Allergies to Allergens from Cats and Dogs: A Review and Update on Sources, Pathogenesis, and Strategies.

Inhalation allergies caused by cats and dogs can lead to a range of discomforting symptoms, such as rhinitis and asthma, in humans. With the increasing popularity of and care provided to these companion animals, the allergens they produce pose a growing threat to susceptible patients' health. Allergens from cats and dogs have emerged as significant risk factors for triggering asthma and allergic rhinitis worldwide; however, there remains a lack of systematic measures aimed at assisting individuals in recognizing and preventing allergies caused by these animals. This review provides comprehensive insights into the classification of cat and dog allergens, along with their pathogenic mechanisms. This study also discusses implementation strategies for prevention and control measures, including physical methods, gene-editing technology, and immunological approaches, as well as potential strategies for enhancing allergen immunotherapy combined with immunoinformatics. Finally, it presents future prospects for the prevention and treatment of human allergies caused by cats and dogs. This review will improve knowledge regarding allergies to cats and dogs while providing insights into potential targets for the development of next-generation treatments.

School-based factors influencing physical activity participation in children and adolescents with disabilities: A qualitative systematic review and meta-synthesis.

BACKGROUND: Children and adolescents with disabilities (CAD) frequently encounter barriers to participation in physical activity (PA). Schools play a vital role in promoting PA, making it crucial to understand the school-based factors influencing CAD's PA participation. OBJECTIVE: This qualitative systematic review and meta-synthesis aims to identify and elucidate the school-based factors influencing PA engagement among this population. METHODS: A comprehensive search across six databases-Web of Science, PsycINFO, Scopus, SPORTDiscus, and Embase, CNKI-was conducted in August 2023, and subsequently updated in April 2024. English or Chinese peer-reviewed journal articles that contained substantial qualitative data regarding school-based factors affecting PA in CAD were included. The methodological quality of included studies was evaluated utilizing the Critical Appraisal Skills Program Qualitative Checklist. Qualitative data were analyzed through thematic synthesis. RESULTS: A total of 16 studies (12 qualitative studies and 4 mixed-methods studies) were included, all of which were of moderate to high quality. Thematic synthesis identified four major themes: (a) physical environment (provision of facilities, specialized and adapted equipment, space for activities); (b) social environment (peers, school leaders, teachers and other school staff); (c) opportunities for PA (physical education, classroom movement integration, extra-curricular activities); and (d) characteristics of PA (adaption of rules and task difficulty, competition components, diversified activities, fun). CONCLUSIONS: This review reveals the complex interplay of different school-based factors affecting PA participation among CAD. The findings provide valuable insights for educators, policymakers, and health professionals to enhance PA participation in this population.

Ultra-small platinum nano-enzymatic spray with ROS scavenging and anti-inflammatory properties for photoaging treatment.

Photoaging induced by ultraviolet (UV) results in oxidative stress and inflammation. Noble metal nanozymes have strong antioxidant and anti-inflammatory capacity, which are expected to eliminate the excessive reactive oxygen species (ROS) and inflammatory factors in the photoaged skin. Hence, we have synthesized ultrasmall platinum nanoparticles coated with polyvinylpyrrolidone (Pt NPs) with a diameter of nearly 5 nm for photoaging treatment. Thanks to multi-enzymatic capacities (catalase, peroxidase, and superoxide dismutase) of Pt NPs, they can effectively protect fibroblasts from UV-induced ROS attack, relieve fibroblasts from UV-induced cell cycle arrest, downregulate matrix metalloproteinases (MMPs) to regenerate type I collagen, and inhibit M1 macrophage polarization to decrease the expression of inflammatory factors. For photoaged mice treatment, we employ the concept of routine spray skincare and encapsulate Pt NPs solution in a spray bottle. In combination with roller needle, following Pt NPs nano-enzymatic spray given, UV-induced photoaged mice display reduced wrinkle formation in the collagen-depleted dermal tissue of mice and more youthful performance in both appearance and organizational structure. Consequently, multi-enzymatic functions of Pt NPs nano-spray offers a promising avenue for anti-photoaging therapy, providing potential benefits in both preventative and restorative skincare applications.

