Identifying optimal surgical approach among T1N2-3M0 non-small cell lung cancer patients: a population-based analysis.

Background: Whether stage T1N2-3M0 non-small cell lung cancer (NSCLC) patients could benefit from surgery and the optimal surgical procedure have remained controversial and unclear. This study aimed to investigate whether stage T1N2-3M0 NSCLC can benefit from different surgery types and develop a tool for survival prediction. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify patients diagnosed with stage T1N2-3M0 NSCLC between 2000 and 2015. A 1:1 propensity score-matched (PSM) analysis was used to balance the distribution of clinical characteristics. Survival analyses were performed by using the Kaplan-Meier (KM) curves and Cox proportional hazards regression. All patients were randomly split at a ratio of 7:3 into training and validation cohorts. The nomogram was constructed by integrating all independent predictors for overall survival (OS) and cancer-specific survival (CSS). The model's performance was evaluated by discrimination, calibration ability, and risk stratification ability. Results: A total of 4,671 patients were enrolled. After 1:1 PSM, the distribution proportions of clinical characteristics in 1,146 patients were balanced (all P>0.05). The non-surgical approach was associated with worse survival compared with sublobectomy and lobectomy in the unmatched and matched cohorts. The multivariate Cox analysis showed that sublobectomy and lobectomy were both related to better OS and CSS rates compared with no surgery (P<0.001). Moreover, the results of subgroup analyses based on age, N stage, and radiotherapy or chemotherapy strategy were consistent. A total of 801 patients were included in the training cohort and 345 cases constituted the validation cohort. The nomogram constructed for the 1-, 3-, and 5-year OS and CSS prediction showed good discrimination, performance, and calibration both in the training and validation sets. Significant distinctions in survival curves between different risk groups stratified by prognostic scores were also observed (all P<0.001). Conclusions: Stage T1N2-3M0 NSCLC patients could benefit from sublobectomy or lobectomy, and lobectomy provides better survival benefits. We developed and validated nomograms, which could offer clinicians instructions for strategy making.

CircNCX1 modulates cardiomyocyte proliferation through promoting ubiquitination of BRG1.

In mammal, the myocardium loss cannot be recovered spontaneously due to the negligible proliferation ability of mature mammalian cardiomyocyte. However, accumulated evidence has shown that terminally differentiated mammalian cardiomyocyte also has proliferation potency, which can be mediated by several mechanisms. Here, we reported that circNCX1, the most abundant circular RNA in mammalian hearts, can affect the proliferation of murine cardiomyocytes. The level of circNCX1 is significantly elevated during heart development. Forced expression of circNCX1 inhibits cardiomyocyte proliferation, while silencing of endogenous circNCX1 in cardiomyocyte shows reversed effect in vitro. Mechanistically, circNCX1 functions via negatively regulating transcription activator BRG1. It bridges BRG1 and FBXW7 to enhance the ubiquitination and degradation of BRG1, decreasing the expression of BMP10 to lead cell cycle arrest. In summary, our study first revealed that circNCX1 is a modulator of cardiomyocyte proliferation.

Excited-state Engineering Enables Efficient Deep-blue Light-emitting Diodes Exhibiting BT.2020 Color Gamut.

Organic luminescent materials that exhibit thermally activated delayed fluorescence (TADF) can convert non-emissive triplet excitons into emissive singlet states through a reverse intersystem crossing (RISC) process. Therefore, they have tremendous potential for applications in organic light-emitting diodes (OLEDs). However, with the development of ultra-high definition 4K/8K display technologies, designing efficient deep-blue TADF materials to achieve the Commission Internationale de l'Éclairage (CIE) coordinates fulfilling BT.2020 remains a significant challenge. Here, we propose an effective approach to design deep-blue TADF molecules based on hybrid long- and short-range charge-transfer by incorporation of multiple donor moieties into organoboron multiple resonance acceptors. The resulting TADF molecule exhibits deep-blue emission at 414 nm with a full width at half maximum (FWHM) of 29 nm, together with a thousand-fold increase in RISC rate. OLEDs based on our champion material achieved a record maximum external quantum efficiency (EQE) of 22.8% with CIE coordinates of (0.163, 0.046), approaching the coordinates of the BT.2020 blue standard. Moreover, TADF-assisted fluorescence devices employing our designed material as a sensitizer exhibited an exceptional EQE of 33.1%. Our work thus provides a blueprint for future development of efficient deep-blue TADF emitters, representing an important milestone towards meeting the blue color gamut standard of BT.2020. This article is protected by copyright. All rights reserved.

