly associated with cancer-specific mortality. Compared to patients without an unfavorable SDoH, the risk of all-cause mortality was gradually increased in those with a cumulative number of unfavorable SDoHs (1 unfavorable SDoH: hazard ratio [HR] = 1.54, 95% CI 1.25-1.89; 2 unfavorable SDoHs: HR = 1.81, 95% CI 1.46-2.24; 3 unfavorable SDoHs: HR = 2.42, 95% CI 1.97-2.97; 4 unfavorable SDoHs: HR = 3.22, 95% CI 2.48-4.19; 5 unfavorable SDoHs: HR = 3.99, 95% CI 2.99-5.33; 6 unfavorable SDoHs: HR = 6.34 95% CI 4.51-8.90). A similar trend existed for cancer-specific mortality. CONCLUSIONS: In this cohort study of a nationally representative sample of US cancer survivors, a greater number of unfavorable SDoH was associated with increased risks of mortality from all causes and cancer. Unfavorable SDoH levels were critical risk factors for all-cause and cancer-specific mortality, as well as the underlying cause of racial all-cause mortality disparities among US cancer survivors.

Beautoide A, an Anti-Osteoclastogenic Steroid from Beauveria sp. NBUF147 Associated with an Irciniidae Sponge from the Marine Mesophotic Zone.

Mesophotic coral ecosystems (MCEs), located at depths ranging from 30-150 m, host some of the most diverse yet least explored marine bioresources, particularly significant for the discovery of new bioactive molecules. The fungus Beauveria sp. NBUF147, associated with an Irciniidae sponge from the mesophotic zone at a depth of 82 m, underwent chemical investigation that led to the identification of one new sterol, beautoide A (1), and one reported sterol, 3ß,5α,9α-trihydroxy-(22E,24R)-ergosta-7,22-dien-6-one (2). Their structures were determined from analysis of spectroscopic data and X-ray crystallography. Evaluation of biological activity in prednisolone-induced osteoporotic zebrafish showed that 1 was anti-osteoclastogenic in vivo at 3.0 µM.

Peroxiredoxin 6 Protects Pulmonary Epithelial Cells From Cigarette-related Ferroptosis in Chronic Obstructive Pulmonary Disease.

Peroxiredoxin 6 (PRDX6) has a protective effect on pulmonary epithelial cells against cigarette smoke (CS)-induced ferroptosis. This study investigates the role of PRDX6 in the development of chronic obstructive pulmonary disease (COPD) and its possibility as a target. We observed that PRDX6 was downregulated in lung tissues of COPD patients and in CS-stimulated cells. The degradation of PRDX6 could be through the lysosomal pathway. PRDX6 deficiency exacerbated pulmonary inflammation and mucus hypersecretion in vivo. Overexpression of PRDX6 in Beas-2B cells ameliorated CS-induced cell death and inflammation, suggesting its protective role against CS-induced damage. Furthermore, PRDX6 deficiency promoted ferroptosis by adding the content of iron and reactive oxygen species, while iron chelation with deferoxamine mitigated CS-induced ferroptosis, cell death, and inflammatory infiltration both in vitro and in vivo. The critical role of PRDX6 in regulating ferroptosis suggests that targeting PRDX6 or iron metabolism may represent a promising strategy for COPD treatment.

Advanced treatment and reuse of dye wastewater using thermo-irreversible on/off switch starch with disruption of dissolution/precipitation dynamic equilibrium.

The development of irreversible on/off switching materials is a potential strategy for unidirectional capture and encapsulation of pollutants, preventing the pollutant leakage problem resulting from the reversible dissolution of flocculants. Herein, a thermo-irreversible on/off switch starch (TISS) is prepared through modifying starch by etherification grafting glycidyl phenyl ether and 2,4-bis(dimethylamino)-6-chloro-[1,3,5]-triazine. It breaks the dissolution/precipitation dynamic equilibrium across heating-cooling cycles by thermal-induced irreversible coil-to-globule self-assembly of polymer chains, resulting in a 50-fold decrease in polymer solubility. Particularly, TISS shows a superior double-locking effect on pollutants and flocculants through its unique irreversible conformation memory capability, leading to a high-quality reuse water. 99.9 % of reactive brilliant red dye and 97.9 % of TISS remain fixed within sludge flocs even after prolonged immersion in cold water at 24 °C for 60 days. Furthermore, direct recycling and reuse of dye-bath energy can be realized through the isothermal flocculation and dyeing method, showing a 75 % decrease in energy consumption after three cycles compared to traditional dyeing techniques. This work presents a novel approach to constructing an irreversible pollutant delivery system using thermo-irreversible on/off switch starch, addressing the problems of high energy dissipation and water quality fluctuations during wastewater treatment.