Resistance of Aedes albopictus (Diptera: Culicidae) larvae and adults to insecticides based on bioassays and knockdown resistance (kdr) mutations in Zhejiang Province, China.

Aedes albopictus, a common mosquito in Zhejiang Province, is a carrier of more than twenty arboviruses. There are dozens or even hundreds of imported cases of dengue fever every year in Zhejiang Province, and there have also been many local outbreaks caused by imported cases of dengue fever. The objectives were to assess the resistance of larvae and adults of several Ae. albopictus strains in Zhejiang Province to commonly used pyrethroid insecticides (beta-cypermethrin, deltamethrin and permethrin), and detect mutations in the sodium channel gene, to further analyse the relationship between phenotypic resistance and the frequency of mutations. The resistance of eight field strains of Ae. albopictus larvae to beta-cypermethrin, deltamethrin and permethrin ranged from 8.17 to 36.06, 12.12-107.3 and 1.55-81.9, respectively, and there was a significant positive correlation of interaction resistance among the three insecticides. The mutation frequencies of I1532T and F1534S in the larvae of Ae. albopictus were 0-6.25 % and 42.19-100.00 %. Moreover, the diagnostic doses of the three pyrethroids for adult Ae. albopictus mosquitoes were 0.2510 g/L, 0.1562 g/L, and 0.9072 g/L. Except for the Zhoushan strain, which was suspected to be resistant to beta-cypermethrin, the other field strains were resistant to the three pyrethroids, and there was a significant positive correlation of cross-resistance among the three insecticides. The mutation frequencies of I1532T and F1534S of adult Ae. albopictus were 0-1.56 % and 62.50-100.00 %. In addition, the LC50 of the larvae and the mortality rate of adult Ae. albopictus after treatment with the three pyrethroids were significantly and positively correlated with the frequency of the F1534S mutation. F1534S mutation occurred earlier than I1532T mutation in both larvae and adult Ae. albopictus. F1534S mutation in the sodium channel gene may be a particular biomolecular detection marker for resistance to pyrethroid insecticides in Ae. albopictus in Zhejiang Province.

24-H movement behaviours research in Chinese population: A scoping review.

Background: Numerous studies examining 24-h movement behaviours have been exponentially published globally. However, no comprehensive reviews summarized and synthesized the evidence on the Chinese population. This review aimed to map the most recent research state and fill the gaps related to 24-h movement behaviours in the Chinese population. Methods: Five electronic databases (Web of Science, PubMed, Scopus, EBSCOhost, and CNKI (Chinese database)) were searched from their inceptions through October 2023. Quantitative studies published in English and/or Chinese were included if they were related to 24-h movement behaviours in the Chinese population. Results: From 9431 documents screened, 53 met the inclusion criteria. All the included studies were published between 2019 and 2023, showing a notable increasing trend over the years. Most studies used cross-sectional designs (96.2 %) and self-reported measures (56.6 %). Nearly all the studies targeted general healthy population (96.2 %), especially children and adolescents (64.2 %). The main three research topics observed were health outcomes (81.1 %), prevalence (66.0 %), and correlates (15.1 %) of 24-h movement behaviours. Conclusion: 24-h movement behaviours in the Chinese population has been an increasingly important research topic in the literature, with predominant focus on children and adolescents (study population), self-report measure (measurement), cross-sectional design (study design), guidelines adherence (study topic), and health outcomes examination (study topic). These findings delineate a research landscape in the Chinese population, and highlight the research gaps needed to be addressed. Future studies are suggested to target these research gaps, expanding evidence base for the Chinese populations. For instance, more studies using device-based measures, longitudinal or interventional designs, as well as qualitative and mixed-methods approaches are required.

The hypoglycemic effect of enzymatic modified dietary fiber from bamboo shoot on type 2 diabetes rats.