[Chemical Speciation, Influencing Factors, and Regression Model of Heavy Metals in Farmland of Typical Carbonate Area with High Geological Background, Southwest China].

The speciation of heavy metals in soil is an important factor determining their bioavailability and toxicity, and it is crucial for the scientific assessment of ecological risks posed by heavy metals in soils of typical carbonate areas with high geological background in southwest China. In order to investigate the distribution of speciation of heavy metals in soils of carbonate rock with high geological background, we selected a typical carbonate rock distribution area in Guizhou Province and used the second national soil survey plots as sampling units. A total of 309 topsoil samples were collected from farmland. The improved Tessier seven-step sequential extraction method was used to analyze the seven chemical forms of heavy metals:water-soluble (F1); exchangeable (F2); carbonate-bound (F3); weakly organic-bound (F4); iron-manganese oxide-bound (F5); strongly organic-bound (F6); and residual (F7) forms of arsenic (As), cadmium (Cd), copper (Cu), mercury (Hg), nickel (Ni), lead (Pb), and zinc (Zn). The study found that the residual forms of heavy metals As, Cu, Hg, Ni, Pb, and Zn in the soil accounted for more than 50%, the effective components (F1-F3) accounted for less than 5%, and the potential biological effective components (F4-F6) were less than 45%, indicating low reactivity and low ecological risk. The effective and potentially bioavailable components of Cd accounted for 55.49% and 29.37%, respectively, which were much higher than those of other heavy metals. The ecological risk based on the speciation of heavy metals in the soil was much lower than that based on the total content of heavy metals. The stepwise regression equations could effectively establish the relationship between the bioavailable and potentially bioavailable fractions of Cd, Cu, and Pb and their influencing factors. Total heavy metal contents and pH value were important factors influencing the speciation of heavy metals in soils of carbonate rock with high geological background areas. The enrichment of heavy metal elements in the residual fraction was influenced by long-term zinc smelting activities and the weathering of carbonate rocks into soil. Soil organic matter (OM) and oxide content had a relatively small influence on the speciation of heavy metals in the soil.

Reproductive factors and risk of cardiovascular diseases and all-cause and cardiovascular mortality in American women: NHANES 2003-2018.

BACKGROUND: The evidence regarding the association of reproductive factors with cardiovascular diseases (CVDs) is limited. AIMS: To investigate the relationship of reproductive factors with the risk of CVDs, as well as all-cause and cardiovascular mortality. METHODS: This study included 16,404 adults with reproductive factors from the National Health and Nutrition Examination Survey (NHANES) and followed up until 31 December 2019. Logistic models and restricted cubic spline models were used to assess the association of reproductive factors with CVDs. COX proportional hazards models and restricted cubic spline models, with adjustment for potential confounding, were employed to analyze the relation between reproductive factors and cardiovascular and all-cause death. RESULTS: There is a nonlinear relationship between age at menarche and CVDs. Age at menopause ≤ 11(OR 1.36, 95% CI 1.10-1.69) was associated with an increased risk of CVDs compared to ages 12-13 years. Age at Menopause ≤ 44 (OR 1.69, 95% CI 1.40-2.03) was associated with increased CVDs compared to age 35-49 years. Number of pregnancies ≥ 5(OR 1.26, 95% CI 1.02-1.55) was associated with an increased risk of CVDs compared to one pregnancy. In continuous variable COX regression models, a later age at menopause (HR 0.98, 95% CI 0.97-0.99) and a longer reproductive lifespan (HR 0.98, 95% CI 0.97-0.99) were associated with a decreased risk of all-cause death. A later age at menopause (HR 0.98, 95% CI 0.97-0.99) and a longer reproductive lifespan (HR 0.98, 95% CI 0.97-0.99) were associated with a decreased risk of cardiac death. CONCLUSIONS: Female reproductive factors are significant risk factors for CVDs American women.