Antitumor activity and transcriptome sequencing (RNA-seq) analyses of hepatocellular carcinoma cells in response to exposure triterpene-nucleoside conjugates.

Fifteen betulonic/betulinic acid conjugated with nucleoside derivatives were synthesized to enhance antitumor potency and water solubility. Among these, the methylated betulonic acid-azidothymidine compound (8c) exhibited a broad-spectrum of antitumor activity against three tested tumor cell lines, including SMMC-7721 (IC50 = 5.02 µM), KYSE-150 (IC50 = 5.68 µM), and SW620 (IC50 = 4.61 µM) and along with lower toxicity (TC50 > 100 µM) estimated by zebrafish embryos assay. Compared to betulinic acid (<0.05 µg/mL), compound 8c showed approximately 40-fold higher water solubility (1.98 µg/mL). In SMMC-7721 cells, compound 8c induced autophagy and apoptosis as its concentration increased. Transcriptomic sequencing analysis was used to understand the potential impacts of the underlying mechanism of 8c on SMMC-7721 cells. Transcriptomic studies indicated that compound 8c could activate autophagy by inhibiting the PI3K/AKT pathway in SMMC-7721 cells. Furthermore, in the xenograft mice study, compound 8c significantly slowed down the tumor growth, as potent as paclitaxel treated group. In conclusion, methylated betulonic acid-azidothymidine compound (8c) not only increases water solubility, but also enhances the potency against hepatocellular carcinoma cells by inducing autophagy and apoptosis, and suppressing the PI3K/Akt/mTOR signaling pathway.

Polystyrene nanoplastics induce lipophagy via the AMPK/ULK1 pathway and block lipophagic flux leading to lipid accumulation in hepatocytes.

Micro- and nanoplastic pollution has emerged as a significant global concern due to their extensive presence in the environment and potential adverse effects on human health. Nanoplastics can enter the human circulatory system and accumulate in the liver, disrupting hepatic metabolism and causing hepatotoxicity. However, the precise mechanism remains uncertain. Lipophagy is an alternative mechanism of lipid metabolism involving autophagy. This study aims to explore how polystyrene nanoplastics (PSNPs) influence lipid metabolism in hepatocytes via lipophagy. Initially, it was found that PSNPs were internalized by human hepatocytes, resulting in decreased cell viability. PSNPs were found to induce the accumulation of lipid droplets (LDs), with autophagy inhibition exacerbating this accumulation. Then, PSNPs were proved to activate lipophagy by recruiting LDs into autophagosomes and block the lipophagic flux by impairing lysosomal function, inhibiting LD degradation. Ultimately, PSNPs were shown to activate lipophagy through the AMPK/ULK1 pathway, and knocking down AMPK exacerbated lipid accumulation in hepatocytes. Overall, these results indicated that PSNPs triggered lipophagy via the AMPK/ULK1 pathway and blocked lipophagic flux, leading to lipid accumulation in hepatocytes. Thus, this study identifies a novel mechanism underlying nanoplastic-induced lipid accumulation, providing a foundation for the toxicity study and risk assessments of nanoplastics.

Association between indoor residual spraying and the malaria burden in Zambia and factors associated with IRS refusals: a case-control study in Vubwi District.

BACKGROUND: Indoor residual spraying (IRS) has been implemented to prevent malaria in Zambia for several decades, but its effectiveness has not been evaluated long term and in Vubwi District yet. This study aimed to assess the association between IRS and the malaria burden in Zambia and Vubwi District and to explore the factors associated with refusing IRS. METHODS: A retrospective study was used to analyze the association between IRS and malaria incidence in Zambia in 2001-2020 and in Vubwi District in 2014-2020 by Spearman correlation analysis. A case-control study was used to explore the factors associated with IRS refusals by households in Vubwi District in 2021. A logistic regression model was performed to identify factors associated with IRS refusals. RESULTS: The malaria incidence reached its peak (391/1000) in 2001 and dropped to the lowest (154/1000) in 2019. The annual percentage change in 2001-2003, 2003-2008, 2008-2014, 2014-2018 and 2018-2020 was - 6.54%, - 13.24%, 5.04%, - 10.28% and 18.61%, respectively. A significantly negative correlation between the percentage of population protected by the IRS against the total population in Zambia (coverage) and the average malaria incidence in the whole population was observed in 2005-2020 (r = - 0.685, P = 0.003) and 2005-2019 (r = - 0.818, P < 0.001). Among 264 participants (59 in the refuser group and 205 in the acceptor group), participants with specific occupations (self-employed: OR 0.089, 95% CI 0.022-0.364; gold panning: OR 0.113, 95% CI 0.022-0.574; housewives: OR 0.129, 95% CI 0.026-0.628 and farmers: OR 0.135, 95% CI 0.030-0.608 compared to employees) and no malaria case among household members (OR 0.167; 95% CI 0.071-0.394) had a lower risk of refusing IRS implementation, while those with a secondary education level (OR 3.690, 95% CI 1.245-10.989) had a higher risk of refusing IRS implementation compared to those who had never been to school. CONCLUSIONS: Increasing coverage with IRS was associated with decreasing incidence of malaria in Zambia, though this was not observed in Vubwi District, possibly because of the special geographical location of Vubwi District. Interpersonal communication and targeted health education should be implemented at full scale to ensure household awareness and gain community trust.