Bamboo shoot is a healthy food rich in dietary fiber (DF). However, its highly insoluble DF and fibrous texture limit its application in industrially processed foods. To achieve industrial processing of bamboo shoot, cellulase was used to improve the physical characteristics of bamboo shoot DF in this study. After enzymatic hydrolysis, the content of soluble DF (SDF) of bamboo shoot increased by 99.28% (from 5.53% to 11.02%) significantly (p < 0.01). At the same time, the effect of enzymatic-modified bamboo SDF (EMBSDF) on streptozotocin-induced type 2 diabetes rats was explored. Results demonstrated that the high dose of EMBSDF (312.8 mg/kg) treated rats showed significant improvements in terms of glucose tolerance and insulin sensitivity (p < 0.01) compared with the diabetes rats. Meantime, it was observed that the levels of glucagon-like peptide-1, adiponectin and interleukin-4 of high dose of EMBSDF compared with diabetes rats were increased (p < 0.01) by 57.79%, 159.13%, and 6.17%, respectively. The tumor necrosis factor-α, C-reactive protein, and leptin levels were decreased (p < 0.01) by 62.89%, 31.53%, and 7.84%, respectively. Furthermore, apparent kidney and pancreas histology improvements were found in high-dose and mid-dose EMBSDF-treated diabetes rats. These results indicated that the modified DF significantly improved diabetes.

Setup errors analysis in iterative kV CBCT: A clinical study of cervical cancer treated with Volumetric Modulated Arc Therapy.

OBJECTIVE: This study aims to analyze setup errors in pelvic Volumetric Modulated Arc Therapy (VMAT) for patients with non-surgical primary cervical cancer, utilizing the onboard iterative kV cone beam CT (iCBCT) imaging system on the Varian Halcyon 2.0 ring gantry structure accelerator to enhance radiotherapy precision. METHOD: We selected 132 cervical cancer patients who underwent VMAT with daily iCBCT imaging guidance. Before each treatment session, a registration method based on the bony structure was employed to acquire iCBCT images with the corresponding planning CT images. Following verification and adjustment of image registration results along the three axes (but not rotational), setup errors in the lateral (X-axis), longitudinal (Y-axis), and vertical (Z-axis) directions were recorded for each patient. Subsequently, we analyzed 3642 iCBCT image setup errors. RESULTS: The mean setup errors for the X, Y, and Z axes were 4.50 ± 3.79 mm, 6.08 ± 6.30 mm, and 1.48 ± 2.23 mm, respectively. Before correction with iCBCT, setup margins based on the Van Herk formula for the X, Y, and Z axes were 6.28, 12.52, and 3.26 mm, respectively. In individuals aged 60 years and older, setup errors in the X and Y axes were significantly larger than those in the younger group (p < 0.05). Additionally, there is no significant linear correlation between setup errors and treatment fraction numbers. CONCLUSION: Data analysis underscores the importance of precise Y-axis setup for cervical cancer patients undergoing VMAT. Radiotherapy centers without daily iCBCT should appropriately extend the planning target volume (PTV) along the Y-axis for cervical cancer patients receiving pelvic VMAT. Elderly patients exhibit significantly larger setup errors compared to younger counterparts. In conclusion, iCBCT-guided radiotherapy is recommended for cervical cancer patients undergoing VMAT to improve setup precision.

Meat consumption and incident type 2 diabetes: an individual-participant federated meta-analysis of 1·97 million adults with 100 000 incident cases from 31 cohorts in 20 countries.