A guide to troubleshooting metal sacrificial anodes for organic electrosynthesis.

The development of reductive electrosynthetic reactions is often enabled by the oxidation of a sacrificial metal anode, which charge-balances the reductive reaction of interest occurring at the cathode. The metal oxidation is frequently assumed to be straightforward and innocent relative to the chemistry of interest, but several processes can interfere with ideal sacrificial anode behavior, thereby limiting the success of reductive electrosynthetic reactions. These issues are compounded by a lack of reported observations and characterization of the anodes themselves, even when a failure at the anode is observed. Here, we weave lessons from electrochemistry, interfacial characterization, and organic synthesis to share strategies for overcoming issues related to sacrificial anodes in electrosynthesis. We highlight common but underexplored challenges with sacrificial anodes that cause reactions to fail, including detrimental side reactions between the anode or its cations and the components of the organic reaction, passivation of the anode surface by an insulating native surface film, accumulation of insulating byproducts at the anode surface during the reaction, and competitive reduction of sacrificial metal cations at the cathode. For each case, we propose experiments to diagnose and characterize the anode and explore troubleshooting strategies to overcome the challenge. We conclude by highlighting open questions in the field of sacrificial-anode-driven electrosynthesis and by indicating alternatives to traditional sacrificial anodes that could streamline reaction optimization.

Temperature modulated sustainable on/off photosynthesis switching of microalgae towards hydrogen evolution.

Despite great progress in the active interfacing between various abiotic materials and living organisms, the development of a smart polymer matrix with modulated functionality of algae towards the application of green bioenergy is still rare. Herein, we design a thermally sensitive poly(N-isopropylacrylamide)-co-poly(butyl acrylate) with an LCST (ca. 25 °C) as a chassis, which could co-assemble with algal cells based on hydrophobic interaction to generate a new type of robust hybrid hydrogel living material. By modulating the temperature to 30 °C, the volume of the polymer matrix is shrunk by 9 times, which allows the formation of physical shading and metabolism changing of the algae, and then triggers the functionality switching of the algae from photosynthetic oxygen production to hydrogen production. By contrast, by decreasing the temperature to 20 °C, the hybrid living materials go into a sol state where the algae behave normally with photosynthetic oxygen production. In particular, due to the proliferation of the algae in living materials, a long-term and exponential enhancement in the amount of hydrogen produced is achieved. Overall, it is anticipated that our investigations could provide a new paradigm for the development of polymer/living organism-based hybrid living materials with synergistic functionality boosting green biomanufacturing.

Extracellular ATP is a homeostatic messenger that mediates cell‒cell communication in physiological processes and psychiatric diseases.