Factors Influencing the Self-management of Breast Cancer-Related Lymphedema: A Meta-synthesis of Qualitative Studies.

BACKGROUND: Patients with breast cancer have an estimated 14% to 60% risk of developing lymphedema after treatment. Self-management behavior strategies regarding lymphedema are essential in preventing and alleviating the severity of lymphedema. OBJECTIVE: The aim of this study was to evaluate qualitative research evidence on the potential influencing factors for self-management behaviors of lymphedema in patients with breast cancer. METHODS: A systematic search of 10 electronic databases was conducted to identify qualitative studies on patient experience of lymphedema self-management. The following databases were included and appraised using the Joanna Briggs Institute Critical Appraisal Checklist: Cochrane Library, PubMed, EMBASE, Web of Science, PsycINFO, Scopus, Cumulative Index to Nursing and Allied Health Literature, China National Knowledge Infrastructure, Wanfang Med Online, and Chinese Biomedical Database. RESULTS: The literature search yielded 5313 studies, of which only 22 qualitative studies fulfilled the eligibility criteria. Five synthesized findings were derived encompassing personal characteristics, personal knowledge and experience, personal health beliefs, self-regulation skills and abilities, and social influences and support. CONCLUSIONS: Patients with breast cancer are confronted with many challenges when performing self-management of lymphedema. Therefore, it is important to recognize potential facilitators and barriers to further offer practical recommendations that promote self-management activities for lymphedema. IMPLICATIONS FOR PRACTICE: Healthcare professionals should receive consistent training on lymphedema management. On the basis of individual patient characteristics, tailored education and support should be provided, including transforming irrational beliefs, and improving related knowledge and skills, with the aim to promote self-management behaviors with respect to lymphedema.

Iron Overload-Dependent Ferroptosis Aggravates LPS-Induced Acute Lung Injury by Impairing Mitochondrial Function.

Ferroptosis is a newly proposed form of programmed cell death that is iron-dependent and closely linked to oxidative stress. Its specific morphological changes include shrunken mitochondria, increased density of mitochondrial membrane, and rupture or disappearance of mitochondrial cristae. The main mechanism of ferroptosis involves excessive free iron reacting with membrane phospholipids, known as the Fenton reaction, resulting in lipid peroxidation. However, the role of iron in acute lung injury (ALI) remains largely unknown. In this study, LPS was instilled into the airway to induce ALI in mice. We observed a significant increase in iron concentration during ALI, accompanied by elevated levels of lipid peroxidation markers such as malonaldehyde (MDA) and 4-hydroxynonenal (4-HNE). Treatment with the iron chelator deferoxamine (DFO) or ferroptosis inhibitor ferrostatin-1 (Fer-1) reversed lipid peroxidation and significantly attenuates lung injury. Similarly, DFO or Fer-1 treatment improved the cell survival significantly in vitro. These results demonstrated that ferroptosis occurs during ALI and that targeting ferroptosis is an effective treatment strategy. Interestingly, we found that the increased iron was primarily concentrated in mitochondria and DFO treatment effectively restored normal mitochondria morphology. To further confirm the damaging effect of iron on mitochondria, we performed mitochondrial stress tests in vitro, which revealed that iron stimulation led to mitochondrial dysfunction, characterized by impaired basal respiratory capacity, ATP production capacity, and maximum respiratory capacity. MitoTEMPO, an antioxidant targeting mitochondria, exhibited superior efficacy in improving iron-induced mitochondrial dysfunction compared to the broad-spectrum antioxidant NAC. Treatment with MitoTEMPO more effectively alleviated ALI. In conclusion, ferroptosis contributes to the pathogenesis of ALI and aggravates ALI by impairing mitochondrial function.