BACKGROUND: Meat consumption could increase the risk of type 2 diabetes. However, evidence is largely based on studies of European and North American populations, with heterogeneous analysis strategies and a greater focus on red meat than on poultry. We aimed to investigate the associations of unprocessed red meat, processed meat, and poultry consumption with type 2 diabetes using data from worldwide cohorts and harmonised analytical approaches. METHODS: This individual-participant federated meta-analysis involved data from 31 cohorts participating in the InterConnect project. Cohorts were from the region of the Americas (n=12) and the Eastern Mediterranean (n=2), European (n=9), South-East Asia (n=1), and Western Pacific (n=7) regions. Access to individual-participant data was provided by each cohort; participants were eligible for inclusion if they were aged 18 years or older and had available data on dietary consumption and incident type 2 diabetes and were excluded if they had a diagnosis of any type of diabetes at baseline or missing data. Cohort-specific hazard ratios (HRs) and 95% CIs were estimated for each meat type, adjusted for potential confounders (including BMI), and pooled using a random-effects meta-analysis, with meta-regression to investigate potential sources of heterogeneity. FINDINGS: Among 1 966 444 adults eligible for participation, 107 271 incident cases of type 2 diabetes were identified during a median follow-up of 10 (IQR 7-15) years. Median meat consumption across cohorts was 0-110 g/day for unprocessed red meat, 0-49 g/day for processed meat, and 0-72 g/day for poultry. Greater consumption of each of the three types of meat was associated with increased incidence of type 2 diabetes, with HRs of 1·10 (95% CI 1·06-1·15) per 100 g/day of unprocessed red meat (I2=61%), 1·15 (1·11-1·20) per 50 g/day of processed meat (I2=59%), and 1·08 (1·02-1·14) per 100 g/day of poultry (I2=68%). Positive associations between meat consumption and type 2 diabetes were observed in North America and in the European and Western Pacific regions; the CIs were wide in other regions. We found no evidence that the heterogeneity was explained by age, sex, or BMI. The findings for poultry consumption were weaker under alternative modelling assumptions. Replacing processed meat with unprocessed red meat or poultry was associated with a lower incidence of type 2 diabetes. INTERPRETATION: The consumption of meat, particularly processed meat and unprocessed red meat, is a risk factor for developing type 2 diabetes across populations. These findings highlight the importance of reducing meat consumption for public health and should inform dietary guidelines. FUNDING: The EU, the Medical Research Council, and the National Institute of Health Research Cambridge Biomedical Research Centre.

Modifiable lifestyle factors and the risk of post-COVID-19 multisystem sequelae, hospitalization, and death.

Effective prevention strategies for post-COVID complications are crucial for patients, clinicians, and policy makers to mitigate their cumulative burden. This study evaluated the association of modifiable lifestyle factors (smoking, alcohol intake, BMI, physical activity, sedentary time, sleep duration, and dietary habits) with COVID-19 multisystem sequelae, death, and hospitalization in the UK Biobank cohort (n = 68,896). A favorable lifestyle (6-10 healthy factors; 46.4%) was associated with a 36% lower risk of multisystem sequelae (HR, 0.64; 95% CI, 0.58-0.69; ARR at 210 days, 7.08%; 95% CI, 5.98-8.09) compared to an unfavorable lifestyle (0-4 factors; 12.3%). Risk reductions spanned all 10 organ systems, including cardiovascular, coagulation, metabolic, gastrointestinal, kidney, mental health, musculoskeletal, respiratory disorders, and fatigue. This beneficial effect was largely attributable to direct lifestyle impacts independent of corresponding pre-infection comorbidities (71% for any sequelae). A favorable lifestyle was also related to the risk of post-COVID death (HR 0.59, 0.52-0.66) and hospitalization (HR 0.78, 0.73-0.84). These associations persisted across acute and post-acute infection phases, irrespective of hospitalization status, vaccination, or SARS-CoV-2 variant. These findings underscore the clinical and public health importance of adhering to a healthy lifestyle in mitigating long-term COVID-19 adverse impacts and enhancing future pandemic preparedness.

Photothermal therapy improves the efficacy of topical immunotherapy against melanoma.