Neuronal activity is the basis of information encoding and processing in the brain. During neuronal activation, intracellular ATP is generated to meet the high-energy demands. Meantime, ATP is secreted, increasing the extracellular ATP concentration and acting as a homeostatic messenger that mediates cell‒cell communication to prevent aberrant hyperexcitability of the nervous system. In addition to the confined release and fast synaptic signaling of classic neurotransmitters within synaptic clefts, ATP can be released by all brain cells, diffuses widely and targets different types of purinergic receptors on neurons and glial cells, making it possible to orchestrate brain neuronal activity and participate in various physiological aspects, such as sleep and wakefulness, learning and memory, and feeding. Dysregulation of extracellular ATP leads to a "destabilizing" effect on the neural network, as found in the etiopathology of many psychiatric diseases, including depression, anxiety, schizophrenia, and autism spectrum disorder. This review summarizes advances in the understanding of the mechanisms by which extracellular ATP serves as an intercellular signaling molecule to regulate neural activity, with a focus on how it maintains the homeostasis of neural networks. In particular, we also focus on neural activity issues resulting from dysregulation of extracellular ATP and propose that aberrant levels of extracellular ATP may play a role in the etiopathology of some psychiatric diseases, highlighting the potential therapeutic targets of ATP signaling in the treatment of these psychiatric diseases. Finally, we suggest potential avenues to further elucidate the role of extracellular ATP in intercellular communication and psychiatric diseases.

Physiological Regulation of Photosynthetic-Related Indices, Antioxidant Defense, and Proline Anabolism on Drought Tolerance of Wild Soybean (Glycine soja L.).

Wild soybean (Glycine soja L.), drought-tolerant cultivar Tiefeng 31 (Glycine max L.), and drought-sensitive cultivar Fendou 93 (Glycine max L.) were used as materials to investigate the drought tolerance mechanism after 72 h 2.5 M PEG 8000 (osmotic potential -0.54 MPa)-simulated drought stress at the seedling stage. The results indicated that the leaves of the G. soja did not wilt under drought stress. However, both the drought-tolerant and drought-sensitive cultivated soybean cultivars experienced varying degrees of leaf wilt. Notably, the drought-sensitive cultivated soybean cultivars exhibited severe leaf wilt after the drought stress. Drought stress was determined to have a significant impact on the dry matter of the above-ground part of the drought-sensitive cultivar Fendou 93, followed by the drought-tolerant cultivar Tiefeng 31, with the lowest reduction observed in G. soja. Furthermore, the presence of drought stress resulted in the closure of leaf stomata. G. soja exhibited the highest proportion of stomatal opening per unit area, followed by the drought-tolerant cultivar Tiefeng 31, while the drought-sensitive cultivar Fendou 93 displayed the lowest percentage. Photosynthesis-related indexes, including photosynthetic rate, intercellular CO2, transpiration rate, and stomatal conductance, decreased in Fendou 93 and Tiefeng 31 after drought stress, but increased in G. soja. In terms of the antioxidant scavenging system, lower accumulation of malondialdehyde (MDA) was observed in G. soja and Tiefeng 31, along with higher activities of superoxide dismutase (SOD, EC 1.15.1.1) and catalase (CAT, EC 1.11.1.6) to counteract excess reactive oxygen species and maintain cell membrane integrity. In contrast, the drought-sensitive cultivar Fendou 93 had higher MDA content and higher activities of ascorbate peroxidase (APX, EC 1.11.1.11) and peroxidase (POD, 1.11.1.7). G. soja and Tiefeng 31 also exhibited less accumulation of osmolytes, including soluble sugar, soluble protein, and free proline content. The activities of δ-OAT, ProDH, and P5CS, key enzymes in proline anabolism, showed an initial increase under drought stress, followed by a decrease, and then an increase again at the end of drought stress in G. soja. Before drought stress, Tiefeng 31 had higher activities of ProDH and P5CS, which decreased with prolonged drought stress. Fendou 93 experienced an increase in the activities of δ-OAT, ProDH, and P5CS under drought stress. The δ-OAT gene expression levels were up-regulated in all three germplasms. The expression levels of the P5CS gene in Fendou 93 and Tiefeng 31 were down-regulated, while G. soja showed no significant change. The expression of the P5CR gene and ProDH gene was down-regulated in Fendou 93 and Tiefeng 31, but up-regulated in G. soja. This indicates that proline content is regulated at both the transcription and translation levels.

A young woman with Mycobacterium chelonae complex infection caused by facial stem cell injection.