ROS-mediated NRF2/p-ERK1/2 signaling-involved mitophagy contributes to macrophages activation induced by CdTe quantum dots.

Cadmium telluride (CdTe) quantum dots (QDs) have garnered significant attention for tumor imaging due to their exceptional properties. However, there remains a need for further investigation into their potential toxicity mechanisms and corresponding enhancements. Herein, CdTe QDs were observed to accumulate in mouse liver, leading to a remarkable overproduction of IL-1ß and IL-6. Additionally, there was evidence of macrophage infiltration and activation following exposure to 12.5 µmol/kg body weight of QDs. To elucidate the underlying mechanism of macrophage activation, CdTe QDs functionalized with 3-mercaptopropionic acid (MPA) were utilized. In vitro experiments revealed that 1.0 µM MPA-CdTe QDs activated PINK1-dependent mitophagy in RAW264.7 macrophages. Critically, the autophagic flux remained unimpeded, as demonstrated by the absence of p62 accumulation, LC3 turnover assay results, and successful fusion of autophagosomes with lysosomes. Mechanically, QDs increased reactive oxygen species (ROS) and mitoROS by damaging both mitochondria and lysosomes. ROS, in turn, inhibited NRF2, resulting in the phosphorylation of ERK1/2 and subsequent activation of mitophagy. Notably, 1.0 µM QDs disrupted lysosomes but autophagic flux was not impaired. Eventually, the involvement of the ROS-NRF2-ERK1/2 pathway-mediated mitophagy in the increase of IL-1ß and IL-6 in macrophages was confirmed using Trolox, MitoTEMPO, ML385, specific siRNAs, and lentivirus-based interventions. This study innovatively revealed the pro-inflammatory rather than anti-inflammatory role of mitophagy in nanotoxicology, shedding new light on the mechanisms of mitochondrial disorders induced by QDs and identifying several molecular targets to comprehend the toxicological mechanisms of CdTe QDs.

Janus liposozyme for the modulation of redox and immune homeostasis in infected diabetic wounds.

Diabetic foot ulcers often become infected, leading to treatment complications and increased risk of loss of limb. Therapeutics to manage infection and simultaneously promote healing are needed. Here we report on the development of a Janus liposozyme that treats infections and promotes wound closure and re-epithelialization. The Janus liposozyme consists of liposome-like selenoenzymes for reactive oxygen species (ROS) scavenging to restore tissue redox and immune homeostasis. The liposozymes are used to encapsulate photosensitizers for photodynamic therapy of infections. We demonstrate application in methicillin-resistant Staphylococcus aureus-infected diabetic wounds showing high ROS levels for antibacterial function from the photosensitizer and nanozyme ROS scavenging from the liposozyme to restore redox and immune homeostasis. We demonstrate that the liposozyme can directly regulate macrophage polarization and induce a pro-regenerative response. By employing single-cell RNA sequencing, T cell-deficient Rag1-/- mice and skin-infiltrated immune cell analysis, we further reveal that IL-17-producing γδ T cells are critical for mediating M1/M2 macrophage transition. Manipulating the local immune homeostasis using the liposozyme is shown to be effective for skin wound repair and tissue regeneration in mice and mini pigs.

Lipidome is a valuable tool for the severity prediction of coronavirus disease 2019.

Objective: To describe the lipid metabolic profile of different patients with coronavirus disease 2019 (COVID-19) and contribute new evidence on the progression and severity prediction of COVID-19. Methods: This case-control study was conducted in Peking University Third Hospital, China. The laboratory-confirmed COVID-19 patients aged ≥18 years old and diagnosed as pneumonia from December 2022 to January 2023 were included. Serum lipids were detected. The discrimination ability was calculated with the area under the curve (AUC). A random forest (RF) model was conducted to determine the significance of different lipids. Results: Totally, 44 COVID-19 patients were enrolled with 16 mild and 28 severe patients. The top 5 super classes were triacylglycerols (TAG, 55.9%), phosphatidylethanolamines (PE, 10.9%), phosphatidylcholines (PC, 6.8%), diacylglycerols (DAG, 5.9%) and free fatty acids (FFA, 3.6%) among the 778 detected lipids from the serum of COVID-19 patients. Certain lipids, especially lysophosphatidylcholines (LPCs), turned to have significant correlations with certain immune/cytokine indexes. Reduced level of LPC 20:0 was observed in severe patients particularly in acute stage. The AUC of LPC 20:0 reached 0.940 in discriminating mild and severe patients and 0.807 in discriminating acute and recovery stages in the severe patients. The results of RF models also suggested the significance of LPCs in predicting the severity and progression of COVID-19. Conclusion: Lipids probably have the potential to differentiate and forecast the severity, progression, and clinical outcomes of COVID-19 patients, with implications for immune/inflammatory responses. LPC 20:0 might be a potential target in predicting the progression and outcome and the treatment of COVID-19.