BACKGROUND: Melanoma is an aggressive cancer with poor response to traditional therapies. A combination of photothermal therapy and topical immunotherapy may enhance elimination of melanoma.. MATERIALS AND METHODS: C57BL/6 mice with early stage and metastatic melanoma were treated with laser immunotherapy (LIT), combining near-infrared laser-based photothermal therapy (PTT) and topical imiquimod (IMQ)-based immunotherapy. The volume of primary and abscopal melanoma, animal survival, tissue temperature, transcriptome, and immune cell response were investigated to evaluate the effect of LIT. RESULTS: LIT could eliminate primary tumors, inhibite abscopal tumors, and prolong animal survival. The tumor tissues were selectively destroyed under a photothermal gradient between 38.2 ± 3.7 °C and 73.0 ± 2.3 °C. Gene expression analysis showed a significant increase in the expression of damage associated molecular patterns. Additionally, the population of mature dendritic cells, CD4+ T cells, and CD8+ T cells were increased, while myeloid-derived suppressor cells were downregulated after LIT. CONCLUSION: The study showed that LIT inhibited the growth of both primary and abscopal melanoma by activating systemic antitumor immune responses and reversing the immunosuppressive tumor microenvironment, making LIT a potential method for advanced melanoma treatment.

Selective Oxidation of Alcohol to Valuable Aldehydes Using Water as a Promoter in a Photoelectrochemical Cell.

Artificial photoelectrochemistry (PEC) has emerged as a promising and efficient technology for the sustainable conversion of solar energy into chemicals. In this study, we present a refined PEC process that enables the highly selective and stable production of piperonal and other valuable aldehydes through the oxidation of the corresponding alcohols. By employing Fe2O3 or TiO2 as the photoanode material and 2,2,6,6-tetramethylpiperidinooxy (TEMPO) as a redox mediator in an H2O/acetonitrile solution, we achieve 100% selectivity and a >95% Faradaic efficiency for piperonal production from piperonyl alcohol (PA) oxidation. Remarkably, we reveal the enhancing effect on the PA oxidation reactivity of appropriate-amount water in the solvent as it plays a crucial role in inhibiting the photoelectron-hole recombination efficiency and facilitating charge transfer. Mechanistic analysis suggests that TEMPO-mediated PA oxidation involves the formation of •O2- radicals by the reduction of oxygen on the cathode, resulting in water as the sole byproduct. Furthermore, our PEC oxidation system exhibits applications on the 100%-selective production of various conjugated aldehydes, including 4-anisaldehyde, cuminaldehyde, and the vitamin B6 derivative. By implementing a TiO2//Fe2O3 dual-photoanode system, we achieve an enhanced piperonal production rate of 31.2 µmol h-1 cm-2 at 1.0 V vs Ag/Ag+ and demonstrate its stability over a 102 h cyclic test, ensuring near-quantitative yield. This research illuminates the potential of the PEC strategy as a generally applicable method for the efficient production of high-value aldehydes.

Advancing nonlinear optics: discovery and characterization of new non-centrosymmetric phenazine-based halides.

Organic-inorganic metal halides (OIMHs) have drawn considerable attention due to their remarkable optoelectronic properties and substantial promise for nonlinear optical applications. In this research, phenazine has been selected as the organic cation because of its π-conjugated feature. Three compounds, (C12H9N2)PbCl3, (C12H9N2)SbCl4, and (C12H9N2)2InBr4·Br, were synthesized. Initial space group assignments were centrosymmetric for (C12H9N2)PbCl3 and (C12H9N2)SbCl4. However, under 1550 nm laser excitation, (C12H9N2)PbCl3 and (C12H9N2)SbCl4 exhibited second harmonic generation intensities ∼1.7 times greater than that of the benchmark KH2PO4. Structural reevaluation ultimately confirmed non-centrosymmetric P1 and P21 space groups for (C12H9N2)PbCl3 and (C12H9N2)SbCl4, respectively. Upon excitation at 335 nm and 470 nm, (C12H9N2)PbCl3, (C12H9N2)SbCl4, and (C12H9N2)2InBr4·Br emit fluorescence at room temperature. (C12H9N2)2InBr4·Br exhibits reversible phase transitions, showing potential for phase change energy storage. Our research underscores the critical role of comprehensive experimental validation in determining the precise crystallographic space groups and reveals the extensive potential of OIMHs as versatile candidates for advanced optoelectronic applications.

The trunk replaces the longer mandible as the main feeding organ in elephant evolution.