In outpatient settings, Mycobacterium chelonae complex infection brought on by cosmetic injections are rather uncommon. We came across a case of infection brought on by a commercial stem cell injection.

Multimodal phototherapy agents target lipid droplets for near-infrared imaging-guided type I photodynamic/photothermal therapy.

The construction and optimization of a single phototherapeutic agent with photoluminescence, type I photodynamic therapy (PDT), and photothermal therapy (PTT) functions remain challenging. In this study, we aimed to design and synthesize four donor-acceptor (D-A) type aggregation-induced emission molecules: PSI, TPSI, PSSI, and TPSSI. We employed phenothiazine as an electron donor and 1,3-bis(dicyanomethylidene)indan as a strong electron acceptor in the synthesis process. Among them, TPSSI exhibited efficient type I reactive oxygen species generation, high photothermal conversion efficiency (45.44 %), and near-infrared emission. These observations can be attributed to the introduction of a triphenylamine electron donor group and a thiophene unit, which resulted in increased D-A strengths, a reduced singlet-triplet energy gap, and increased free intramolecular motion. TPSSI was loaded into bovine serum albumin to prepare biocompatible TPSSI nanoparticles (NPs). Our results have indicated that TPSSI NPs can target lipid droplets with negligible dark toxicity and can efficiently generate O2•- in hypoxic tumor environments. Moreover, TPSSI NPs selectively targeted 4T1 tumor tissues and exhibited a good PDT-PTT synergistic effect in vitro and in vivo. We believe that the successful preparation of multifunctional phototherapeutic agents will promote the development of efficient tumor diagnosis and treatment technologies. STATEMENT OF SIGNIFICANCE: The construction of a single phototherapeutic agent with photoluminescence, type I photodynamic therapy, and photothermal therapy functions, and its optimization remain challenging. In this study, we construct four donor-acceptor aggregation-induced emission molecules using phenothiazine as an electron donor and 1,3-Bis(dicyanomethylidene)indan as a strong electron acceptor. By optimizing the molecular structure, an integrated phototherapy agent with fluorescence imaging ability and high photodynamic / photothermal therapy performance was prepared. We believe that the successful preparation of multifunctional phototherapeutic agents will promote the development of efficient tumor diagnosis and treatment technology.

Gastric mechanosensitive channel Piezo1 regulates ghrelin production and food intake.

Ghrelin, produced mainly by gastric X/A-like cells, triggers a hunger signal to the central nervous system to stimulate appetite. It remains unclear whether X/A-like cells sense gastric distention and thus regulate ghrelin production. Here we show that PIEZO1 expression in X/A-like cells decreases in patients with obesity when compared to controls, whereas it increases after sleeve gastrectomy. Male and female mice with specific loss of Piezo1 in X/A-like cells exhibit hyperghrelinaemia and hyperphagia and are more susceptible to overweight. These phenotypes are associated with impairment of the gastric CaMKKII/CaMKIV-mTOR signalling pathway. Activation of PIEZO1 by Yoda1 or gastric bead implantation inhibits ghrelin production, decreases energy intake and induces weight loss in mice. Inhibition of ghrelin production by Piezo1 through the CaMKKII/CaMKIV-mTOR pathway can be recapitulated in a ghrelin-producing cell line mHypoE-42. Our study reveals a mechanical regulation of ghrelin production and appetite by PIEZO1 of X/A-like cells, which suggests a promising target for anti-obesity therapy.

The rapid proximity labeling system PhastID identifies ATP6AP1 as an unconventional GEF for Rheb.