Gonadal transcriptome analysis of genes related to sex differentiation and sex development in the Pomacea canaliculata.

As an invasive alien animal, Pomacea canaliculata poses a great danger to the ecology and human beings. Recently, there has been a gradual shift towards bio-friendly control. Based on the development of RNA interference and CRISPR technology as molecular regulatory techniques for pest control, it was determined if the knockout of genes related to sex differentiation in P. canaliculata could induce sterility, thereby helping in population control. However, the knowledge of sex differentiation- and development-related genes in P. canaliculata is currently lacking. Here, transcriptomic approaches were used to study the genes expressed in the two genders of P. canaliculata at various developmental stages. Gonad transcriptomes of immature or mature males and females were compared, revealing 12,063 genes with sex-specific expression, of which 6066 were male- and 5997 were female-specific. Among the latter, 581 and 235 genes were up-regulated in immature and mature females, respectively. The sex-specific expressed genes identified included GnRHR2 and TSSK3 in males and ZAR1 and WNT4 in females. Of the genes, six were involved in reproduction: CCNBLIP1, MND1, DMC1, DLC1, MRE11, and E(sev)2B. Compared to immature snail gonads, the expression of HSP90 and CDK1 was markedly reduced in gonadal. It was hypothesized that the two were associated with the development of females. These findings provided new insights into crucial genetic information on sex differentiation and development in P. canaliculata. Additionally, some candidate genes were explored, which can contribute to future studies on controlling P. canaliculata using molecular regulatory techniques.

Developing Isomeric Peptides for Mimicking the Sequence-Activity Landscapes of Enzyme Evolution.

Enzymes catalyze almost all material conversion processes within living organisms, yet their natural evolution remains unobserved. Short peptides, derived from proteins and featuring active sites, have emerged as promising building blocks for constructing bioactive supramolecular materials that mimic native proteins through self-assembly. Herein, we employ histidine-containing isomeric tetrapeptides KHFF, HKFF, KFHF, HFKF, FKHF, and FHKF to craft supramolecular self-assemblies, aiming to explore the sequence-activity landscapes of enzyme evolution. Our investigations reveal the profound impact of peptide sequence variations on both assembly behavior and catalytic activity as hydrolytic simulation enzymes. During self-assembly, a delicate balance of multiple intermolecular interactions, particularly hydrogen bonding and aromatic-aromatic interactions, influences nanostructure formation, yielding various morphologies (e.g., nanofibers, nanospheres, and nanodiscs). Furthermore, the analysis of the structure-activity relationship demonstrates a strong correlation between the distribution of the His active site on the nanostructures and the formation of the catalytic microenvironment. This investigation of the sequence-structure-activity paradigm reflects how natural enzymes enhance catalytic activity by adjusting the primary structure during evolution, promoting fundamental research related to enzyme evolutionary processes.

An efficient electrochemical sensor based on the Ce-MOF/g-C3N5 composite for the detection of nitrofurazone.

The Ce-MOF/g-C3N5 composite was first constructed using a simple reflux method in an oil bath. Herein, we report that the electrochemical sensor fabricated based on this composite exhibits high performance in the detection of nitrofurazone. Interestingly, this sensor exhibits an extra-wide linear range of detection composed of two line segments (7-100 µM and 100-2913 µM), as well as a low detection limit (LOD) of 6.15 µM (S/N = 3) under optimal experimental conditions. Additionally, the sensor demonstrates exceptional selectivity, reproducibility and stability. More importantly, the proposed electrochemical sensor can effectively monitor nitrofurazone in real samples such as urea and tap water, and obtain ideal recoveries. The sensor has such excellent performance because of the synergistic effect of the two components in the Ce-MOF/g-C3N5 composite. Compared with Ce-MOF, the introduction of g-C3N5 effectively not only enhances the conductivity of Ce-MOF/g-C3N5 but also exposes more active sites, which is conducive to increasing the electrocatalytic activity to reduce nitrofurazone. This research contributes new scientific research ideas for fabricating ideal electrochemical sensors based on g-C3N5 and MOFs.