The long-trunked elephantids underwent a significant evolutionary stage characterized by an exceptionally elongated mandible. The initial elongation and subsequent regression of the long mandible, along with its co-evolution with the trunk, present an intriguing issue that remains incompletely understood. Through comparative functional and eco-morphological investigations, as well as feeding preference analysis, we reconstructed the feeding behavior of major groups of longirostrine elephantiforms. In the Platybelodon clade, the rapid evolutionary changes observed in the narial region, strongly correlated with mandible and tusk characteristics, suggest a crucial evolutionary transition where feeding function shifted from the mandible to the trunk, allowing proboscideans to expand their niches to more open regions. This functional shift further resulted in elephantids relying solely on their trunks for feeding. Our research provides insights into how unique environmental pressures shape the extreme evolution of organs, particularly in large mammals that developed various peculiar adaptations during the late Cenozoic global cooling trends.

The elephant's trunk is one of the most efficient food-gathering organs in the animal kingdom. From large branches to thin blades of grass, it can coil around and bring many types of vegetation to the animals' strong, short mandibles. This versatility allows elephants to thrive in a range of environments, including grasslands. Trunks are not the only spectacular feature to emerge in Proboscideans, the family of which elephants are the only surviving group. During the early and middle Miocene (between 23 to 11.6 million years ago), many of these species had dramatically elongated lower jaws; how and why this trait emerged then disappeared is poorly understood. The role that lengthened mandibles and trunks played during feeding also remains unclear. To address these questions, Li et al. focused on Platybelodon, Choerolophodon and Gomphotherium, which belong to three Proboscidean families that roamed Northern China between 17 and 15 million years ago. Each had elongated lower jaws, but with strikingly distinct lengths and morphologies. Chemical analyses on enamel samples helped determine which habitat the families occupied, while mathematical modelling revealed how their mandibles tackled different types of plants. Trunk shape was assessed via analyses of the nasal region. The results suggest that Choerolophodon had mandibles better suited for processing branches and a short, 'primitive' trunk. Gomphotherium sported a versatile jaw that could handle both grass and trees, as well as a rather 'elephant-like' trunk. The jaw of Platybelodon seemed well-adapted to cut grass, and remarkable bone structures point towards a long, strong and flexible trunk. While modern elephants fully depend on their trunks to eat, morphological constraints suggest that, in these species, the appendage only served to assist feeding (e.g., by pressing down on branches). All families shared an environment that included grasslands and forests, but analyses suggest that, for a period, Choerolophodon favored relatively closed habitats while Platybelodon spread into grasslands and Gomphotherium navigated both landscapes. This suggests that the evolution of long, strong and flexible trunks is tightly associated with grazing. About 14 million years ago, a global cooling event led to grasslands expanding worldwide. The fossil record shows the mandibles of Proboscideans starting to shorten after this period, including in the descendants of Gomphotherium that would give rise to modern elephants. The work by Li et al. sheds light onto these evolutionary processes, and the environmental pressures which helped shape the trunk.

The association of cardiometabolic multimorbidity and fear of falling among older adults: Data from the national health and aging trends study.

OBJECTIVES: Cardiometabolic diseases (CMDs) have been individually associated with fall-related outcomes, but their combined effect on fear of falling (FOF) has not been investigated. This study aims to examine the association between cardiometabolic multimorbidity and FOF in older adults. METHODS: Data from the National Health and Aging Trends Study, 4,295 community-dwelling older adults ≥ 65 years were analyzed in this longitudinal study. CMDs were assessed at baseline, including heart disease, diabetes, stroke, and hypertension. FOF was evaluated by asking participants if they worried about falling in the past month. Data were analyzed using multi-adjusted logistic regression. RESULTS: Cardiometabolic multimorbidity was associated with a higher risk of FOF. The combination of heart disease and diabetes showed the highest risk of FOF (OR = 3.47, 95 % CI: 1.63-7.40). CONCLUSIONS: These findings underscore the need for targeted interventions to mitigate the combined impact of cardiometabolic multimorbidity on FOF in older adults.

Review on the pharmacological effects and pharmacokinetics of scutellarein.