Rheb is a small G protein that functions as the direct activator of the mechanistic target of rapamycin complex 1 (mTORC1) to coordinate signaling cascades in response to nutrients and growth factors. Despite extensive studies, the guanine nucleotide exchange factor (GEF) that directly activates Rheb remains unclear, at least in part due to the dynamic and transient nature of protein-protein interactions (PPIs) that are the hallmarks of signal transduction. Here, we report the development of a rapid and robust proximity labeling system named Pyrococcus horikoshii biotin protein ligase (PhBPL)-assisted biotin identification (PhastID) and detail the insulin-stimulated changes in Rheb-proximity protein networks that were identified using PhastID. In particular, we found that the lysosomal V-ATPase subunit ATP6AP1 could dynamically interact with Rheb. ATP6AP1 could directly bind to Rheb through its last 12 amino acids and utilizes a tri-aspartate motif in its highly conserved C-tail to enhance Rheb GTP loading. In fact, targeting the ATP6AP1 C-tail could block Rheb activation and inhibit cancer cell proliferation and migration. Our findings highlight the versatility of PhastID in mapping transient PPIs in live cells, reveal ATP6AP1's role as an unconventional GEF for Rheb, and underscore the importance of ATP6AP1 in integrating mTORC1 activation signals through Rheb, filling in the missing link in Rheb/mTORC1 activation.

Omega-3 Fatty Acids for Depression in the Elderly and Patients with Dementia: A Systematic Review and Meta-Analysis.

This study aimed to evaluate the efficacy of omega-3 fatty acid supplementation interventions in improving depression in patients with dementia. To achieve this objective, randomized controlled trials (RCTs) were identified from primary electronic databases, focusing on the relationship between omega-3 fatty acids and depression in patients with dementia. The primary outcome was the impact of omega-3 fatty acids on post-intervention depression in patients with dementia, with subgroup analyses conducted based on the type of intervention (docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) combination), duration of intervention (3 months, 6 months, 12 months, ≥24 months), cognitive function (ranging from mild cognitive impairment (MCI) to severe dementia), and daily dosage (high, medium, low, applicable to both DHA and EPA). The study has been duly registered with PROSPERO (registration ID: CRD42023408744). A meta-analysis of five studies (n = 517) included in nine systematic reviews showed that omega-3 supplementation had a non-significant trend toward affecting depressive symptoms in patients with dementia (standardized mean difference (SMD): 0.147; 95% confidence interval (CI): -0.324 to 0.049; p = 0.141). Subgroup analyses revealed that DHA supplementation significantly reduced depressive symptoms (SMD: -0.247; p = 0.039). There was no significant effect for high (SMD: -0.169; 95% CI: -0.454 to 0.116; p = 0.246) or medium (SMD: -0.061; 95% CI: -0.228 to 0.105; p = 0.470) doses of EPA. However, low doses of EPA were significantly effective (SMD: -0.953; 95% CI: -1.534 to -0.373; p = 0.001), with notable improvements in patients with MCI (SMD: -0.934; p < 0.001). The study concludes that omega-3 fatty acids, particularly through DHA supplementation, may alleviate depressive symptoms in patients with MCI. Given the limited sample size, further long-term RCTs are recommended to better understand the efficacy and optimal management of omega-3 supplementation in this population using different dosages.

Elevated dorsal medial prefrontal cortex to lateral habenula pathway activity mediates chronic stress-induced depressive and anxiety-like behaviors.

The medial prefrontal cortex (mPFC) sends projections to numerous brain regions and is believed to play a significant role in depression and anxiety. One of the key downstream targets of the mPFC, the lateral habenula (LHb), is essential for chronic stress (CS)-induced depressive and anxiety-like behaviors. Nevertheless, whether the mPFC-LHb pathway mediates the co-occurrence of depression and anxiety and the underlying mechanism remain incompletely understood. Here, using chemogenetics, we first determined that activation of LHb-projecting mPFC neurons is essential for the development of depressive and anxiety-like behaviors induced by CS. Subsequently, we identify the extent and distribution of LHb-projecting neurons originating from the mPFC subregion. Through circuit-specific in vivo fiber photometry, we found that Ca2+ activity in dorsal mPFC (dmPFC) axon terminals within the LHb was increased during exposure to stressful and anxiety-related stimuli, highlighting the potential role of LHb-projecting dmPFC neurons in conveying stressful and anxiety-related information to the LHb. Finally, we observed that activation of both LHb-projecting dmPFC neurons and their postsynaptic counterparts in the LHb was necessary for CS-induced depressive and anxiety-like behaviors. Overall, this study provides multiple lines of evidence demonstrating that activation of the dmPFC-LHb pathway is a crucial neural circuitry for CS-induced depressive and anxiety-like behaviors.