Scutellarein is a flavonoid from Scutellaria baicalensis Georgi that has been shown to have a variety of pharmacological activities. This review aims to summarize the pharmacological and pharmacokinetic studies on scutellarein and provide useful information for relevant scholars. Pharmacological studies indicate that scutellarein possesses a diverse range of pharmacological properties, including but not limited to anti-inflammatory, antioxidant, antiviral, neuroprotective, hypoglycemic, hypolipidemic, anticancer, and cardiovascular protective effects. Further investigation reveals that the pharmacological effects of scutellarein are driven by multiple mechanisms. These mechanisms encompass the scavenging of free radicals, inhibition of the activation of inflammatory signaling pathways and expression of inflammatory mediators, inhibition of the activity of crucial viral proteins, suppression of gluconeogenesis, amelioration of insulin resistance, improvement of cerebral ischemia-reperfusion injury, induction of apoptosis in cancer cells, and prevention of myocardial hypertrophy, among others. In summary, these pharmacological studies suggest that scutellarein holds promise for the treatment of various diseases. It is imperative to conduct clinical studies to further elucidate the therapeutic effects of scutellarein. However, it is worth noting that studies on the pharmacokinetics reveal an inhibitory effect of scutellarein on uridine 5'-diphosphate glucuronide transferases and cytochrome P450 enzymes, potentially posing safety risks.

Echinatin suppresses cutaneous squamous cell carcinoma by targeting GSTM3-mediated ferroptosis.

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is one of the most common skin cancers for which effective drugs are urgently needed. Echinatin, a natural compound extracted from Glycyrrhiza plants, has shown promising antitumour effects. However, the efficacy and the direct target of echinatin in cSCC remain unclear. PURPOSE: This study conducted a systematic investigation of the antitumour effects of echinatin on cSCC and the underlying mechanisms involved. STUDY DESIGN AND METHODS: Three cSCC cell lines, a xenograft model, and a UV-induced cSCC mouse model were used to investigate the potential protective effects of echinatin. The interactions between echinatin and glutathione S-transferase mu3 (GSTM3) and between echinatin and peroxiredoxin-2 (PRDX2) were evaluated by a proteome microarray assay, pull-down LC‒MS/MS analysis, surface plasmon resonance, and molecular docking. The potential mechanisms of GSTM3-mediated echinatin activity were analysed by using western blotting, lentivirus infection and small interfering RNA (siRNA) transfection. RESULTS: In this study, we found that echinatin inhibited the proliferation and migration of cSCC cells but had no cytotoxic effect on primary human keratinocytes. Furthermore, echinatin significantly inhibited tumour growth in vivo. Mechanistically, our data showed that echinatin could directly bind to GSTM3 and PRDX2. Notably, echinatin inhibited GSTM3 and PRDX2 levels by promoting their proteasomal degradation, which led to the disruption of ROS production. We then revealed that echinatin increased mitochondrial ROS production by inhibiting GSTM3. Moreover, echinatin triggered ferroptosis by inhibiting GSTM3-mediated ferroptosis negative regulation (FNR) proteins. In addition, echinatin regulated GSTM3-mediated ROS/MAPK signalling. CONCLUSION: Echinatin has good antitumour effects both in vitro and in vivo. Moreover, our findings indicate that GSTM3 and PRDX2 could function as viable targets of echinatin in cSCC. Consequently, echinatin represents a novel treatment for cSCC through the targeting of GSTM3-mediated ferroptosis.