Optimization of lipid assisted polymeric nanoparticles for siRNA delivery and cancer immunotherapy.

To date, five siRNA-based medications have received clinical approval and have demonstrated remarkable therapeutic efficacy in treating various diseases. However, their application has been predominantly limited to liver-specific diseases due to constraints in siRNA delivery capabilities. In this study, we have developed a siRNA delivery system utilizing clinically approved mPEG-b-PLGA, a cationic lipid, and an ionizable lipid. We optimized this system by carefully adjusting their mass ratios, resulting in highly efficient gene silencing. Furthermore, the optimized nanoparticle formulation, which encapsulates siRNA targeting CD47, induces a robust immune response. This response effectively suppresses the progression of melanoma tumors by blocking this critical immune checkpoint.

Oxidized cellulose-filled double thermo/pH-sensitive hydrogel for local chemo-photothermal therapy in breast cancer.

Lumpectomy plus radiation is a treatment option offering better survival than conventional mastectomy for patients with early-stage breast cancer. However, successive radioactive therapy remains tedious and unsafe with severe adverse reactions and secondary injury. Herein, a composite hydrogel with pH- and photothermal double-sensitive activity is developed via physical crosslinking. The composite hydrogel incorporated with tempo-oxidized cellulose nanofiber (TOCN), polyvinyl alcohol (PVA) and a polydopamine (PDA) coating for photothermal therapy (PTT) triggered in situ release of doxorubicin (DOX) drug was utilized to optimize postoperative strategies of malignant tumors inhibition. The incorporation of TOCN significantly affects the performance of composite hydrogels. The best-performing TOCN/PVA7 was selected for drug loading and polydopamine coating by rational design. In vitro studies have demonstrated that the composite hydrogel exhibited high NIR photothermal conversion efficiency, benign cytotoxicity to L929 cells, pH-dependent release profiles, and strong MCF-7 cell inhibitory effects. Then the TOCN/PVA7-PDA@DOX hydrogel is implanted into the tumor resection cavity for local in vivo chemo-photothermal synergistical therapy to ablate residue tumor tissues. Overall, this work suggests that such a chemo-photothermal hydrogel delivery system has great potential as a promising tool for the postsurgical management of breast cancer.

Association between alcohol consumption and latent fasting blood glucose trajectories among midlife women.

Background: This investigation sought to elucidate the correlations between alcohol intake and trajectories of fasting blood glucose (FBG) among American women in midlife. Methods: Our analysis was rooted in the foundational data from the Study of Women's Health Across the Nation (SWAN), a comprehensive longitudinal study centered on US women during their midlife transition. We employed group-based trajectory modeling to chart the FBG trajectories spanning from 1996 to 2005. Employing logistic regression, we gauged the odds ratios (ORs) and 95% confidence intervals (CIs) to draw connections between initial alcohol consumption and FBG trajectory patterns, whilst controlling for predominant potential confounders. Results: Our cohort comprised 2,578 women in midlife, ranging in age from 42 to 52, each having a minimum of three subsequent FPG assessments. We discerned two distinct FBG trajectories: a low-stable pattern (n = 2,467) and a high-decreasing pattern (n = 111). Contrasted with the low-stable group, our data showcased an inverse relationship between alcohol intake and the high-decreasing FBG trajectory in the fully adjusted model 3. The most pronounced reduction was evident in the highest tertile of daily servings of alcoholic beverages (OR: 0.23, 95% CI: 0.10-0.52, p < 0.001), percentage of kilocalories sourced from alcoholic beverages (OR: 0.30, 95% CI: 0.16-0.58, p < 0.001), and daily caloric intake from alcoholic beverages (OR: 0.31, 95% CI: 0.16-0.62, p < 0.001). Conclusion: Moderate alcohol consumption may protect against high FPG trajectories in middle-aged women in a dose-response manner. Further researches are needed to investigate this causality in midlife women.