Berberine ameliorates nonalcoholic fatty liver disease-induced bone loss by inhibiting ferroptosis.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) may contribute to osteoporosis. Berberine is a traditional Chinese medicine and was recently shown to be beneficial in NAFLD. However, little is known about its impact on bone loss induced by NAFLD. AIM: We aimed to explore the role of berberine in bone loss and determine its underlying mechanisms in NAFLD. METHODS: C57BL/6 mice were fed a high-fat high-fructose high-glucose diet (HFFGD) for 16 weeks to establish a NAFLD mouse model. The mice were administered berberine (300 mg/kg/d) by gavage, and fatty liver levels and bone loss indicators were tested. RESULTS: Berberine significantly improved HFFGD-induced weight gain, hepatic lipid accumulation and increases in serum liver enzymes, thereby alleviating NAFLD. Berberine increased trabecular number (Tb. N), trabecular thickness (Tb. Th), bone volume to tissue volume ratio (BV/TV), and decreased trabecular separation (Tb. Sp) and restored bone loss in NAFLD. Mechanistically, berberine significantly inhibited ferroptosis and 4-hydroxynonenal (4-HNE), prostaglandin-endoperoxide synthase 2 (PTGS2), and transferrin (TF) levels and increased ferritin heavy chain (FTH) levels in the femurs of HFFGD-fed mice. Moreover, berberine also activated the solute carrier family 7 member 11 (SLC7A11)/glutathione (GSH)/glutathione peroxidase 4 (GPX4) signaling pathway. CONCLUSION: Berberine significantly ameliorates bone loss induced by NAFLD by activating the SLC7A11/GSH/GPX4 signaling pathway and inhibiting ferroptosis. Therefore, berberine may serve as a therapeutic agent for NAFLD-induced bone loss.

Global research trends in immunotherapy for non-small cell lung cancer patients with KRAS mutations: a bibliometric analysis.

Background: Immunotherapy, frequently combined with conventional chemotherapy, is crucial for treating NSCLC. Kirsten rat sarcoma virus (KRAS) is a poor prognostic factor in patients with NSCLC, particularly lung adenocarcinoma, where binding of conventional inhibitors to mutated KRAS proteins is challenging. Field profiles, research hotspots, and prospects for immunotherapy for patients with NSCLC-carrying KRAS mutations were uncovered in this study. Methods: Microsoft Excel 2019, Bibliometrix, VOSviewer software, and Citespace were utilized to conduct a comprehensive scientometric analysis and understand a specific research field's knowledge base and frontiers aided by bibliometrics. Results: Between 2014 and 2023, 398 eligible documents in the English language were acquired using the WoSCC database, of which 113 and 285 were reviews and articles, respectively. The growth rate per year was 34.25 %. The most cited articles were from the United States, and China published the highest number of articles. Cancers was the journal, with increased publications in recent years. The keywords with the strongest citation bursts were analyzed using Citespace. "Immune checkpoint inhibitors," "co-occurring genomic alterations," and "KRAS" are among the research hotspots in this field. Conclusion: Using bibliometric and visual analyses, we examined immunotherapy for patients with KRAS-mutant NSCLC over the previous decade. The whole analysis showed a steady, quick increase in yearly publications in this area. Our findings will provide a roadmap for future research on the mechanisms of immunotherapy and immune checkpoint inhibitor action in treating KRAS-mutant NSCLC.

Sr2HgGe2OS6: A Hg-Based Oxychalcogenide Infrared Nonlinear Optical Material Exhibiting Favorable Balance between a Large Band Gap and Strong Second Harmonic Generation Response.

Currently, oxychalcogenides with mixed-anion groups that integrate the property advantages of oxides (wide optical band gap) and chalcogenides [strong second harmonic generation (SHG) response] through chemical substitution engineering have attracted widespread interest and are considered to be important candidates for infrared (IR) nonlinear optical (NLO) materials. Herein, the first Hg-based oxychalcogenide Sr2HgGe2OS6 with mixed anion [GeOS3] units has been successfully synthesized through a spontaneous crystallization method, which exhibits a favorable balance between the strong SHG response (0.7 × AgGaS2) and large optical band gap (2.9 eV). In addition, Sr2HgGe2OS6 shows high laser-induced damage threshold (LIDT, 2.1 × AgGaS2) as well as phase-matching (PM) performance. Theoretical calculations indicate that the Sr2HgGe2OS6 encompasses large birefringence of 0.128@2090 nm (3.3 × AgGaS2) and its SHG density mainly comes from [HgS4] tetrahedra and [GeOS3] units. This work not only demonstrates that Sr2HgGe2OS6 is a promising IR NLO material but also provides new ideas for the exploration of Hg-based oxychalcogenide IR NLO materials.