Glioblastoma patients' survival and its relevant risk factors during the pre-COVID-19 and post-COVID-19 pandemic: real-world cohort study in the USA and China.

BACKGROUND: Although the COVID-19 pandemic has exerted potential impact on patients with glioblastomas (GBMs), it remains unclear whether the survival and its related risk factors of GBM patients would be altered or not during the period spanning from pre-COVID-19 to post-COVID-19 pandemic era. This study aimed to clarify the important issues above. METHODS: Two observational cohorts were utilized, including the nationwide American cohort from the Surveillance, Epidemiology, and End-Results (SEER) and the Chinese glioblastoma cohort (CGC) at our institution during 2018-2020. Demographics, tumour features, treatment regimens and clinical outcomes were collected. Cox regression model, competing risk model, and subgroup and sensitivity analysis were used to dynamically estimate the survival and its relevant risk factors over different diagnosis years from the pre-COVID-19 (2018 and 2019) to post-COVID-19 (2020) pandemic. Causal mediation analysis was further adopted to explore the potential relationship between risk factors and mortality. RESULTS: This study included 11321 GBM cases in SEER and 226 GBM patients in CGC, respectively. Instead of the diagnostic years of 2018-2020, the prognostic risk factors, such as advanced age, bilateral tumour and absence of comprehensive therapy (surgery combined with chemoradiotherapy), were identified to persistently affect GBM survival independently during the period from 2018 to 2020 in the SEER cohort (all P < 0.05). In CGC, lack of comprehensive therapy for GBM patients were restated as survival risk factors during the same timeframe. Causal mediation analysis showed that the effect of comprehensive therapy on all-cause mortality played a determinant role (direct effect value -0.227, 95% CI -0.248 to -0.207), which was partially mediated by age (9.11%) rather than tumour laterality. CONCLUSIONS: As the timeframe shifted from pre-COVID-19 to post-COVID-19 pandemic, survival of GBM patients remained stable, yet advanced age, bilateral tumours, and passive treatment continuingly impacted GBM survival. It is necessary to optimize the comprehensive treatment for GBM patients even in the post-pandemic era.

Triphenylphosphonium-linked derivative of hecogenin with enhanced antiproliferative activity: Design, synthesis, and biological evaluation.

Hecogenin (HCG), a steroidal sapogenin, possesses good antitumor properties. However, the application of HCG for cancer treatment has been hindered primarily by its moderate potency. In this study, we incorporated triphenylphosphonium cation (TPP+) at the C-3 and C-12 positions through different lengths of alkyl chains to target mitochondria and enhance the efficacy and selectivity of the parent compound. Cytotoxicity screening revealed that most of the target compounds exhibited potent antiproliferative activity against five human cancer cell lines (MKN45, A549, HCT-116, MCF-7, and HepG2). Structure-activity relationship studies indicated that the TPP+ group significantly enhanced the antiproliferative potency of HCG. Among these compounds, 3c demonstrated remarkable potency against MKN45 cells with an IC50 value of 0.48 µM, significantly more effective than its parent compound HCG (IC50 > 100 µM). Further investigations into the mechanism of action revealed that 3c induced apoptosis of MKN45 cells through the mitochondrial pathway. In a zebrafish xenograft model, 3c inhibited the proliferation of MKN45 cells. Overall, these results suggest that 3c, with potent antiproliferative activity, may serve as a valuable scaffold for developing new antitumor agents.